Porter, Stephanie
2002-08-01
To provide an update for nurses involved in the care of women at risk or being treated for endometrial cancer. Review articles, research reports, and medical and nursing text-books. Endometrial cancer is the most common gynecologic malignancy. Although most women with endometrial cancer present with early stage disease and have an excellent chance of cure, approximately 6,600 women in the United States are expected to die from the disease in 2002. Treatment of patients with advanced or recurrent disease remains challenging, with no proven best standard of treatment. Nursing plays an important role in prevention and early detection of endometrial cancer, patient education, patient care, and rehabilitation.
... thick and show changes that look like cancer. Abnormal uterine bleeding is a common sign of EIN. Diagnosis and ... The most common symptom of endometrial cancer is abnormal uterine bleeding. For women who are premenopausal, this includes irregular ...
Role of emmprin in endometrial cancer
Directory of Open Access Journals (Sweden)
Nakamura Keiichiro
2012-05-01
Full Text Available Abstract Background Extracellular matrix metalloproteinase inducer (Emmprin/CD147 is a transmembrane glycoprotein that belongs to the immunoglobulin superfamily. Enriched on the surface of many tumor cells, emmprin promotes tumor growth, invasion, metastasis and angiogenesis. We evaluated the clinical importance of emmprin and investigated its role in endometrial cancer. Methods Emmprin expression was examined in uterine normal endometrium, endometrial hyperplasia and cancer specimens by immunohistochemistry. In addition, the biological functions and inhibitory effects of an emmprin knockdown were investigated in HEC-50B and KLE endometrial cancer cell lines. Results The levels of emmprin expression were significantly increased in the endometrial cancer specimens compared with the normal endometrium and endometrial hyperplasia specimens (p p p Conclusions The present findings suggest that low emmprin expression might be a predictor of favorable prognosis in endometrial cancer patients, and that emmprin may represent a potential therapeutic target for endometrial cancer.
Role of emmprin in endometrial cancer.
Nakamura, Keiichiro; Kodama, Junichi; Hongo, Atsushi; Hiramatsu, Yuji
2012-05-28
Extracellular matrix metalloproteinase inducer (Emmprin/CD147) is a transmembrane glycoprotein that belongs to the immunoglobulin superfamily. Enriched on the surface of many tumor cells, emmprin promotes tumor growth, invasion, metastasis and angiogenesis. We evaluated the clinical importance of emmprin and investigated its role in endometrial cancer. Emmprin expression was examined in uterine normal endometrium, endometrial hyperplasia and cancer specimens by immunohistochemistry. In addition, the biological functions and inhibitory effects of an emmprin knockdown were investigated in HEC-50B and KLE endometrial cancer cell lines. The levels of emmprin expression were significantly increased in the endometrial cancer specimens compared with the normal endometrium and endometrial hyperplasia specimens (p emmprin expression were significantly higher than those of patients with low emmprin expression (DFS: p Emmprin knockdown by the siRNA led to cell proliferation, migration and invasion through TGF-β, EGF, NF-κB, VEGF, MMP-2, and MMP-9 expression, which in turn resulted in increased levels of E-cadherin and reduced levels of Vimentin and Snail in endometrial cancer. The present findings suggest that low emmprin expression might be a predictor of favorable prognosis in endometrial cancer patients, and that emmprin may represent a potential therapeutic target for endometrial cancer.
Risks of Endometrial Cancer Screening
... Health history and certain medicines can affect the risk of developing endometrial cancer. Anything that increases your ... have abnormal vaginal bleeding, check with your doctor. Risks of Endometrial Cancer Screening Key Points Screening tests ...
DJ-1 is a reliable serum biomarker for discriminating high-risk endometrial cancer.
Di Cello, Annalisa; Di Sanzo, Maddalena; Perrone, Francesca Marta; Santamaria, Gianluca; Rania, Erika; Angotti, Elvira; Venturella, Roberta; Mancuso, Serafina; Zullo, Fulvio; Cuda, Giovanni; Costanzo, Francesco
2017-06-01
New reliable approaches to stratify patients with endometrial cancer into risk categories are highly needed. We have recently demonstrated that DJ-1 is overexpressed in endometrial cancer, showing significantly higher levels both in serum and tissue of patients with high-risk endometrial cancer compared with low-risk endometrial cancer. In this experimental study, we further extended our observation, evaluating the role of DJ-1 as an accurate serum biomarker for high-risk endometrial cancer. A total of 101 endometrial cancer patients and 44 healthy subjects were prospectively recruited. DJ-1 serum levels were evaluated comparing cases and controls and, among endometrial cancer patients, between high- and low-risk patients. The results demonstrate that DJ-1 levels are significantly higher in cases versus controls and in high- versus low-risk patients. The receiver operating characteristic curve analysis shows that DJ-1 has a very good diagnostic accuracy in discriminating endometrial cancer patients versus controls and an excellent accuracy in distinguishing, among endometrial cancer patients, low- from high-risk cases. DJ-1 sensitivity and specificity are the highest when high- and low-risk patients are compared, reaching the value of 95% and 99%, respectively. Moreover, DJ-1 serum levels seem to be correlated with worsening of the endometrial cancer grade and histotype, making it a reliable tool in the preoperative decision-making process.
Genetics of Endometrial Cancers
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Tsuyoshi Okuda
2010-01-01
Full Text Available Endometrial cancers exhibit a different mechanism of tumorigenesis and progression depending on histopathological and clinical types. The most frequently altered gene in estrogen-dependent endometrioid endometrial carcinoma tumors is PTEN. Microsatellite instability is another important genetic event in this type of tumor. In contrast, p53 mutations or Her2/neu overexpression are more frequent in non-endometrioid tumors. On the other hand, it is possible that the clear cell type may arise from a unique pathway which appears similar to the ovarian clear cell carcinoma. K-ras mutations are detected in approximately 15%–30% of endometrioid carcinomas, are unrelated to the existence of endometrial hyperplasia. A β-catenin mutation was detected in about 20% of endometrioid carcinomas, but is rare in serous carcinoma. Telomere shortening is another important type of genomic instability observed in endometrial cancer. Only non-endometrioid endometrial carcinoma tumors were significantly associated with critical telomere shortening in the adjacent morphologically normal epithelium. Lynch syndrome, which is an autosomal dominantly inherited disorder of cancer susceptibility and is characterized by a MSH2/MSH6 protein complex deficiency, is associated with the development of non-endometrioid carcinomas.
Energy Technology Data Exchange (ETDEWEB)
Yoon, Seok Nam [Kwandong Univ. College of Medicine, Seoul (Korea, Republic of)
2012-09-15
A 35 year old woman with endometrial cancer and cervical extension underwent F18 FDG PET CT and MRI studies after resection of a cervical mass presumed to be cervical myoma. The patient underwent cervical myomectomy and the histopathologic report revealed poorly differentiated invasive carcinoma. Cervical cancer was ruled out because the patient had no history of sexual intercourse and was negative for human papilloma virus infection. The patient underwent radical hysterectomy, bilateral salpingo oophorectomy, pelvic and para aortic lymph node dissection, and multiple biopsies. F18 FDG PET CT showed intense FDG uptake along the cervix wall. T2 weighted MRI also revealed a mass lesion with high SI involving the anterior and posterior lips of the uterine cervix. Another area of focal increased uptake above the endometrial lesion in the left pelvic cavity was observed on PET CT and MRI, possibly due to a functioning ovary. PET CT and MRI were interpreted as showing a dual concordant malignant lesion due to separated FDG uptakes and high SI without any connection between the cervical and endometrial lesions. F18 FDG PET CT showed intense FDG uptake along the endometrium. Given the patient's history and the fact that she was not menstruating at the time of imaging, this intense uptake was interpreted as another pathologic lesion, suggesting dual primary lesions. A suspected heterogeneous mass lesion along the endometrium suggesting concordant endometrial cancer was found on MRI. Endometrial cancer with cervical extension is sometimes difficult to differentiate from primary cervical cancer. The final histopathologic report showed poorly differentiated endometrial adenocarcinoma with cervical extension, although the FDG PET CT and MRI findings were suggestive of concordant cervical and endometrial cancer. Although histopathologic confirmation is necessary for final diagnosis, MRI and FDG PET CT studies may aid in the differential diagnosis. A metastatic cervical mass
International Nuclear Information System (INIS)
Yoon, Seok Nam
2012-01-01
A 35 year old woman with endometrial cancer and cervical extension underwent F18 FDG PET CT and MRI studies after resection of a cervical mass presumed to be cervical myoma. The patient underwent cervical myomectomy and the histopathologic report revealed poorly differentiated invasive carcinoma. Cervical cancer was ruled out because the patient had no history of sexual intercourse and was negative for human papilloma virus infection. The patient underwent radical hysterectomy, bilateral salpingo oophorectomy, pelvic and para aortic lymph node dissection, and multiple biopsies. F18 FDG PET CT showed intense FDG uptake along the cervix wall. T2 weighted MRI also revealed a mass lesion with high SI involving the anterior and posterior lips of the uterine cervix. Another area of focal increased uptake above the endometrial lesion in the left pelvic cavity was observed on PET CT and MRI, possibly due to a functioning ovary. PET CT and MRI were interpreted as showing a dual concordant malignant lesion due to separated FDG uptakes and high SI without any connection between the cervical and endometrial lesions. F18 FDG PET CT showed intense FDG uptake along the endometrium. Given the patient's history and the fact that she was not menstruating at the time of imaging, this intense uptake was interpreted as another pathologic lesion, suggesting dual primary lesions. A suspected heterogeneous mass lesion along the endometrium suggesting concordant endometrial cancer was found on MRI. Endometrial cancer with cervical extension is sometimes difficult to differentiate from primary cervical cancer. The final histopathologic report showed poorly differentiated endometrial adenocarcinoma with cervical extension, although the FDG PET CT and MRI findings were suggestive of concordant cervical and endometrial cancer. Although histopathologic confirmation is necessary for final diagnosis, MRI and FDG PET CT studies may aid in the differential diagnosis. A metastatic cervical mass from
Kato, Kiyoko; Takao, Tomoka; Kuboyama, Ayumi; Tanaka, Yoshihiro; Ohgami, Tatsuhiro; Yamaguchi, Shinichiro; Adachi, Sawako; Yoneda, Tomoko; Ueoka, Yousuke; Kato, Keiji; Hayashi, Shinichi; Asanoma, Kazuo; Wake, Norio
2010-01-01
Cancer stem-like cell subpopulations, referred to as “side-population” (SP) cells, have been identified in several tumors based on their ability to efflux the fluorescent dye Hoechst 33342. Although SP cells have been identified in the normal human endometrium and endometrial cancer, little is known about their characteristics. In this study, we isolated and characterized the SP cells in human endometrial cancer cells and in rat endometrial cells expressing oncogenic human K-Ras protein. These SP cells showed i) reduction in the expression levels of differentiation markers; ii) long-term proliferative capacity of the cell cultures; iii) self-renewal capacity in vitro; iv) enhancement of migration, lamellipodia, and, uropodia formation; and v) enhanced tumorigenicity. In nude mice, SP cells formed large, invasive tumors, which were composed of both tumor cells and stromal-like cells with enriched extracellular matrix. The expression levels of vimentin, α-smooth muscle actin, and collagen III were enhanced in SP tumors compared with the levels in non-SP tumors. In addition, analysis of microdissected samples and fluorescence in situ hybridization of Hec1-SP-tumors showed that the stromal-like cells with enriched extracellular matrix contained human DNA, confirming that the stromal-like cells were derived from the inoculated cells. Moreober, in a Matrigel assay, SP cells differentiated into α-smooth muscle actin-expressing cells. These findings demonstrate that SP cells have cancer stem-like cell features, including the potential to differentiate into the mesenchymal cell lineage. PMID:20008133
Evaluation of endometrial cancer epidemiology in Romania.
Bohîlțea, R E; Furtunescu, F; Dosius, M; Cîrstoiu, M; Radoi, V; Baroș, A; Bohîlțea, L C
2015-01-01
Endometrial cancer represents the most frequent gynecological malignant affection in the developed countries, in which the incidence of cervical cancer has significantly decreased due to the rigorous application of screening methods and prophylaxis. According to its frequency, endometrial cancer is situated on the fourth place in the category of women's genital-mammary malignant diseases, after breast, cervical and ovarian cancer in Romania. The incidence and mortality rates due to endometrial cancer have registered an increasing trend worldwide and also in Romania, a significant decrease of the age of appearance for the entire endometrial pathology sphere being noticed. At the national level, the maximum incidence is situated between 60 and 64 years old, the mortality rate of the women under 65 years old being high in Romania. The study evaluates endometrial cancer, from an epidemiologic point of view, at the national level compared to the international statistic data.
Long-term impact of preeclampsia on maternal endometrial cancer risk
DEFF Research Database (Denmark)
Hallum, Sara; Pinborg, Anja; Kamper-Jørgensen, Mads
2016-01-01
BACKGROUND: Endometrial cancer is mainly dependent on oestrogen exposure. Preeclampsia has shown to reduce oestrogen levels hence preeclampsia may affect later endometrial cancer risk. METHODS: We conducted a case-control study of 523 Danish women with endometrial cancer and 52 299controls during...... 1978-2010. The association between preeclampsia and later endometrial cancer was evaluated overall and according to preeclampsia onset and type of endometrial cancer in conditional logistic regression models. RESULTS: We observed no overall association between preeclampsia and endometrial cancer risk...... (OR=1.11 (95% CI 0.68-1.81)). This was true for all endometrial cancer subtypes. In an analysis of preeclampsia onset, however, we report a markedly increased risk of endometrial cancer following early-onset preeclampsia (OR=2.64 (95% CI 1.29-5.38)). CONCLUSIONS: Although we report no obvious...
Statin use and risk of endometrial cancer
DEFF Research Database (Denmark)
Sperling, Cecilie D.; Verdoodt, Freija; Friis, Soren
2017-01-01
INTRODUCTION: Laboratory and epidemiological evidence have suggested that statin use may protect against the development of certain cancers, including endometrial cancer. In a nationwide registry-based case-control study, we examined the association between statin use and risk of endometrial cancer....... MATERIAL AND METHODS: Cases were female residents of Denmark with a primary diagnosis of endometrial cancer during 2000-2009. For each case, we selected 15 female population controls matched on date of birth (±one month) using risk-set sampling. Ever use of statin was defined as two or more prescriptions...... on separate dates. Conditional logistic regressions were used to estimate age-matched (by design) and multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CI) for endometrial cancer associated with statin use. The multivariable-adjusted models included parity, hormone replacement therapy...
Use of nonsteroidal anti-inflammatory drugs and risk of endometrial cancer
DEFF Research Database (Denmark)
Brøns, Nanna; Baandrup, Louise; Dehlendorff, Christian
2015-01-01
PURPOSE: We examined the association between use of low-dose aspirin and non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) and endometrial cancer risk in a nationwide case-control study. METHODS: Cases were all women in Denmark diagnosed with endometrial cancer during 2000-2009. Age...... with use of low-dose aspirin (OR 0.97, 95 % CI 0.89-1.05) or non-aspirin NSAIDs (OR 0.96, 95 % CI 0.91-1.02) compared with nonuse. The ORs did not vary with increasing duration or intensity of NSAID use or with type of endometrial cancer. Interaction analyses showed reduced endometrial cancer risk...... associated with low-dose aspirin use among nulliparous women (OR 0.82, 95 % CI 0.70-0.95) and with non-aspirin NSAID use among women having used HRT (OR 0.90, 95 % CI 0.82-0.99). CONCLUSIONS: We found no association between use of NSAIDs and endometrial cancer risk overall, although there were some...
DEFF Research Database (Denmark)
Holm, Nina Sofie Lillegaard; Glintborg, Dorte; Andersen, Marianne Skovsager
2012-01-01
Polycystic ovary syndrome may be associated with an increased risk of endometrial hyperplasia and endometrial cancer, but substantial evidence for this remains to be established. We investigated the prevalence of endometrial hyperplasia and endometrial cancer in a well characterized group of women...... with polycystic ovary syndrome and/or clinical/biochemical hyperandrogenism....
Polymorphisms in inflammation pathway genes and endometrial cancer risk
Delahanty, Ryan J.; Xiang, Yong-Bing; Spurdle, Amanda; Beeghly-Fadiel, Alicia; Long, Jirong; Thompson, Deborah; Tomlinson, Ian; Yu, Herbert; Lambrechts, Diether; Dörk, Thilo; Goodman, Marc T.; Zheng, Ying; Salvesen, Helga B.; Bao, Ping-Ping; Amant, Frederic; Beckmann, Matthias W.; Coenegrachts, Lieve; Coosemans, An; Dubrowinskaja, Natalia; Dunning, Alison; Runnebaum, Ingo B.; Easton, Douglas; Ekici, Arif B.; Fasching, Peter A.; Halle, Mari K.; Hein, Alexander; Howarth, Kimberly; Gorman, Maggie; Kaydarova, Dylyara; Krakstad, Camilla; Lose, Felicity; Lu, Lingeng; Lurie, Galina; O’Mara, Tracy; Matsuno, Rayna K.; Pharoah, Paul; Risch, Harvey; Corssen, Madeleine; Trovik, Jone; Turmanov, Nurzhan; Wen, Wanqing; Lu, Wei; Cai, Qiuyin; Zheng, Wei; Shu, Xiao-Ou
2013-01-01
Background Experimental and epidemiological evidence have suggested that chronic inflammation may play a critical role in endometrial carcinogenesis. Methods To investigate this hypothesis, a two-stage study was carried out to evaluate single nucleotide polymorphisms (SNPs) in inflammatory pathway genes in association with endometrial cancer risk. In stage 1, 64 candidate pathway genes were identified and 4,542 directly genotyped or imputed SNPs were analyzed among 832 endometrial cancer cases and 2,049 controls, using data from the Shanghai Endometrial Cancer Genetics Study. Linkage disequilibrium of stage 1 SNPs significantly associated with endometrial cancer (PAsian- and European-ancestry samples. Conclusions These findings lend support to the hypothesis that genetic polymorphisms in genes involved in the inflammatory pathway may contribute to genetic susceptibility to endometrial cancer. Impact Statement This study adds to the growing evidence that inflammation plays an important role in endometrial carcinogenesis. PMID:23221126
Adjuvant radiotherapy for stage I endometrial cancer.
Kong, A; Johnson, N; Cornes, P; Simera, I; Collingwood, M; Williams, C; Kitchener, H
2007-04-18
The role of adjuvant radiotherapy (both pelvic external beam radiotherapy and vaginal intracavity brachytherapy) in stage I endometrial cancer following total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH and BSO) remains unclear. To assess the efficacy of adjuvant radiotherapy following surgery for stage I endometrial cancer. The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CancerLit, Physician Data Query (PDQ) of National Cancer Institute. Handsearching was also carried out where appropriate. Randomised controlled trials (RCTs) which compared adjuvant radiotherapy versus no radiotherapy following surgery for patients with stage I endometrial cancer were included. Quality of the studies was assessed and data collected using a predefined data collection form. The primary endpoint was overall survival. Secondary endpoints were locoregional recurrence, distant recurrence and endometrial cancer death. Data on quality of life (QOL) and morbidity were also collected. A meta-analysis on included trials was performed using the Cochrane Collaboration Review Manager Software 4.2. The meta-analysis was performed on four trials (1770 patients). The addition of pelvic external beam radiotherapy to surgery reduced locoregional recurrence, a relative risk (RR) of 0.28 (95% confidence interval (CI) 0.17 to 0.44, p ASTEC; Lukka) are awaited. External beam radiotherapy carries a risk of toxicity and should be avoided in stage 1 endometrial cancer patients with no high risk factors.
Drugs Approved for Endometrial Cancer
This page lists cancer drugs approved by the Food and Drug Administration (FDA) for endometrial cancer. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.
Role of emmprin in endometrial cancer
Nakamura, Keiichiro; Kodama, Junichi; Hongo, Atsushi; Hiramatsu, Yuji
2012-01-01
Abstract Background Extracellular matrix metalloproteinase inducer (Emmprin/CD147) is a transmembrane glycoprotein that belongs to the immunoglobulin superfamily. Enriched on the surface of many tumor cells, emmprin promotes tumor growth, invasion, metastasis and angiogenesis. We evaluated the clinical importance of emmprin and investigated its role in endometrial cancer. Methods Emmprin expression was examined in uterine normal endometrium, endometrial hyperplasia and cancer specimens by imm...
Endometrial Cancer Treatment (PDQ®)—Health Professional Version
Endometrial cancer is usually diagnosed at an early stage and can be treated with surgery. Learn about the symptoms, diagnosis, prognosis, staging, and treatment for early- and advanced-stage endometrial cancer in this expert-reviewed summary.
Ricceri, Fulvio; Giraudo, Maria Teresa; Fasanelli, Francesca; Milanese, Dario; Sciannameo, Veronica; Fiorini, Laura; Sacerdote, Carlotta
2017-11-13
Endometrial cancer is the fourth most common cancer in European women. The major risk factors for endometrial cancer are related to the exposure of endometrium to estrogens not opposed to progestogens, that can lead to a chronic endometrial inflammation. Diet may play a role in cancer risk by modulating chronic inflammation. In the framework of a case-control study, we recruited 297 women with newly diagnosed endometrial cancer and 307 controls from Northern Italy. Using logistic regression, we investigated the role of fruit and vegetable intake, adherence to the Mediterranean diet (MD), and the dietary inflammatory index (DII) in endometrial cancer risk. Women in the highest quintile of vegetable intake had a statistically significantly lower endometrial cancer risk (adjusted OR 5th quintile vs 1st quintile: 0.34, 95% CI 0.17-0.68). Women with high adherence to the MD had a risk of endometrial cancer that was about half that of women with low adherence to the MD (adjusted OR: 0.51, 95% CI 0.39-0.86). A protective effect was detected for all the lower quintiles of DII, with the highest protective effect seen for the lowest quintile (adjusted OR 5th quintile vs 1st quintile: 3.28, 95% CI 1.30-8.26). These results suggest that high vegetable intake, adherence to the MD, and a low DII are related to a lower endometrial cancer risk, with several putative connected biological mechanisms that strengthen the biological plausibility of this association.
Progesterone inhibits epithelial-to-mesenchymal transition in endometrial cancer.
Directory of Open Access Journals (Sweden)
Paul H van der Horst
Full Text Available BACKGROUND: Every year approximately 74,000 women die of endometrial cancer, mainly due to recurrent or metastatic disease. The presence of tumor infiltrating lymphocytes (TILs as well as progesterone receptor (PR positivity has been correlated with improved prognosis. This study describes two mechanisms by which progesterone inhibits metastatic spread of endometrial cancer: by stimulating T-cell infiltration and by inhibiting epithelial-to-mesenchymal cell transition (EMT. METHODOLOGY AND PRINCIPAL FINDINGS: Paraffin sections from patients with (n = 9 or without (n = 9 progressive endometrial cancer (recurrent or metastatic disease were assessed for the presence of CD4+ (helper, CD8+ (cytotoxic and Foxp3+ (regulatory T-lymphocytes and PR expression. Progressive disease was observed to be associated with significant loss of TILs and loss of PR expression. Frozen tumor samples, used for genome-wide expression analysis, showed significant regulation of pathways involved in immunesurveillance, EMT and metastasis. For a number of genes, such as CXCL14, DKK1, DKK4, PEG10 and WIF1, quantitive RT-PCR was performed to verify up- or downregulation in progressive disease. To corroborate the role of progesterone in regulating invasion, Ishikawa (IK endometrial cancer cell lines stably transfected with PRA (IKPRA, PRB (IKPRB and PRA+PRB (IKPRAB were cultured in presence/absence of progesterone (MPA and used for genome-wide expression analysis, Boyden- and wound healing migration assays, and IHC for known EMT markers. IKPRB and IKPRAB cell lines showed MPA induced inhibition of migration and loss of the mesenchymal marker vimentin at the invasive front of the wound healing assay. Furthermore, pathway analysis of significantly MPA regulated genes showed significant down regulation of important pathways involved in EMT, immunesuppression and metastasis: such as IL6-, TGF-β and Wnt/β-catenin signaling. CONCLUSION: Intact progesterone signaling in non
Recent Advances in Endometrial Cancer [version 1; referees: 2 approved
Directory of Open Access Journals (Sweden)
Arthur-Quan Tran
2017-01-01
Full Text Available Endometrial cancer is the most common gynecologic malignancy in the United States, with yearly rates continuing to increase. Most women present with early stage disease; however, advanced disease carries a grave prognosis. As a result, novel therapies are currently under investigation for the treatment of endometrial cancer. These advances include a better understanding of the genetic basis surrounding the development of endometrial cancer, novel surgical therapies, and new molecular targets for the treatment of this disease. This review explores the literature regarding these advancements in endometrial cancer.
Directory of Open Access Journals (Sweden)
Takashi Takeda
2016-10-01
Full Text Available Germline mutation of DNA mismatch repair (MMR genes is a cause of Lynch syndrome. Methylation of MutL homolog 1 (MLH1 and MutS homolog 2 (MSH2 has been detected in peripheral blood cells of patients with colorectal cancer. This methylation is referred to as epimutation. Methylation of these genes has not been studied in an unselected series of endometrial cancer cases. Therefore, we examined methylation of MLH1, MSH2, and MSH6 promoter regions of peripheral blood cells in 206 patients with endometrial cancer using a methylation-specific polymerase chain reaction (MSP. Germline mutation of MMR genes, microsatellite instability (MSI, and immunohistochemistry (IHC were also analyzed in each case with epimutation. MLH1 epimutation was detected in a single patient out of a total of 206 (0.49%—1 out of 58 (1.72% with an onset age of less than 50 years. The patient with MLH1 epimutation showed high level MSI (MSI-H, loss of MLH1 expression and had developed endometrial cancer at 46 years old, complicated with colorectal cancer. No case had epimutation of MSH2 or MSH6. The MLH1 epimutation detected in a patient with endometrial cancer may be a cause of endometrial carcinogenesis. This result indicates that it is important to check epimutation in patients with endometrial cancer without a germline mutation of MMR genes.
Prevalence of Human Papillomavirus in endometrial cancer
DEFF Research Database (Denmark)
Olesen, Tina Bech; Svahn, Malene Frøsig; Faber, Mette Tuxen
2014-01-01
HPV is a common sexually transmitted infection and is considered to be a necessary cause of cervical cancer. The anatomical proximity to the cervix has led researchers to investigate whether Human Papillomavirus (HPV) has a role in the etiology of endometrial cancer.......HPV is a common sexually transmitted infection and is considered to be a necessary cause of cervical cancer. The anatomical proximity to the cervix has led researchers to investigate whether Human Papillomavirus (HPV) has a role in the etiology of endometrial cancer....
Yang, H P; Cook, L S; Weiderpass, E; Adami, H-O; Anderson, K E; Cai, H; Cerhan, J R; Clendenen, T V; Felix, A S; Friedenreich, C M; Garcia-Closas, M; Goodman, M T; Liang, X; Lissowska, J; Lu, L; Magliocco, A M; McCann, S E; Moysich, K B; Olson, S H; Petruzella, S; Pike, M C; Polidoro, S; Ricceri, F; Risch, H A; Sacerdote, C; Setiawan, V W; Shu, X O; Spurdle, A B; Trabert, B; Webb, P M; Wentzensen, N; Xiang, Y-B; Xu, Y; Yu, H; Zeleniuch-Jacquotte, A; Brinton, L A
2015-01-01
Background: Nulliparity is an endometrial cancer risk factor, but whether or not this association is due to infertility is unclear. Although there are many underlying infertility causes, few studies have assessed risk relations by specific causes. Methods: We conducted a pooled analysis of 8153 cases and 11 713 controls from 2 cohort and 12 case-control studies. All studies provided self-reported infertility and its causes, except for one study that relied on data from national registries. Logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI). Results: Nulliparous women had an elevated endometrial cancer risk compared with parous women, even after adjusting for infertility (OR=1.76; 95% CI: 1.59–1.94). Women who reported infertility had an increased risk compared with those without infertility concerns, even after adjusting for nulliparity (OR=1.22; 95% CI: 1.13–1.33). Among women who reported infertility, none of the individual infertility causes were substantially related to endometrial cancer. Conclusions: Based on mainly self-reported infertility data that used study-specific definitions of infertility, nulliparity and infertility appeared to independently contribute to endometrial cancer risk. Understanding residual endometrial cancer risk related to infertility, its causes and its treatments may benefit from large studies involving detailed data on various infertility parameters. PMID:25688738
Directory of Open Access Journals (Sweden)
Gang Feng
2014-01-01
Full Text Available Purpose. The purpose of this study was to analyze the expression of zinc-finger E-box-binding homeobox 1 (ZEB1 in endometrial biopsy and its correlation with preoperative characteristics, including lymph node metastases in patient with endometrial cancer. Methods. Using quantitative RT-PCR, ZEB1 expressions in endometrial biopsy from 452 patients were measured. The relationship between ZEB1 expression and preoperative characteristics was analyzed. Results. ZEB1 expressions were significantly associated with subtype, grade, myometrial invasion, and lymph node metastases. Lymph node metastases could be identified with a sensitivity of 57.8% at specificity of 74.1% by ZEB1 expression in endometrial biopsy. Based on combination of preoperative characteristics and ZEB1 expression, lymph node metastases could be identified with a sensitivity of 62.1% at specificity of 96.2% prior to hysterectomy. Conclusion. ZEB1 expression in endometrial biopsy could help physicians to better predict the lymph node metastasis in patients with endometrial cancer prior to hysterectomy.
EARLY RECURRENCE OF WELL-DIFFERENTIATED ENDOMETRIAL CANCER (A CASE REPORT
Directory of Open Access Journals (Sweden)
N. E. Levchrnko
2017-01-01
Full Text Available Endometrial cancer is the 6-th most common malignancy in women worldwide, accounting for about 4.8 % of all female cancers. The treatment of recurrent endometrial cancer remains a major challenge. Some endometrial cancer recurrences, for example vaginal stump recurrence, are reported to be effectively treated with surgical resection and radiation therapy. Early recurrence of early-stage well-differentiated endometrial cancer is uncommon. Case report. Herein we report a rare case of recurrent well-differentiated endometrial cancer in a 65-year-old woman. The patient had recurrence 10 months after laparoscopic hysterectomy with bilateral salpingo-oophorectomy. Recurrent endometrial tumor with extension into the rectosigmoid colon, urinary bladder and the right ureter manifested itself clinically with severe pain requiring the use of opioids. The recurrent tumor was removed. Resection of the bladder, left ureter and upper ampular rectum was followed by anastomosis. The patient received multiple cycles of chemotherapy. Conclusion. Compliance with the principles of ablastics during the laparoscopic or laparotomic surgery helps to avoid recurrence in patients with prognostically favorable cancer. In case of recurrence, combined operations are the only possible chance of improving survival of patients with locally advanced or recurrent tumors, which are insensitive to chemoradiotherapy.
Premenopausal abnormal uterine bleeding and risk of endometrial cancer.
Pennant, M E; Mehta, R; Moody, P; Hackett, G; Prentice, A; Sharp, S J; Lakshman, R
2017-02-01
Endometrial biopsies are undertaken in premenopausal women with abnormal uterine bleeding but the risk of endometrial cancer or atypical hyperplasia is unclear. To conduct a systematic literature review to establish the risk of endometrial cancer and atypical hyperplasia in premenopausal women with abnormal uterine bleeding. Search of PubMed, Embase and the Cochrane Library from database inception to August 2015. Studies reporting rates of endometrial cancer and/or atypical hyperplasia in women with premenopausal abnormal uterine bleeding. Data were independently extracted by two reviewers and cross-checked. For each outcome, the risk and a 95% CI were estimated using logistic regression with robust standard errors to account for clustering by study. Sixty-five articles contributed to the analysis. Risk of endometrial cancer was 0.33% (95% CI 0.23-0.48%, n = 29 059; 97 cases) and risk of endometrial cancer or atypical hyperplasia was 1.31% (95% CI 0.96-1.80, n = 15 772; 207 cases). Risk of endometrial cancer was lower in women with heavy menstrual bleeding (HMB) (0.11%, 95% CI 0.04-0.32%, n = 8352; 9 cases) compared with inter-menstrual bleeding (IMB) (0.52%, 95% CI 0.23-1.16%, n = 3109; 14 cases). Of five studies reporting the rate of atypical hyperplasia in women with HMB, none identified any cases. The risk of endometrial cancer or atypical hyperplasia in premenopausal women with abnormal uterine bleeding is low. Premenopausal women with abnormal uterine bleeding should first undergo conventional medical management. Where this fails, the presence of IMB and older age may be indicators for further investigation. Further research into the risks associated with age and the cumulative risk of co-morbidities is needed. Contrary to practice, premenopausal women with heavy periods or inter-menstrual bleeding rarely require biopsy. © 2016 The Authors BJOG An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd on behalf of Royal
Abnormal expression of blood group-related antigens in uterine endometrial cancers.
Tsukazaki, K; Sakayori, M; Arai, H; Yamaoka, K; Kurihara, S; Nozawa, S
1991-08-01
The expression of A, B, and H group antigens, Lewis group antigens (Lewis(a), Lewis(b), Lewis(x), and Lewis(y)), and Lc4 and nLc4 antigens, the precursor antigens of both groups, was examined immunohistochemically with monoclonal antibodies in 9 normal endometria, 6 endometrial hyperplasias, and 31 endometrial cancers. 1) A, B and/or H antigens were detected in endometrial cancers at an incidence of 51.6%, while no distinct localization of these antigens was observed in normal endometria. H antigen, the precursor of A and B antigens, was particularly frequently detected in endometrial cancers. 2) An increased rate of expression of Lewis group antigens, particularly Lewis(b) antigen, was observed in endometrial cancers compared with its expression in normal endometria. 3) Lc4 and nLc4 antigens were detected in endometrial cancers at rates of 41.9% and 38.7%, respectively, these expressions being increased compared with those in normal endometria. 4) These results suggest that a highly abnormal expression of blood group-related antigens in endometrial cancers occurs not only at the level of A, B, and H antigens and Lewis group antigens, but also at the level of their precursor Lc4 and nLc4 antigens. 5) Lewis(a), Lewis(b), and Lc4 antigens, built on the type-1 chain, are more specific to endometrial cancers than their respective positional isomers, Lewis(x), Lewis(y), and nLc4 antigens, built on the type-2 chain.
Sperm protein 17 is highly expressed in endometrial and cervical cancers
International Nuclear Information System (INIS)
Li, Fang-qiu; Liu, Qun; Han, Yan-ling; Wu, Bo; Yin, Hong-lin
2010-01-01
Sperm protein 17 (Sp17) is a highly conserved mammalian protein in the testis and spermatozoa and has been characterized as a tumor-associated antigen in a variety of human malignancies. Many studies have examined the role of Sp17 in tumorigenesis and the migration of malignant cells. It has been proposed as a useful target for tumor-vaccine strategies and a novel marker to define tumor subsets and predict drug response. This study aimed to investigate the expression of Sp17 in endometrial and cervical cancer specimens, its possible correlation with the pathological characteristics, and its value in the diagnosis and immunotherapy of the related cancers. The monoclonal antibodies against human Sp17 were produced as reagents for the analysis and immunohistochemistry was used to study two major kinds of paraffin-embedded gynecological cancer specimens, including 50 cases of endometrial cancer (44 adenous and 6 adenosquamous) and 31 cases of cervical cancer (15 adenous and 16 squamous). Normal peripheral endometrial and cervical tissues were used as controls. Sp17 was found in 66% (33/50) of the patients with endometrial cancer and 61% (19/31) of those with cervical cancer. Its expression was found in a heterogeneous pattern in the cancer tissues. The expression was not correlated with the histological subtype and grade of malignancy, but the staining patterns were different in endometrial and cervical cancers. The hyperplastic glands were positive for Sp17 in the normal peripheral endometrial and cervical tissues in 10% (8/81) of the patients. Sp17 is highly expressed in human endometrial and cervical cancers in a heterogeneous pattern. Although the expression frequency of Sp17 is not correlated with the histological subtype, the staining pattern may help to define endometrial and cervical cancers. Sp17 targeted immunotherapy of tumors needs more accurate validation
DEFF Research Database (Denmark)
Ketabi, Zohreh; Mosgaard, Berit J; Gerdes, Anne-Marie
2012-01-01
Women with hereditary nonpolyposis colorectal cancer (HNPCC) have a 40-60% lifetime risk for endometrial cancer. Guidelines in Denmark recommend gynecologic screening for female members of families with HNPCC. We estimated the knowledge of endometrial cancer risk and identified possible predictors...
Prognostic significance of miR-205 in endometrial cancer.
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Mihriban Karaayvaz
Full Text Available microRNAs have emerged as key regulators of gene expression, and their altered expression has been associated with tumorigenesis and tumor progression. Thus, microRNAs have potential as both cancer biomarkers and/or potential novel therapeutic targets. Although accumulating evidence suggests the role of aberrant microRNA expression in endometrial carcinogenesis, there are still limited data available about the prognostic significance of microRNAs in endometrial cancer. The goal of this study is to investigate the prognostic value of selected key microRNAs in endometrial cancer by the analysis of archival formalin-fixed paraffin-embedded tissues.Total RNAs were extracted from 48 paired normal and endometrial tumor specimens using Trizol based approach. The expression of miR-26a, let-7g, miR-21, miR-181b, miR-200c, miR-192, miR-215, miR-200c, and miR-205 were quantified by real time qRT-PCR expression analysis. Targets of the differentially expressed miRNAs were quantified using immunohistochemistry. Statistical analysis was performed by GraphPad Prism 5.0.The expression levels of miR-200c (P<0.0001 and miR-205 (P<0.0001 were significantly increased in endometrial tumors compared to normal tissues. Kaplan-Meier survival analysis revealed that high levels of miR-205 expression were associated with poor patient overall survival (hazard ratio, 0.377; Logrank test, P = 0.028. Furthermore, decreased expression of a miR-205 target PTEN was detected in endometrial cancer tissues compared to normal tissues.miR-205 holds a unique potential as a prognostic biomarker in endometrial cancer.
Endometrial and cervical cancer: incidence and mortality among women in the Lodz region
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Beata Leśniczak
2015-09-01
Full Text Available Introduction: By the early 21st century the most common cancer of female genitals in Poland was cervical cancer. Now endometrial cancer ranks first. The aim of this study was to analyse the incidence and mortality of endometrial and cervical cancer among women in the Lodz region. Material and methods: Data on the incidence and mortality of endometrial and cervical cancer among inhabitants of the Lodz region were obtained from the National Cancer Registry and Bulletin of Cancer Cases in the Lodz region. The analysis covered ten consecutive years beginning in 2001. Results : The number of new cases reported in 2010 exceeded that observed in 2001 by 181. The standardized incidence rate of endometrial cancer increased by 6.3, while the standardized incidence rate of cervical cancer decreased by 1.4. Conclusions : In the years 2001-2010, the incidence of endometrial cancer increased by 88.3% and that of cervical cancer decreased by 6.5% among inhabitants of the Lodz region. In the years 2001-2010, mortality of endometrial cancer increased by 24.5% and that of cervical cancer decreased by 12.6%. In 2010, the highest crude incidence rates in the Lodz region of both endometrial and cervical cancer at 39.1 were recorded in the district town of Piotrków.
Short Course Vaginal Cuff Brachytherapy in Treating Patients With Stage I-II Endometrial Cancer
2018-04-17
Endometrial Clear Cell Adenocarcinoma; Endometrial Endometrioid Adenocarcinoma; Endometrial Serous Adenocarcinoma; Stage I Uterine Corpus Cancer; Stage IA Uterine Corpus Cancer; Stage IB Uterine Corpus Cancer; Stage II Uterine Corpus Cancer; Uterine Corpus Carcinosarcoma; Uterine Corpus Sarcoma
Niskakoski, Anni; Pasanen, Annukka; Lassus, Heini; Renkonen-Sinisalo, Laura; Kaur, Sippy; Mecklin, Jukka-Pekka; Bützow, Ralf; Peltomäki, Päivi
2018-03-27
Molecular alterations preceding endometrial and ovarian cancer and the sequence of events are unknown. Consecutive specimens from lifelong surveillance for Lynch syndrome provides a natural setting to address such questions. To molecularly define the multistep gynecological tumorigenesis, DNA mismatch repair gene mutation carriers with endometrial or ovarian carcinoma or endometrial hyperplasia were identified from a nation-wide registry and endometrial biopsy specimens taken from these individuals during 20 years of screening were collected. A total of 213 endometrial and ovarian specimens from Lynch syndrome individuals and 197 histology-matched (non-serous) samples from sporadic cases were available for this investigation. The specimens were profiled for markers linked to endometrial and ovarian tumorigenesis, including ARID1A protein expression, mismatch repair status, and tumor suppressor gene promoter methylation. In Lynch syndrome-associated endometrial and ovarian carcinomas, ARID1A protein was lost in 61-100% and mismatch repair was deficient in 97-100%, compared to 0-17% and 14-44% in sporadic cases (P = 0.000). ARID1A loss appeared in complex hyperplasia and deficient mismatch repair and tumor suppressor gene promoter methylation in histologically normal endometrium. Despite quantitative differences between Lynch syndrome and sporadic cases, ARID1A expression, mismatch repair, and tumor suppressor gene promoter methylation divided endometrial samples from both patient groups into three categories of increasing abnormality, comprising normal endometrium and simple hyperplasia (I), complex hyperplasia with or without atypia (II), and endometrial cancer (III). Complex hyperplasias without vs. with atypia were molecularly indistinguishable. In conclusion, surveillance specimens from Lynch syndrome identify mismatch repair deficiency, tumor suppressor gene promoter methylation, and ARID1A loss as early changes in tumor development. Our findings are
Endometrial thickness as a test for endometrial cancer in women with postmenopausal vaginal bleeding
DEFF Research Database (Denmark)
Tabor, Ann; Watt, Hilary C; Wald, Nicholas J
2002-01-01
OBJECTIVE: To assess the value of endometrial thickness measurement as a test for endometrial cancer in postmenopausal women with vaginal bleeding (symptomatic women). DATA SOURCES: We conducted a literature search using the MEDLINE database from 1991 to 1997, and the key words "vaginal...... ultrasonography" and "endometrial thickness measurement." The review was limited to original research reports written in English, concerning symptomatic women having vaginal ultrasonography before a diagnostic test and not receiving tamoxifen. STUDY SELECTION: A total of 48 studies were identified...
The role of miRNAs in endometrial cancer.
Vasilatou, Diamantina; Sioulas, Vasileios D; Pappa, Vasiliki; Papageorgiou, Sotirios G; Vlahos, Nikolaos F
2015-01-01
miRNAs are small noncoding RNAs that regulate gene expression at the post-transcriptional level. Since their discovery, miRNAs have been associated with every cell function including malignant transformation and metastasis. Endometrial cancer is the most common gynecologic malignancy. However, improvement should be made in interobserver agreement on histological typing and individualized therapeutic approaches. This article summarizes the role of miRNAs in endometrial cancer pathogenesis and treatment.
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Liang Ma
2013-08-01
Full Text Available Alternative strategies beyond current chemotherapy and radiation therapy regimens are needed in the treatment of advanced stage and recurrent endometrial cancers. There is considerable promise for biologic agents targeting the extracellular signal-regulated kinase (ERK pathway for treatment of these cancers. Many downstream substrates of the ERK signaling pathway, such as glycogen synthase kinase 3β (GSK3β, and their roles in endometrial carcinogenesis have not yet been investigated. In this study, we tested the importance of GSK3β inhibition in endometrial cancer cell lines and in vivo models. Inhibition of GSK3β by either lithium chloride (LiCl or specific GSK3β inhibitor VIII showed cytostatic and cytotoxic effects on multiple endometrial cancer cell lines, with little effect on the immortalized normal endometrial cell line. Flow cytometry and immunofluorescence revealed a G2/M cell cycle arrest in both type I (AN3CA, KLE, and RL952 and type II (ARK1 endometrial cancer cell lines. In addition, LiCl pre-treatment sensitized AN3CA cells to the chemotherapy agent paclitaxel. Administration of LiCl to AN3CA tumor-bearing mice resulted in partial or complete regression of some tumors. Thus, GSK3β activity is associated with endometrial cancer tumorigenesis and its pharmacologic inhibition reduces cell proliferation and tumor growth.
Sun, Pengming; Xue, Lifang; Song, Yiyi; Mao, Xiaodan; Chen, Lili; Dong, Binhua; Braicu, Elena Loana; Sehouli, Jalid
2018-02-27
The effects of specific and non-specific regulation of matriptase on endometrial cancer cells in vitro were investigated. Messenger ribonucleic acid (mRNA) and protein expression of matriptase and hepatocyte growth factor activator inhibitor-1 (HAI-1) in RL-952, HEC-1A, and HEC-1B endometrial cancer cells were detected by real-time quantitative PCR (RT-qPCR) and western blot. The cells were infected with lentivirus-mediated small-interfering RNA (siRNA) targeted on matriptase (MA-siRNA) or treated with different cisplatin (DDP) concentrations. After treatment, invasion, migration, and cellular apoptosis were analyzed. Matriptase mRNA and protein expression significantly decreased to 80% after infection with MA-siRNA ( P scratch and trans-well chamber assays showed significant inhibition of invasiveness and metastasis. Upon incubation with cisplatin at concentrations higher than the therapeutic dose for 24 h, the expressions of matriptase and HAI-1 significantly decreased ( P endometrial cancer cells were significantly decreased ( P endometrial cancer cells showed promising therapeutic features.
Non-steroidal anti-inflammatory drug use and risk of endometrial cancer
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Verdoodt, Freija; Friis, Søren; Dehlendorff, Christian
2016-01-01
OBJECTIVE: Non-steroidal anti-inflammatory drug (NSAID) use has been linked to a reduction in the risk of several cancer types. For endometrial cancer, however, results have been inconsistent. To summarize the available evidence on the risk of endometrial cancer associated with use of aspirin...... a random effects model. RESULTS: Six case-control and seven cohort studies were found eligible for our meta-analysis. We observed risk reductions in endometrial cancer associated with regular use of aspirin (case-control: 11%, cohort: 8%) and NA-NSAIDs (case-control: 9%, cohort: 6%), compared to non...
Adjuvant vaginal brachytherapy as a part of management in early endometrial cancer.
Kellas-Ślęczka, Sylwia; Wojcieszek, Piotr; Białas, Brygida
2012-12-01
Endometrial cancer is the most frequent cancer of female genital tract. Metro- and menorrhagia or postmenopausal bleeding results in its early presentation. It allows radical treatment. However, controversies remain on surgery coverage or adjuvant therapies in early endometrial women cancer. Optimal management should minimize intervention instead of aggressive approach, as showed by recent studies. There is a role for brachytherapy as an adjuvant irradiation. Crucial publications including PORTEC-1, GOG 99, MRC ASTEC, ASTEC/EN.5, PORTEC-2 or Italian lymphadenectomy trial are discussed. Moreover, there is attention paid on adjuvant vaginal brachytherapy analyses for the past fifteen years.
Preclinical Studies of Chemotherapy Using Histone Deacetylase Inhibitors in Endometrial Cancer
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Noriyuki Takai
2010-01-01
Full Text Available Because epigenetic alterations are believed to be involved in the repression of tumor suppressor genes and promotion of tumorigenesis in endometrial cancers, novel compounds endowed with a histone deacetylase (HDAC inhibitory activity are an attractive therapeutic approach. In this review, we discuss the biologic and therapeutic effects of HDAC inhibitors (HDACIs in treating endometrial cancer. HDACIs were able to mediate inhibition of cell growth, cell cycle arrest, apoptosis, and the expression of genes related to the malignant phenotype in a variety of endometrial cancer cell lines. Furthermore, HDACIs were able to induce the accumulation of acetylated histones in the chromatin of the p21WAF1 gene in human endometrial carcinoma cells. In xenograft models, some HDACIs have demonstrated antitumor activity with only few side effects. In this review, we discuss the biologic and therapeutic effects of HDACIs in treating endometrial cancer, with a special focus on preclinical studies.
Wu, Xihai; Miao, Jilan; Jiang, Jingyan; Liu, Fangmei
2017-10-01
Endometrial cancer is a prevalent cancer, and its metastasis causes low survival rate. This study aims to utilize DNA methylation data to investigate the mechanism of the development and metastasis of endometrial cancer. Methylation profiling data were down-loaded from Gene Expression Omnibus, including 8 hyperplasias, 33 primary and 53 metastatic endometrial cancers. COHCAP package and annotation files were utilized to identify differentially methylated genes (DMGs) and CpG islands between the three different endometrial diseases. STRING database and Cytoscape were used to analyze and visualize protein-protein interactions (PPIs) between DMGs. CytoNCA plugin was utilized to identify key nodes in PPI network. A total of 610, 1076, and 501 DMGs were identified between primary endometrial cancer and hyperplasia, metastatic endometrial cancer and hyperplasia, as well as metastatic and primary endometrial cancers, respectively. For the three DMG sets, 53 common hypermethylated DMGs (e.g. PAX6 and INSR) and 6 common hypomethylated DMGs (e.g. PRDM8, KLHL14, and DUSP6) were found. For primary-hyperplasia DMG set and metastasis-hyperplasia DMG set, 527 common DMGs were found. For these common DMGs, a PPI network involving 692 PPIs was constructed. For DMGs between metastatic and primary endometrial cancers, a PPI network involving 673 PPIs was established, with PAX6 and INSR in the top 20 DMGs in both networks. PRDM8, KLHL14, and DUSP6 had hypomethylated CpG islands. DMGs comparison, PPI network analysis, and analysis of differentially methylated CpG islands indicated that PAX6, INSR, PRDM8, KLHL14, and DUSP6 might participate in the development and metastasis of endometrial cancer. Copyright © 2017. Published by Elsevier B.V.
The importance of family history in young patients with endometrial cancer
Berends, MJW; Kleibeuker, JH; de Vries, EGE; Mourits, MJE; Hollema, H; Pras, E; van der Zee, AGJ
Endometrial cancer occurs primarily in postmenopausal women older than 60 years of age. Especially in young patients with endometrial cancer, a positive family history with respect to cancer and/or development of synchronous or metachronous tumors can be indicative of hereditary factors. One generic
Progestin and estrogen potency of combination oral contraceptives and endometrial cancer risk.
Maxwell, G L; Schildkraut, J M; Calingaert, B; Risinger, J I; Dainty, L; Marchbanks, P A; Berchuck, A; Barrett, J C; Rodriguez, G C
2006-11-01
Using data from a case-control study of endometrial cancer, we investigated the relationship between the progestin and estrogen potency in combination oral contraceptives (OCs) and the risk of developing endometrial cancer. Subjects included 434 endometrial cancer cases and 2,557 controls identified from the Cancer and Steroid Hormone (CASH) study. OCs were classified into four categories according to the individual potencies of each hormonal constituent (high versus low estrogen or progestin potency). Logistic regression was used to evaluate associations between endometrial cancer risk and combination OC formulations. With non-users as the referent group, use of OCs with either high potency progestin [odds ratio for endometrial cancer (OR)=0.21, 95% confidence interval (CI)=0.10 to 0.43] or with low potency progestin (OR=0.39, 95% CI=0.25 to 0.60) were both associated with a decreased risk of endometrial cancer. Overall high progestin potency OCs did not confer significantly more protection than low progestin potency OCs (OR=0.52, 95% CI=0.24 to 1.14). However, among women with a body mass index of 22.1 kg/m2 or higher, those who used high progestin potency oral contraceptives had a lower risk of endometrial cancer than those who used low progestin potency oral contraceptives (OR=0.31, 95% CI=0.11 to 0.92) while those with a BMI below 22.1 kg/m2 did not (OR=1.36, 95% CI=0.39 to 4.70). The potency of the progestin in most OCs appears adequate to provide a protective effect against endometrial cancer. Higher progestin-potency OCs may be more protective than lower progestin potency OCs among women with a larger body habitus.
Bourdel, Nicolas; Chauvet, Pauline; Tognazza, Enrica; Pereira, Bruno; Botchorishvili, Revaz; Canis, Michel
2016-01-01
Our objective was to identify the most accurate method of endometrial sampling for the diagnosis of complex atypical hyperplasia (CAH), and the related risk of underestimation of endometrial cancer. We conducted a systematic literature search in PubMed and EMBASE (January 1999-September 2013) to identify all registered articles on this subject. Studies were selected with a 2-step method. First, titles and abstracts were analyzed by 2 reviewers, and 69 relevant articles were selected for full reading. Then, the full articles were evaluated to determine whether full inclusion criteria were met. We selected 27 studies, taking into consideration the comparison between histology of endometrial hyperplasia obtained by diagnostic tests of interest (uterine curettage, hysteroscopically guided biopsy, or hysteroscopic endometrial resection) and subsequent results of hysterectomy. Analysis of the studies reviewed focused on 1106 patients with a preoperative diagnosis of atypical endometrial hyperplasia. The mean risk of finding endometrial cancer at hysterectomy after atypical endometrial hyperplasia diagnosed by uterine curettage was 32.7% (95% confidence interval [CI], 26.2-39.9), with a risk of 45.3% (95% CI, 32.8-58.5) after hysteroscopically guided biopsy and 5.8% (95% CI, 0.8-31.7) after hysteroscopic resection. In total, the risk of underestimation of endometrial cancer reaches a very high rate in patients with CAH using the classic method of evaluation (i.e., uterine curettage or hysteroscopically guided biopsy). This rate of underdiagnosed endometrial cancer leads to the risk of inappropriate surgical procedures (31.7% of tubal conservation in the data available and no abdominal exploration in 24.6% of the cases). Hysteroscopic resection seems to reduce the risk of underdiagnosed endometrial cancer. Copyright © 2016 AAGL. Published by Elsevier Inc. All rights reserved.
Self-reported stress and risk of endometrial cancer: a prospective cohort study
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Nielsen, Naja Rod; Strandberg-Larsen, Katrine; Grønbaek, Morten
2007-01-01
OBJECTIVES: To assess a possible relationship between perceived stress and first-time incidence of primary endometrial cancer. Psychological stress may affect the synthesis and metabolism of estrogens and thereby be related to risk of endometrial cancer. METHODS: The 6760 women participating...... in the Copenhagen City Heart Study were asked about their stress level at baseline from 1981 to 1983. These women were prospectively followed up in the Danish nationwide cancer registry until 2000 and ...-up, 72 women were diagnosed with endometrial cancer. For each increase in stress level on a 7-point stress scale, there was a lower risk of primary endometrial cancer (hazard ratio (HR) = 0.88; 95% confidence interval (CI), 0.76-1.01). This inverse association was particularly strong in women who...
Childhood BMI growth trajectories and endometrial cancer risk
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Aarestrup, Julie; Gamborg, Michael; Tilling, Kate
2017-01-01
Previously, we found that excess weight already in childhood has positive associations with endometrial cancer, however, associations with changes in body mass index (BMI) during childhood are not well understood. Therefore, we examined whether growth in childhood BMI is associated with endometrial...... cancer and its sub-types. A cohort of 155,505 girls from the Copenhagen School Health Records Register with measured weights and heights at the ages of 6 to 14 years and born 1930-89 formed the analytical population. BMI was transformed to age-specific z-scores. Using linear spline multilevel models......, each girl's BMI growth trajectory was estimated as the deviance from the average trajectory for three different growth periods (6.25-7.99, 8.0-10.99, 11.0-14.0 years). Via a link to health registers, 1020 endometrial cancer cases were identified, and Cox regressions were performed. A greater gain...
MR imaging of endometrial cancer that occurs after radiation therapy for cervix cancer
International Nuclear Information System (INIS)
Kim, Youn Jeong; Jeong, Yong Yeon; Lim, Nam Yeol; Ko, Seok Wan; Kim, Bo Hyun
2007-01-01
We wanted to describe the MR imaging findings of endometrial cancer in patients with a history of prior radiation therapy for cervical cancer (ECRT) and we compare them to the MR imaging findings of patients with spontaneously occurring endometrial cancer (SEC). Twenty-two patients with endometrial cancer that was diagnosed by operation or endometrial biopsy were included in the study. The patients were divided into two groups according to the presence of past RT for cervical cancer: ECRT (n = 4) and SEC (n = 18). The MR images were retrospectively analyzed by consensus of two experienced radiologists. The MR imaging findings were analyzed by the size, shape and signal intensity of the mass, distension of the uterine cavity, the presence of cervical stenosis and the nature of the fluid collection. For the mass shape, all the ECRT lesions were polypoid masses. However, the SEC patients had 5 polypoid masses and 13 wall thickenings. The maximal diameter, signal intensity and enhancement pattern of the masses were not different between the ECRT and SEC patients. The width of the endometrial cavity varied between 3.9 cm in the ECRT patients and 0.4 cm in the SEC patients (ρ = 0.002). All the ECRT patients had cervical stenosis. However, none of the SEC patients had cervical stenosis. MR imaging of ECRT patients demonstrated prominent distension of their uterine cavity and cervical stenosis, which may be the result of radiation fibrosis in the uterus
Role of DNA methylation and epigenetic silencing of HAND2 in endometrial cancer development.
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Allison Jones
2013-11-01
Full Text Available Endometrial cancer incidence is continuing to rise in the wake of the current ageing and obesity epidemics. Much of the risk for endometrial cancer development is influenced by the environment and lifestyle. Accumulating evidence suggests that the epigenome serves as the interface between the genome and the environment and that hypermethylation of stem cell polycomb group target genes is an epigenetic hallmark of cancer. The objective of this study was to determine the functional role of epigenetic factors in endometrial cancer development.Epigenome-wide methylation analysis of >27,000 CpG sites in endometrial cancer tissue samples (n = 64 and control samples (n = 23 revealed that HAND2 (a gene encoding a transcription factor expressed in the endometrial stroma is one of the most commonly hypermethylated and silenced genes in endometrial cancer. A novel integrative epigenome-transcriptome-interactome analysis further revealed that HAND2 is the hub of the most highly ranked differential methylation hotspot in endometrial cancer. These findings were validated using candidate gene methylation analysis in multiple clinical sample sets of tissue samples from a total of 272 additional women. Increased HAND2 methylation was a feature of premalignant endometrial lesions and was seen to parallel a decrease in RNA and protein levels. Furthermore, women with high endometrial HAND2 methylation in their premalignant lesions were less likely to respond to progesterone treatment. HAND2 methylation analysis of endometrial secretions collected using high vaginal swabs taken from women with postmenopausal bleeding specifically identified those patients with early stage endometrial cancer with both high sensitivity and high specificity (receiver operating characteristics area under the curve = 0.91 for stage 1A and 0.97 for higher than stage 1A. Finally, mice harbouring a Hand2 knock-out specifically in their endometrium were shown to develop
Ding, Ning; Zhang, Hong; Su, Shan; Ding, Yumei; Yu, Xiaohui; Tang, Yujie; Wang, Qingfang; Liu, Peishu
2017-12-18
Background Endometrial cancer is a common cause of death in gynecological malignancies. Cisplatin is a clinically chemotherapeutic agent. However, drug-resistance is the primary cause of treatment failure. Objective Emodin is commonly used clinically to increase the sensitivity of chemotherapeutic agents, yet whether Emodin promotes the role of Cisplatin in the treatment of endometrial cancer has not been studied. Method CCK-8 kit was utilized to determine the growth of two endometrial cancer cell lines, Ishikawa and HEC-IB. The apoptosis level of Ishikawa and HEC-IB cells was detected by Annexin V / propidium iodide double-staining assay. ROS level was detected by DCFH-DA and NADPH oxidase expression. Expressions of drug-resistant genes were examined by real-time PCR and Western blotting. Results Emodin combined with Cisplatin reduced cell growth and increased the apoptosis of endometrial cancer cells. Co-treatment of Emodin and Cisplatin increased chemosensitivity by inhibiting the expression of drug-resistant genes through reducing the ROS levels in endometrial cancer cells. In an endometrial cancer xenograft murine model, the tumor size was reduced and animal survival time was increased by co-treatment of Emodin and Cisplatin. Conclusion This study demonstrates that Emodin enhances the chemosensitivity of Cisplatin on endometrial cancer by inhibiting ROS-mediated expression of drug-resistance genes. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
Endometrial and acute myeloid leukemia cancer genomes characterized
Two studies from The Cancer Genome Atlas (TCGA) program reveal details about the genomic landscapes of acute myeloid leukemia (AML) and endometrial cancer. Both provide new insights into the molecular underpinnings of these cancers.
Are preoperative histology and MRI useful for classification of endometrial cancer risk?
International Nuclear Information System (INIS)
Body, Noemie; Lavoué, Vincent; De Kerdaniel, Olivier; Foucher, Fabrice; Henno, Sébastien; Cauchois, Aurélie; Laviolle, Bruno; Leblanc, Marc; Levêque, Jean
2016-01-01
The 2010 guidelines of the French National Cancer Institute (INCa) classify patients with endometrial cancer into three risk groups for lymph node invasion and recurrence on the basis of MRI and histological analysis of an endometrial specimen obtained preoperatively. The classification guides therapeutic choices, which may include pelvic and/or para-aortic lymphadenectomy. The purpose of this study was to evaluate the diagnostic performance of preoperative assessment to help identify intermediate- or high-risk patients requiring lymphadenectomy. The study included all patients who underwent surgery for endometrial cancer between January 2010 and December 2013 at either Rennes University Hospital or Vannes Regional Hospital. The criteria for eligibility included a preoperative assessment with MRI and histological examination of an endometrial sample. A histological comparison was made between the preoperative and surgical specimens. Among the 91 patients who underwent a full preoperative assessment, the diagnosis of intermediate- or high-risk endometrial cancer was established by MRI and histology with a sensitivity of 70 %, specificity of 82 %, positive predictive value (PPV) of 87 %, negative predictive value (NPV) of 61 %, positive likelihood ratio (LR+) of 3.8 and negative likelihood ratio (LR-) of 0.3. The risk group was underestimated in 32 % of patients and overestimated in 7 % of patients. MRI underestimated endometrial cancer stage in 20 % of cases, while endometrial sampling underestimated the histological type in 4 % of cases and the grade in 9 % of cases. The preoperative assessment overestimated or underestimated the risk of recurrence in nearly 40 % of cases, with errors in lesion type, grade or stage. Erroneous preoperative risk assessment leads to suboptimal initial surgical management of patients with endometrial cancer
Garuti, Giancarlo; Cellani, Fulvia; Centinaio, Giovanna; Montanari, Giuseppe; Nalli, Giulio; Luerti, Massimo
2006-11-01
A prospective evaluation of the effects on endometrium of third generation aromatase inhibitors (AIs), administered as adjuvant up-front therapy or switched therapy in menopausal patients suffering from breast cancer. Forty-five patients suffering from estrogen-receptor positive breast cancer were treated with AIs as adjuvant endocrine therapy; 27 patients switched from tamoxifen to AIs (group 1) due to adverse medical events related to tamoxifen intake (22 patients) or to an extended endocrine treatment after 60 months of tamoxifen therapy (5 patients); whereas 18 patients received AIs as up-front adjuvant therapy (group 2). All patients underwent endometrial investigation before the start of AIs therapy and, thereafter, at 12 month intervals. Endometrial assessment was based on Transvaginal Ultrasonography (TU), followed by hysteroscopy and endometrial biopsy when a double layered endometrial stripe above 4 mm was measured on the longitudinal plane of uterine scanning. Six patients, showing endometrial hyperplasia before the start of AIs therapy, underwent hysteroscopy on a yearly basis, disregarding the endometrial thickness measured by TU. Histopathologic results on endometrial biopsies represented the reference test in order to estimate the prevalence of endometrial morbidity. Demographic and clinical variables evaluated (age, parity, age at menarche and menopause, Body Mass Index, previous chemotherapy and radiotherapy) did not differ in groups 1 and 2. The average period of endometrial surveillance after the start of AIs therapy was 24.8 +/-10.8 months for group 1 and 21.4 +/- 11.5 months for group 2. A progressive decrease of endometrial thickness, from 8.2 +/- 5.0 to 3.0 +/- 1.2 in group 1 and from 4.7 +/- 4.3 to 1.9 +/- 0.3 in group 2, was found before the start and after 36-48 months of AIs therapy. The second line endometrial investigations' rate dropped from 70.3% to 12.5% in group 1 and from 27.7% to 0.0% in group 2, at baseline and after 36-48 months
RNA-seq Reveals the Overexpression of IGSF9 in Endometrial Cancer
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Zonggao Shi
2018-01-01
Full Text Available We performed RNA-seq on an Illumina platform for 7 patients with endometrioid endometrial carcinoma for which both tumor tissue and adjacent noncancer tissue were available. A total of 66 genes were differentially expressed with significance level at adjusted p value < 0.01. Using the gene functional classification tool in the NIH DAVID bioinformatics resource, 5 genes were found to be the only enriched group out of that list of genes. The gene IGSF9 was chosen for further characterization with immunohistochemical staining of a larger cohort of human endometrioid carcinoma tissues. The expression level of IGSF9 in cancer cells was significantly higher than that in control glandular cells in paired tissue samples from the same patients (p=0.008 or in overall comparison between cancer and the control (p=0.003. IGSF9 expression is higher in patients with myometrium invasion relative to those without invasion (p=0.015. Reanalysis of RNA-seq dataset from The Cancer Genome Atlas shows higher expression of IGSF9 in endometrial cancer versus normal control and expression was associated with poor prognosis. These results suggest IGSF9 as a new biomarker in endometrial cancer and warrant further studies on its function, mechanism of action, and potential clinical utility.
MR staging accuracy for endometrial cancer based on the new FIGO stage
International Nuclear Information System (INIS)
Shin, Kyung Eun; Park, Byung Kwan; Kim, Chan Kyo; Bae, Duk Soo; Song, Sang Yong; Kim, Bohyun
2011-01-01
Background: Magnetic resonance imaging (MRI) has been frequently used to determine a preoperative treatment plan for gynecologic cancers. However, the MR accuracy for staging an endometrial cancer is not satisfactory based on the old FIGO staging system. Purpose: To evaluate MR accuracy for staging endometrial cancer using the new FIGO staging system. Material and Methods: Between January 2005 and May 2009, 199 women underwent surgery due to endometrial cancer. In each patient, an endometrial cancer was staged using MR findings based on the old FIGO staging system and then repeated according to the new FIGO staging system for comparison. Histopathologic findings were used as a standard of reference. Results: The accuracy of MRI in the staging of endometrial carcinoma stage I, II, III, and IV using the old FIGO staging system were 80% (159/199), 89% (178/199), 90% (179/199), and 99% (198/199), respectively, compared to 87% (174/199), 97% (193/199), 90% (179/199), and 99% (198/199), respectively, when using the new FIGO staging criteria. The overall MR accuracy of the old and new staging systems were 51% (101/199) and 81% (161/199), respectively. Conclusion: MRI has become a more useful tool in the preoperative staging of endometrial cancers using the new FIGO staging system compared to the old one with increased accuracy
Lipocalin 2 expression is associated with aggressive features of endometrial cancer
International Nuclear Information System (INIS)
Mannelqvist, Monica; Akslen, Lars A; Stefansson, Ingunn M; Wik, Elisabeth; Kusonmano, Kanthida; Raeder, Maria B; Øyan, Anne M; Kalland, Karl-Henning; Moses, Marsha A; Salvesen, Helga B
2012-01-01
Increased expression of lipocalin 2 (LCN2) has been observed in several cancers. The aim of the present study was to investigate LCN2 in endometrial cancer in relation to clinico-pathologic phenotype, angiogenesis, markers of epithelial-mesenchymal transition (EMT), and patient survival. Immunohistochemical staining was performed using a human LCN2 antibody on a population-based series of endometrial cancer patients collected in Hordaland County (Norway) during 1981-1990 (n = 256). Patients were followed from the time of primary surgery until death or last follow-up in 2007. The median follow-up time for survivors was 17 years. Gene expression data from a prospectively collected endometrial cancer series (n = 76) and a publicly available endometrial cancer series (n = 111) was used for gene correlation studies. Expression of LCN2 protein, found in 49% of the cases, was associated with non-endometrioid histologic type (p = 0.001), nuclear grade 3 (p = 0.001), >50% solid tumor growth (p = 0.001), ER and PR negativity (p = 0.028 and 0.006), and positive EZH2 expression (p < 0.001). LCN2 expression was significantly associated with expression of VEGF-A (p = 0.021), although not with other angiogenesis markers examined (vascular proliferation index, glomeruloid microvascular proliferation, VEGF-C, VEGF-D or bFGF2 expression). Further, LCN2 was not associated with several EMT-related markers (E-cadherin, N-cadherin, P-cadherin, β-catenin), nor with vascular invasion (tumor cells invading lymphatic or blood vessels). Notably, LCN2 was significantly associated with distant tumor recurrences, as well as with the S100A family of metastasis related genes. Patients with tumors showing no LCN2 expression had the best outcome with 81% 5-year survival, compared to 73% for intermediate and 38% for the small subgroup with strong LCN2 staining (p = 0.007). In multivariate analysis, LCN2 expression was an independent prognostic factor in addition to histologic grade and FIGO stage
Endometrial cancer - reduce to the minimum. A new paradigm for adjuvant treatments?
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Scheithauer, Heike R; Schulz, Diana S; Belka, Claus
2011-01-01
Up to now, the role of adjuvant radiation therapy and the extent of lymph node dissection for early stage endometrial cancer are controversial. In order to clarify the current position of the given adjuvant treatment options, a systematic review was performed. Both, Pubmed and ISI Web of Knowledge database were searched using the following keywords and MESH headings: 'Endometrial cancer', 'Endometrial Neoplasms', 'Endometrial Neoplasms/radiotherapy', 'External beam radiation therapy', 'Brachytherapy' and adequate combinations. Recent data from randomized trials indicate that external beam radiation therapy - particularly in combination with extended lymph node dissection - or radical lymph node dissection increases toxicity without any improvement of overall survival rates. Thus, reduced surgical aggressiveness and limitation of radiotherapy to vaginal-vault-brachytherapy only is sufficient for most cases of early stage endometrial cancer
Hormone replacement therapy and the risk of endometrial cancer
DEFF Research Database (Denmark)
Sjögren, Lea L; Mørch, Lina Steinrud; Løkkegaard, Ellen
2016-01-01
BACKGROUND: In 1975, estrogen only was found to be associated with an increased risk of endometrial cancer. In November 2015, NICE guidelines on hormone therapy were published that did not take this risk into account. AIM: This systematic literature review assesses the safety of estrogen plus...... progestin therapy according to the risk of endometrial cancer, while considering both regimen and type of progestin. METHODS: PubMed, EMBASE and the Cochrane Library were searched, resulting in the identification of 527 published articles on menopausal women with intact uteri treated with estrogen only......, estrogen plus progestin or tibolone for a minimum of one year. Risk of endometrial cancer was compared to placebo or never users and measured as relative risk, hazard or odds ratio. RESULTS: 28 studies were included. The observational literature found an increased risk among users of estrogen alone...
Jurczyk, Mieczysława U; Chmaj-Wierzchowska, Karolina; Klofik, Joanna; Sajdak, Stefan; Opala, Tomasz
2013-01-01
Approximately 1 in 20 female cancers in Europe is of the endometrium. Endometrial carcinoma is the most common gynaecologic cancer. Considering the fact that an upward tendency has recently been observed in morbidity due to this type of cancer, this is a serious medical problem. The presented report describes the results of the analysis of selected demographic factors and their effect on the incidence of endometrial cancer. Analysis of the results of treatment of endometrial cancer during 1995-2010 was also an objective of the study. Based on medical records obtained from the HDR Laboratory of Brachytherapy at the Gynaecological & Obstetrics Clinical Hospital, University of Medical Sciences in Poznań, the results of treatment of patients with endometrial cancer by brachytherapy were analyzed. The analysis covered a group of 400 patients. More than a half of the patients completed their education on the level of elementary or secondary school. Taking into consideration the weight of the patients, it appeared that most women had excessive body weight. Most frequently, concomitant hypertension was observed. Moreover, the age at menarche was 12 and 13. Demographic factors exert a significant effect on the incidence of endometrial cancer. 1. Overweight and obesity are important risk factors of endometrial cancer. 2. A strong relationship is observed between the occurrence of hypertension or diabetes, and the development of endometrial cancer. 3. Women who come from the rural environment and continue to live in this environment are more likely to contract endometrial cancer.
Robotic surgery in supermorbidly obese patients with endometrial cancer.
Stephan, Jean-Marie; Goodheart, Michael J; McDonald, Megan; Hansen, Jean; Reyes, Henry D; Button, Anna; Bender, David
2015-07-01
Morbid obesity is a known risk factor for the development of endometrial cancer. Several studies have demonstrated the overall feasibility of robotic-assisted surgical staging for endometrial cancer as well as the benefits of robotics compared with laparotomy. However, there have been few reports that have evaluated robotic surgery for endometrial cancer in the supermorbidly obese population (body mass index [BMI], ≥50 kg/m(2)). We sought to evaluate safety, feasibility, and outcomes for supermorbidly obese patients who undergo robotic surgery for endometrial cancer, compared with patients with lower body mass indices. We performed a retrospective chart review of 168 patients with suspected early-stage endometrial adenocarcinoma who underwent robotic surgery for the management of their disease. Analysis of variance and univariate logistic regression were used to compare patient characteristics and surgical variables across all body weights. Cox proportional hazard regression was used to determine the impact of body weight on recurrence-free and overall survival. The mean BMI of our cohort was 40.9 kg/m(2). Median follow up was 31 months. Fifty-six patients, 30% of which had grade 2 or 3 tumors, were supermorbidly obese with a BMI of ≥50 kg/m(2) (mean, 56.3 kg/m(2)). A comparison between the supermorbidly obese and lower-weight patients demonstrated no differences in terms of length of hospital stay, blood loss, complication rates, numbers of pelvic and paraaortic lymph nodes retrieved, or recurrence and survival. There was a correlation between BMI and conversion to an open procedure, in which the odds of conversion increased with increasing BMI (P = .02). Offering robotic surgery to supermorbidly obese patients with endometrial cancer is a safe and feasible surgical management option. When compared with patients with a lower BMI, the supermorbidly obese patient had a similar outcome, length of hospital stay, blood loss, complications, and numbers of lymph
Banno, Kouji; Kisu, Iori; Yanokura, Megumi; Masuda, Kenta; Ueki, Arisa; Kobayashi, Yusuke; Susumu, Nobuyuki; Aoki, Daisuke
2012-04-01
Endometrial cancer is the seventh most common cancer worldwide among females. An increased incidence and a younger age of patients are also predicted to occur, and therefore elucidation of the pathological mechanisms is important. However, several aspects of the mechanism of carcinogenesis in the endometrium remain unclear. Associations with genetic mutations of cancer-related genes have been shown, but these do not provide a complete explanation. Therefore, epigenetic mechanisms have been examined. Silencing of genes by DNA hypermethylation, hereditary epimutation of DNA mismatch repair genes and regulation of gene expression by miRNAs may underlie carcinogenesis in endometrial cancer. New therapies include targeting epigenetic changes using histone deacetylase inhibitors. Some cases of endometrial cancer may also be hereditary. Thus, patients with Lynch syndrome which is a hereditary disease, have a higher risk for developing endometrial cancer than the general population. Identification of such disease-related genes may contribute to early detection and prevention of endometrial cancer.
Development and validation of prediction models for endometrial cancer in postmenopausal bleeding.
Wong, Alyssa Sze-Wai; Cheung, Chun Wai; Fung, Linda Wen-Ying; Lao, Terence Tzu-Hsi; Mol, Ben Willem J; Sahota, Daljit Singh
2016-08-01
To develop and assess the accuracy of risk prediction models to diagnose endometrial cancer in women having postmenopausal bleeding (PMB). A retrospective cohort study of 4383 women in a One-stop PMB clinic from a university teaching hospital in Hong Kong. Clinical risk factors, transvaginal ultrasonic measurement of endometrial thickness (ET) and endometrial histology were obtained from consecutive women between 2002 and 2013. Two models to predict risk of endometrial cancer were developed and assessed, one based on patient characteristics alone and a second incorporated ET with patient characteristics. Endometrial histology was used as the reference standard. The split-sample internal validation and bootstrapping technique were adopted. The optimal threshold for prediction of endometrial cancer by the final models was determined using a receiver-operating characteristics (ROC) curve and Youden Index. The diagnostic gain was compared to a reference strategy of measuring ET only by comparing the AUC using the Delong test. Out of 4383 women with PMB, 168 (3.8%) were diagnosed with endometrial cancer. ET alone had an area under curve (AUC) of 0.92 (95% confidence intervals [CIs] 0.89-0.94). In the patient characteristics only model, independent predictors of cancer were age at presentation, age at menopause, body mass index, nulliparity and recurrent vaginal bleeding. The AUC and Youdens Index of the patient characteristic only model were respectively 0.73 (95% CI 0.67-0.80) and 0.72 (Sensitivity=66.5%; Specificity=68.9%; +ve LR=2.14; -ve LR=0.49). ET, age at presentation, nulliparity and recurrent vaginal bleeding were independent predictors in the patient characteristics plus ET model. The AUC and Youdens Index of the patient characteristic plus ET model where respectively 0.92 (95% CI 0.88-0.96) and 0.71 (Sensitivity=82.7%; Specificity=88.3%; +ve LR=6.38; -ve LR=0.2). Comparison of AUC indicated that a history alone model was inferior to a model using ET alone
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Koah Vierkoetter
2018-05-01
Full Text Available Patients diagnosed with an endometrial cancer precursor lesion on biopsy may be found to have endometrial cancer at the time of subsequent surgery. The current study seeks to identify patients with endometrial intraepithelial neoplasia (EIN on biopsy that may be harboring an occult carcinoma. Immunohistochemical stains for gene loss of expression (LOE for 6 genes, PTEN, ARID1A, MSH6, MSH2, MLH1, and PMS2, were performed on 113 biopsy specimens with EIN. For the 95 patients with follow-up histology, 40 patients had cancer, 41 had EIN, and 14 had normal endometrium. PTEN LOE was found frequently in both EIN and endometrial cancer, and therefore had low positive predictive value. All specimens with ARID1A, MSH6, MSH2, MLH1, or PMS2 LOE on biopsy were subsequently found to have cancer. LOE of any gene was associated with modest sensitivity (0.78 in identifying patients with endometrial cancer who had EIN on biopsy. Further investigation is warranted to determine if gene LOE is a useful clinical tool when evaluating patients with EIN on biopsy. Keywords: Endometrial intraepithelial neoplasia, Endometrial cancer, Gene expression, PTEN, ARID1A, Mismatch repair genes
A critical assessment on the role of sentinel node mapping in endometrial cancer.
Bogani, Giorgio; Ditto, Antonino; Martinelli, Fabio; Signorelli, Mauro; Perotto, Stefania; Lorusso, Domenica; Raspagliesi, Francesco
2015-10-01
Endometrial cancer is the most common gynecologic malignancy in the developed countries. Although the high incidence of this occurrence no consensus, about the role of retroperitoneal staging, still exists. Growing evidence support the safety and efficacy of sentinel lymph node mapping. This technique is emerging as a new standard for endometrial cancer staging procedures. In the present paper, we discuss the role of sentinel lymph node mapping in endometrial cancer, highlighting the most controversies features.
Dominick, Sally; Hickey, Martha; Chin, Jason; Su, H Irene
2015-12-09
Adjuvant tamoxifen reduces the risk of breast cancer recurrence in women with oestrogen receptor-positive breast cancer. Tamoxifen also increases the risk of postmenopausal bleeding, endometrial polyps, hyperplasia, and endometrial cancer. The levonorgestrel-releasing intrauterine system (LNG-IUS) causes profound endometrial suppression. This systematic review considered the evidence that the LNG-IUS prevents the development of endometrial pathology in women taking tamoxifen as adjuvant endocrine therapy for breast cancer. To determine the effectiveness and safety of levonorgestrel intrauterine system (LNG-IUS) in pre- and postmenopausal women taking adjuvant tamoxifen following breast cancer for the outcomes of endometrial and uterine pathology including abnormal vaginal bleeding or spotting, and secondary breast cancer events. We searched the following databases: Cochrane Menstrual Disorders and Subfertility Group Specialised Register (MDSG), Cochrane Breast Cancer Group Specialised Register (CBCG), Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Database of Abstracts of Reviews of Effects (DARE), The Cochrane Library, clinicaltrials.gov, The World Health Organisation International Trials Registry, ProQuest Dissertations & Theses, MEDLINE, EMBASE, CINAHL (Cumulative Index to Nursing and Allied Health Literature), PsycINFO, Web of Science, OpenGrey, LILACS, PubMed, and Google. The final search was performed in October 2015. Randomised controlled trials of women with breast cancer on adjuvant tamoxifen that compared endometrial surveillance alone (control condition) versus the LNG-IUS with endometrial surveillance (experimental condition) on the incidence of endometrial pathology. Study selection, risk of bias assessment and data extraction were performed independently by two review authors. The primary outcome measure was endometrial pathology (including polyps, endometrial hyperplasia, or endometrial cancer) diagnosed at hysteroscopy or
Project for the National Program of Early Diagnosis of Endometrial Cancer Part I.
Bohîlțea, R E; Ancăr, V; Cirstoiu, M M; Rădoi, V; Bohîlțea, L C; Furtunescu, F
2015-01-01
Endometrial cancer recorded a peak incidence in ages 60-64 years in Romania, reaching in 2013 the average value of 8.06/ 100,000 women, and 15.97/ 100,000 women within the highest risk age range, having in recent years an increasing trend, being higher in urban than in rural population. Annually, approximately 800 new cases are registered in our country. The estimated lifetime risk of a woman to develop endometrial cancer is of about 1,03%. Based on an abnormal uterine bleeding, 35% of the endometrial cancers are diagnosed in an advanced stage of the disease, with significantly diminished lifetime expectancy. Drafting a national program for the early diagnosis of endometrial cancer. We proposed a standardization of the diagnostic steps and focused on 4 key elements for the early diagnosis of endometrial cancer: investigation of abnormal uterine bleeding occurring in pre/ post-menopausal women, investigating features/ anomalies of cervical cytology examination, diagnosis, treatment and proper monitoring of precursor endometrial lesions or cancer associated endometrial lesions and screening high risk populations (Lynch syndrome, Cowden syndrome). Improving medical practice based on diagnostic algorithms addresses the four risk groups, by improving information system reporting and record keeping. Improving addressability cases by increasing the health education of the population will increase the rate of diagnosis of endometrial cancer in the early stages of the disease. ACOG = American Society of Obstetricians and Gynecologists, ASCCP = American Society for Colposcopy and Cervical Pathology, PATT = Partial Activated Thromboplastin Time, BRCA = Breast Cancer Gene, CT = Computerized Tomography, IFGO = International Federation of Gynecology and Obstetrics, HLG = Hemoleucogram, HNPCC = Hereditary Nonpolyposis Colorectal Cancer (Lynch syndrome), IHC = Immunohistochemistry, BMI = Body Mass Index, INR = International Normalized Ratio, MSI = Microsatellites instability, MSI
Subcutaneous metastasis from endometrial cancer; case report and literature review
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Nicolae Bacalbasa
2018-05-01
Full Text Available Subcutaneous metastases from endometrial cancer are rare situations, only few cases being described so far. The main incriminated mechanisms leading to the apparition of such lesions include hematogenous and lymphatic spread. We present the case of a 66-year-old patient known with previous history of stage IIIA endometroid endometrial carcinoma initially treated by surgery and adjuvant chemotherapy who developed at 18 months follow-up a distant subcutaneous oligometastasis. At this time the patient was resubmitted to surgery, the lesion being successfully removed. The histopathological result confirmed the endometrial cancer origin of this lesion. Subcutaneous and cutaneous metastases from endometrial cancer are rare eventualities which are usually diagnosed as part of systemic dissemination of this malignancy; in these cases, the patient is only candidate for oncological treatment with palliative intent. In some cases, in which the lesions occur as oligometastatic disease, surgery might be performed with curative intent. In our case the diagnostic of the subcutaneous lesion as oligometastatic disease transformed the patient in a perfect candidate for curative oncological surgery.
GGC and StuI polymorphism on the androgen receptor gene in endometrial cancer patients
International Nuclear Information System (INIS)
Sasaki, Masahiro; Karube, Akihiro; Karube, Yuko; Watari, Michiko; Sakuragi, Noriaki; Fujimoto, Seiichiro; Dahiya, Rajvir
2005-01-01
Androgens have an anti-proliferative effect on endometrial cells. Human androgen receptor (AR) gene contains two polymorphic short tandem repeats of GGC and CAG, and a single-nucleotide polymorphism on exon 1 that is recognized by the restriction enzyme, StuI. Prior studies have shown that the lengths of the CAG repeat are inversely and linearly related to AR activity and associated with endometrial cancer. However, little is known about the GGC repeat and the StuI polymorphism of the AR gene. Thus, we investigated whether these AR polymorphisms are risk factors for endometrial cancer. To test this hypothesis, the genetic distributions of these polymorphisms were investigated in blood samples from endometrial cancer patients and healthy controls. The allelic and genotyping profiles were analyzed by polymerase chain reaction (PCR), PCR-restriction fragment length polymorphism (PCR-RFLP), and direct DNA sequencing, and analyzed statistically. The GGC repeat was significantly longer in endometrial cancer patients as compared to normal healthy controls. In general, an increased risk of endometrial cancer was found with increasing GGC repeat. The relative risk for the 17 GGC repeat was greater than 4, as compared to controls. However, the StuI polymorphism was not significantly different between patients and controls. The findings suggest that increased numbers of GGC repeat on the AR gene may be a risk factor for endometrial cancer
Potential contribution of the uterine microbiome in the development of endometrial cancer
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Marina R. S. Walther-António
2016-11-01
Full Text Available Abstract Background Endometrial cancer studies have led to a number of well-defined but mechanistically unconnected genetic and environmental risk factors. One of the emerging modulators between environmental triggers and genetic expression is the microbiome. We set out to inquire about the composition of the uterine microbiome and its putative role in endometrial cancer. Methods We undertook a study of the microbiome in samples taken from different locations along the female reproductive tract in patients with endometrial cancer (n = 17, patients with endometrial hyperplasia (endometrial cancer precursor, n = 4, and patients afflicted with benign uterine conditions (n = 10. Vaginal, cervical, Fallopian, ovarian, peritoneal, and urine samples were collected aseptically both in the operating room and the pathology laboratory. DNA extraction was followed by amplification and high-throughput next generation sequencing (MiSeq of the 16S rDNA V3-V5 region to identify the microbiota present. Microbiota data were summarized using both α-diversity to reflect species richness and evenness within bacterial populations and β-diversity to reflect the shared diversity between bacterial populations. Statistical significance was determined through the use of multiple testing, including the generalized mixed-effects model. Results The microbiome sequencing (16S rDNA V3-V5 region revealed that the microbiomes of all organs (vagina, cervix, Fallopian tubes, and ovaries are significantly correlated (p 4.5. Conclusions Our results suggest that the detection of A. vaginae and the identified Porphyromonas sp. in the gynecologic tract combined with a high vaginal pH is statistically associated with the presence of endometrial cancer. Given the documented association of the identified microorganisms with other pathologies, these findings raise the possibility of a microbiome role in the manifestation, etiology, or progression of endometrial cancer that
Prognostic and Clinical Significance of miRNA-205 in Endometrioid Endometrial Cancer.
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Milosz Wilczynski
Full Text Available Endometrial cancer is one of the most common malignancies of the reproductive female tract, with endometrioid endometrial cancer being the most frequent type. Despite the relatively favourable prognosis in cases of endometrial cancer, there is a necessity to evaluate clinical and prognostic utility of new molecular markers. MiRNAs are small, non-coding RNA molecules that take part in RNA silencing and post-transcriptional regulation of gene expression. Altered expression of miRNAs may be associated with cancer initiation, progression and metastatic capabilities. MiRNA-205 seems to be one of the key regulators of gene expression in endometrial cancer. In this study, we investigated clinical and prognostic role of miRNA-205 in endometrioid endometrial cancer. After total RNA extraction from 100 archival formalin-fixed paraffin-embedded tissues, real-time quantitative RT-PCR was used to define miRNA-205 expression levels. The aim of the study was to evaluate miRNA-205 expression levels in regard to patients' clinical and histopathological features, such as: survival rate, recurrence rate, staging, myometrial invasion, grading and lymph nodes involvement. Higher levels of miRNA-205 expression were observed in tumours with less than half of myometrial invasion and non-advanced cancers. Kaplan-Maier analysis revealed that higher levels of miRNA-205 were associated with better overall survival (p = 0,034. These results indicate potential clinical utility of miRNA-205 as a prognostic marker.
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Jane A McElroy
Full Text Available Estrogen-mimicking chemicals, such as cadmium, may be associated with increased susceptibility to hormone-dependent cancers, though supporting data are sparse, particularly for endometrial cancer. The Health and Environmental Exposure Research (HEER study worked with the Arkansas Central Cancer Registry, Iowa Cancer Registry and Missouri Cancer Registry to obtain names of women diagnosed with endometrial cancer who were willing to be contacted for participation in our case control study. Voter registration lists from Iowa and Missouri were used to randomly select similarly aged women as represented in the case population. Participants were interviewed by telephone to obtain information on known or suspected endometrial risk factors. Urine kits were sent to participants for home collection and returned for analysis. Our case-control study consisted of 631 incident cases of endometrial cancer diagnosed from January 2010 to October 2012 and 879 age-matched population-based controls, ages 18-81 years (mean age 65 years. We quantified cadmium amounts in urine and standardized these values through creatinine adjustment. Using data from all survey completers, we developed a multivariable model for endometrial cancer. Creatinine-adjusted cadmium concentration was added to this model. Odds ratio (OR and 95% confidence intervals (CIs for endometrial cancer were calculated. After multivariable adjustment, higher creatinine-adjusted cadmium exposure was associated with a statistically significant increase of endometrial cancer risk (OR: 1.22; 95% CI: 1.03-1.44. Our results provide evidence that cadmium may increase the risk of endometrial cancer, possibly through estrogenic effects.
Emerging molecular-targeted therapies—the challenging case of endometrial cancer
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Ines Vasconcelos
2015-10-01
Full Text Available Endometrial cancer newly affects an estimated 54,870 women in the United States, being responsible for an estimated 10,170 deaths in 2015. It has demonstrated to harbor a complex carcinogenesis process, with limited treatment options for advanced or persistent disease. Identification and targeting of genetic alterations that lead to progressive disease and therapy resistance is not only challenging, but also often does not correlate with a clinical benefit. Targeted maintenance therapies in endometrial cancer have been largely disappointing. Nonetheless, targeted personalized treatment should be the main goal of treatment of advanced disease in the future. Due to the high variety of drugs being tested in early clinical trials, it is hard to keep pace with the latest developments and ongoing trials. This review aims to summarize the latest published and ongoing trials on targeted therapies in endometrial cancer.
Loizzi, V; Cormio, G; Lorusso, M; Latorre, D; Falagario, M; Demitri, P; Scardigno, D; Selvaggi, L E
2014-05-01
The aim of this study was to determine impact of lymph vascular space involvement (LVSI) on recurrence and survival in early stage of endometrial cancer. From 1991 through 2010, all endometrial cancer patients at University Hospital of Bari, Italy were identified. The Log-rank test and Kaplan-Meyer methods were used for time-to-event analysis to evaluate the effects of on lymph vascular space involvement recurrence rate and survival time. Of the 560 endometrial cancer patients, 525 underwent primary surgery. Of those, 399 had early stage disease. Three hundred and forty women were not found to have LVSI, whereas 59 were found to have lymph vascular space involvement. Forty-nine (12%) patients developed a recurrence and 20 of them showed lymph vascular space involvement. The statistical analysis demonstrated that LVSI was strongly associated with a poor survival (P < 0.0001). Lymph vascular space involvement is associated with a high risk of recurrence and poor overall survival in early stage of endometrial cancer; therefore, the clinical decision to decide whether or not a patient with early stage endometrial cancer should receive adjuvant therapy should be included the evaluation of lymph vascular space involvement. © 2013 John Wiley & Sons Ltd.
Endometrial Cancer and Hypermethylation: Regulation of DNA and MicroRNA by Epigenetics
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Kouji Banno
2012-01-01
Full Text Available Endometrial cancer is the seventh most common cancer in women worldwide. Therefore elucidation of the pathogenesis and development of effective treatment for endometrial cancer are important. However, several aspects of the mechanism of carcinogenesis in the endometrium remain unclear. Associations with genetic variation and mutations of cancer-related genes have been shown, but these do not provide a complete explanation. Therefore, in recent years, epigenetic mechanisms that do not involve changes in DNA sequences have been examined. Studies aimed at detection of aberrant DNA hypermethylation in cancer cells present in microscopic amounts in vivo and application of the results to cancer diagnosis have also started. Breakdown of the DNA mismatch repair mechanism is thought to play a large role in the development of endometrial cancer, with changes in the expression of the hMLH1 gene being particularly important. Silencing of genes such as APC and CHFR, Sprouty 2, RASSF1A, GPR54, CDH1, and RSK4 by DNA hypermethylation, onset of Lynch syndrome due to hereditary epimutation of hMLH1 and hMSH2 mismatch repair genes, and regulation of gene expression by microRNAs may also underlie the carcinogenic mechanisms of endometrial cancer. Further understanding of these issues may permit development of new therapies.
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Chiaki Hashimoto
2018-04-01
Full Text Available Endometrial cancer is one of the most common female pelvic cancers and has been considered an androgen-related malignancy. Several studies have demonstrated the anti-cell proliferative effect of androgen on endometrial cancer cells; however, the mechanisms of the anti-cancer effect of androgen remain largely unclear. 17β-hydroxysteroid dehydrogenase type 2 (17β-HSD2, which catalyzes the conversion of E2 to E1, is known to be upregulated by androgen treatment in breast cancer cells. In this study, we therefore focused on the role of androgen on estrogen dependence in endometrial cancer. Dihydrotestosterone (DHT was found to induce 17β-HSD2 mRNA and protein expression in HEC-1B endometrial cancer cells. DHT could also inhibit cell proliferation of HEC-1B when induced by estradiol treatment. In 19 endometrioid endometrial adenocarcinoma (EEA tissues, intratumoral DHT concentration was measured by liquid chromatography/electrospray tandem mass spectrometry and was found to be significantly correlated with 17β-HSD2 immunohistochemical status. We further examined the correlations between 17β-HSD2 immunoreactivity and clinicopathological parameters in 53 EEA tissues. 17β-HSD2 status was inversely associated with the histological grade, clinical stage, and cell proliferation marker Ki-67, and positively correlated with progesterone receptor expression. 17β-HSD2 status tended to be positively associated with androgen receptor status. In 53 EEA cases, the 17β-HSD2-positive group tended to have better prognosis than that for the negative group with respect to progression-free survival and endometrial cancer-specific survival. These findings suggest that androgen suppresses the estrogen dependence of endometrial cancer through the induction of 17β-HSD2 in endometrial cancer.
Zhang, H; Wang, X; Chen, Z; Wang, W
2015-11-30
Endometrial carcinoma (EC) is the most common gynecologic malignancy with increasing morbidity in recent years. MicroRNAs (miRNAs), a type of non-coding RNA, have been proven to be critical in the process of tumorigenesis. miR-424 has been reported to play a protective role in various type of cancer including endometrial carcinoma. It has been reported that high levels of estrogen increase morbidity of EC by promoting cell growth ability. The current research was designed to delineate the mechanism of miR-424 in regulating E2 (17β-estradiol)-induced cell proliferation in endometrial cancer. In this study, we confirmed that cell proliferation is increased significantly in E2-treated endometrial cancer cell lines. Moreover, miR-424 overexpression dramatically decreased E2-induced cell proliferation, indicating a pivotal role in endometrial cancer cell growth. In addition, the results suggest that miR-424 up-regulation inactivated the PI3K/AKT signaling, which was mediated by G-protein-coupled estrogen receptor-1 (GPER) in endometrial cancer. Furthermore, the luciferase report confirmed the targeting reaction between miR-424 and GPER. After transfection with the GPER overexpression vector into E2-induced endometrial cancer cells, we found that GPER significantly attenuated the inhibition effect of miR-424 in E2-induced cell growth in EC. Taken together, our study suggests that increased miR-424 suppresses E2-induced cell growth, and providing a potential therapeutic target for estrogen-associated endometrial carcinoma.
Asyikeen, Wan Adnan Wan Nor; Siti-Azrin, Ab Hamid; Jalil, Nur Asyilla Che; Zin, Anani Aila Mat; Othman, Nor Hayati
2016-11-01
Endometrial cancer is the most common gynaecologic malignancy among females worldwide. The purpose of this study was to determine the median survival time of endometrial cancer patients at the Hospital Universiti Sains Malaysia (USM). A list of 121 endometrial cancer cases registered at Hospital USM between 2000 until 2011 was retrospectively reviewed. The survival time of the endometrial cancer patients was estimated by Kaplan-Meier survival analysis. Log-rank tests were performed to compare the survival of the patients based on socio-demographics and clinical presentation. Only 108 patients, 87.0%, were included who were of Malay ethnicity. Previous history included menopause in 67.6% of patients and diabetes mellitus in 39.8% of patients; additionally, 63.4% of patients were nulliparous. Tumour staging was as follows: 24.5% stage I, 10.8% stage II, 26.5% stage III and 38.2% stage IV. The overall median survival time of the endometrial cancer patients was 70.20 months (95% confidence interval (CI): 51.79, 88.61). The significant factors were age, the presence of lymphovascular invasion and treatment received. The overall survival of endometrial cancer was low. A prospective study needs to be carried out to discover more effective and accurate tests for the early detection of endometrial cancer.
Estrogen receptor alpha gene polymorphism and endometrial cancer risk – a case-control study
International Nuclear Information System (INIS)
Wedrén, Sara; Stiger, Fredrik; Persson, Ingemar; Baron, John A; Weiderpass, Elisabete; Lovmar, Lovisa; Humphreys, Keith; Magnusson, Cecilia; Melhus, Håkan; Syvänen, Ann-Christine; Kindmark, Andreas; Landegren, Ulf; Fermér, Maria Lagerström
2008-01-01
Estrogen is an established endometrial carcinogen. One of the most important mediators of estrogenic action is the estrogen receptor alpha. We have investigated whether polymorphic variation in the estrogen receptor alpha gene (ESR1) is associated with endometrial cancer risk. In 702 cases with invasive endometrial cancer and 1563 controls, we genotyped five markers in ESR1 and used logistic regression models to estimate odds ratios (OR) and 95 percent confidence intervals (CI). We found an association between rs2234670, rs2234693, as well as rs9340799, markers in strong linkage disequilibrium (LD), and endometrial cancer risk. The association with rs9340799 was the strongest, OR 0.75 (CI 0.60–0.93) for heterozygous and OR 0.53 (CI 0.37–0.77) for homozygous rare compared to those homozygous for the most common allele. Haplotype models did not fit better to the data than single marker models. We found that intronic variation in ESR1 was associated with endometrial cancer risk
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Lianlian Wang
2015-07-01
Full Text Available Quantification of the association between breastfeeding and risk of endometrial cancer is still conflicting. We therefore conducted a meta-analysis to assess the association between breastfeeding and endometrial cancer risk. Pertinent studies were identified by a search of PubMed and Web of Knowledge through April 2015. A random effect model was used to combine the data for analysis. Sensitivity analysis and publication bias were conducted. Dose-response relationships were assessed by restricted cubic spline and variance-weighted least squares regression analysis. Fourteen articles involving 5158 endometrial cancer cases and 706,946 participants were included in this meta-analysis. Pooled results suggested that breastfeeding significantly reduced the risk of endometrial cancer (summary relative risk (RR: 0.77, 95% CI: 0.62–0.96, I2: 63.0%, especially in North America (summary RR: 0.87, 95% CI: 0.79–0.95. A linear dose-response relationship was found, with the risk of endometrial cancer decreased by 2% for every one-month increase in the duration of breastfeeding (summary RR: 0.98, 95% CI: 0.97–0.99. Our analysis suggested that breastfeeding, particularly a longer duration of breastfeeding, was inversely associated with the risk of endometrial cancer, especially in North America, but not in Europe and Asia, probably due to the small number of cases included. Due to this limitation, further studies originating in other countries are required to assess the association between breastfeeding and endometrial cancer risk.
Prognostic value of tumour endothelial markers in patients with endometrial cancer
BERSINGER, NICK A.; SCHNEIDER, BRIGITTE; VORBURGER, STEPHAN A.; JOHANN, SILKE; CANDINAS, DANIEL; MUELLER, MICHAEL D.
2010-01-01
Endometrial cancer is one of the more frequent and most lethal gynaecological cancer types. Since it occurs more frequently in elderly and overweight patients, a pre-operative staging method would be beneficial. The growth of solid neoplasms is always accompanied by neovascularisation. Tumour endothelial markers (TEMs) are a group of recently described endothelial cell surface markers that appear to be specific to neoplastic tissue. This study aimed to investigate the potential usefulness of TEM assessment in the endometrium by comparing the transcriptional expression of TEMs in the normal endometrium with endometroid adenocarcinoma tissue. Tissues were lysed and the RNA was extracted, assessed and reverse transcribed in one batch. Real-time quantitative PCR was performed for TEM-1, -2, -6, -7, -7r and -8. GAPDH, β-actin and ribosomal protein L13A (RPL13A) were used as control genes. TEM-8 showed the highest expression level in all of the groups. TEM-1 showed higher expression levels in the normal endometrium than in the tumour tissues. For the remaining TEMs, we found a higher expression in the cancer samples than in the normal endometria. Statistical significance of this difference was achieved for TEM-1, -2 and-7. No clear correlation was noted between the tumour stage and the level of TEM-1, -6 and -8 expression. Apart from TEM-6, the highest expression in FIGO I cancer stages was noted in the remaining TEMs. Our results showed that for most of these tumour endothelial markers, gene expression was slightly higher in the endometrial carcinoma tissue samples than in the endometrium of normal cycling women. However, with the possible exception of TEM-8 and -6, absolute expression levels were generally low, indicating that most TEMs may only be specifically expressed in a restricted number of cancer types (e.g., colorectal). Therefore, TEMs may not be useful in the context of endometrial cancer. PMID:22966283
Prognostic value of tumour endothelial markers in patients with endometrial cancer.
Bersinger, Nick A; Schneider, Brigitte; Vorburger, Stephan A; Johann, Silke; Candinas, Daniel; Mueller, Michael D
2010-01-01
Endometrial cancer is one of the more frequent and most lethal gynaecological cancer types. Since it occurs more frequently in elderly and overweight patients, a pre-operative staging method would be beneficial. The growth of solid neoplasms is always accompanied by neovascularisation. Tumour endothelial markers (TEMs) are a group of recently described endothelial cell surface markers that appear to be specific to neoplastic tissue. This study aimed to investigate the potential usefulness of TEM assessment in the endometrium by comparing the transcriptional expression of TEMs in the normal endometrium with endometroid adenocarcinoma tissue. Tissues were lysed and the RNA was extracted, assessed and reverse transcribed in one batch. Real-time quantitative PCR was performed for TEM-1, -2, -6, -7, -7r and -8. GAPDH, β-actin and ribosomal protein L13A (RPL13A) were used as control genes. TEM-8 showed the highest expression level in all of the groups. TEM-1 showed higher expression levels in the normal endometrium than in the tumour tissues. For the remaining TEMs, we found a higher expression in the cancer samples than in the normal endometria. Statistical significance of this difference was achieved for TEM-1, -2 and-7. No clear correlation was noted between the tumour stage and the level of TEM-1, -6 and -8 expression. Apart from TEM-6, the highest expression in FIGO I cancer stages was noted in the remaining TEMs. Our results showed that for most of these tumour endothelial markers, gene expression was slightly higher in the endometrial carcinoma tissue samples than in the endometrium of normal cycling women. However, with the possible exception of TEM-8 and -6, absolute expression levels were generally low, indicating that most TEMs may only be specifically expressed in a restricted number of cancer types (e.g., colorectal). Therefore, TEMs may not be useful in the context of endometrial cancer.
Clinical importance of serum HE4 and MMP2 levels in endometrial cancer patients
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Cymbaluk-Ploska A
2017-06-01
Full Text Available Aneta Cymbaluk-Płoska,1 Anita Chudecka-Głaz,1 Ewa Pius-Sadowska,2 Agnieszka Sompolska-Rzechuła,3 Bogusław Machaliński,2 Anna Surowiec,1 Janusz Menkiszak1 1Department of Gynecological Surgery and Gynecological Oncology of Adults and Adolescents, 2Department of General Pathology, Pomeranian Medical University, 3Department of Statistics, West Pomeranian University of Technology, Szczecin, Poland Introduction: Endometrial cancer is the one of the most common cancers of the genital organ. HE4 and MMP2 are both proteins whose serum levels increase in endometrial cancer.Aim: To explore the diagnostic potential of the serum levels of HE4 and MMP2 in patients with endometrial cancer and benign endometrial diseases. To assess the relationship between the serum levels of HE4 and MMP2 and the typical prognostic factors in patients with endometrial cancer.Materials and methods: Included in the study was a group of 112 patients presenting with bleeding abnormalities at the Pomeranian Medical University in years 2012–2016. Serum HE4 concentrations were measured using the Elecsys Electrochemiluminescence Immunoassay (ECLIA. MMP2 concentrations were quantified in the serum using multiplex immunoassays.Results: We observed statistically significant differences in mean serum levels of HE4 and MMP2 between the group of endometrial cancer patients and the group of patients with no changes in the endometrium (P=0.002/0.003. The diagnostic potential of HE4 and MMP2 in differentiation of high (International Federation of Gynecology and Obstetrics [FIGO] III and IV vs low (FIGO I and II clinical stage of tumor and prediction of cellular differentiation grade (G1 vs G3 on the basis of the analysis of the area under the curve is, respectively, 0.86 and 0.82 for HE4 and 0.82 and 0.74 for MMP2. The HE4 marker was significantly more specific than MMP2 in every study group and amounted to 93% vs 86% in all patients included in the analysis, 94% vs 84% in pre
Impact of robotics on the outcome of elderly patients with endometrial cancer.
Lavoue, Vincent; Zeng, Xing; Lau, Susie; Press, Joshua Z; Abitbol, Jeremie; Gotlieb, Raphael; How, Jeffrey; Wang, Yifan; Gotlieb, Walter H
2014-06-01
To evaluate the impact of introducing a robotics program on clinical outcome of elderly patients with endometrial cancer. Evaluation and comparison of peri-operative morbidity and disease-free interval in 163 consecutive elderly patients (≥70years) with endometrial cancer undergoing staging procedure with traditional open surgery compared to robotic surgery. All consecutive patients ≥70years of age with endometrial cancer who underwent robotic surgery (n=113) were compared with all consecutive patients ≥70years of age (n=50) before the introduction of a robotic program in December 2007. Baseline patient characteristics were similar in both eras. Patients undergoing robotic surgery had longer mean operating times (244 compared with 217minutes, p=0.009) but fewer minor adverse events (17% compared with 60%, probotics cohort had less estimated mean blood loss (75 vs 334mL, probotics program for the treatment of endometrial cancer in the elderly has significant benefits, including lower minor complication rate, less operative blood loss and shorter hospitalization without compromising 2-year disease-free survival. Copyright © 2014 Elsevier Inc. All rights reserved.
Polycystic ovary syndrome and risk of endometrial, ovarian, and breast cancer: a systematic review.
Harris, Holly R; Terry, Kathryn L
2016-01-01
Polycystic ovary syndrome (PCOS) is a complex endocrine disorder with an estimated prevalence of 4-21% in reproductive aged women. The altered metabolic and hormonal environment among women with PCOS may increase their risk of some types of cancer. We performed a comprehensive review of the literature using numerous search terms for all studies examining the associations between polycystic ovary syndrome and related characteristics and cancer published in English through October 2016. This review summarizes the epidemiological findings on the associations between PCOS and endometrial, ovarian, and breast cancers and discusses the methodological issues, complexities, and underlying mechanisms of these associations. We identified 11 individual studies and 3 meta-analyses on the associations between PCOS and endometrial cancer, 8 studies and 1 meta-analysis for ovarian cancer, and 10 studies and 1 meta-analysis for breast cancer. Multiple studies reported that women with PCOS were at a higher risk for endometrial cancer; however, many did not take into account body mass index (BMI), a strong and well-established risk factor for endometrial cancer. The association with ovarian cancer was less clear, but a potentially increased risk of the borderline serous subtype was reported by two studies. No consistent association between PCOS risk and breast cancer was observed. The associations between PCOS and endometrial, ovarian, and breast cancer are complex, with the need to consider many methodological issues in future analyses. Larger well-designed studies, or pooled analyses, may help clarify these complex associations.
Lu, Karen H; Loose, David S; Yates, Melinda S; Nogueras-Gonzalez, Graciela M; Munsell, Mark F; Chen, Lee-May; Lynch, Henry; Cornelison, Terri; Boyd-Rogers, Stephanie; Rubin, Mary; Daniels, Molly S; Conrad, Peggy; Milbourne, Andrea; Gershenson, David M; Broaddus, Russell R
2013-08-01
Women with Lynch syndrome have a 40% to 60% lifetime risk for developing endometrial cancer, a cancer associated with estrogen imbalance. The molecular basis for endometrial-specific tumorigenesis is unclear. Progestins inhibit estrogen-driven proliferation, and epidemiologic studies have shown that progestin-containing oral contraceptives (OCP) reduce the risk of endometrial cancer by 50% in women at general population risk. It is unknown whether they are effective in women with Lynch syndrome. Asymptomatic women ages 25 to 50 with Lynch syndrome were randomized to receive the progestin compounds Depo-Provera (depo-MPA) or OCP for three months. An endometrial biopsy and transvaginal ultrasound were conducted before and after treatment. Endometrial proliferation was evaluated as the primary endpoint. Histology and a panel of surrogate endpoint biomarkers were evaluated for each endometrial biopsy as secondary endpoints. A total of 51 women were enrolled, and 46 completed treatment. Two of the 51 women had complex hyperplasia with atypia at the baseline endometrial biopsy and were excluded from the study. Overall, both depo-MPA and OCP induced a dramatic decrease in endometrial epithelial proliferation and microscopic changes in the endometrium characteristic of progestin action. Transvaginal ultrasound measurement of endometrial stripe was not a useful measure of endometrial response or baseline hyperplasia. These results show that women with Lynch syndrome do show an endometrial response to short-term exogenous progestins, suggesting that OCP and depo-MPA may be reasonable chemopreventive agents in this high-risk patient population.
Synchronous primary ovarian and endometrial cancers: a series of cases and a review of literature
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Sylwia Dębska-Szmich
2014-03-01
Full Text Available Synchronous cancers account for 0.7-1.8% of all gynecologic cancers. Among them, synchronous ovarian and endometrial cancers are predominant (40-53%. Patients with synchronous cancers have better prognosis than those with single disseminated cancer. We present 10 patients with synchronous ovarian and endometrial cancers who were treated at the Chemotherapy Department of the Medical University of Lodz in 2009-2013. The most often reported symptom of the disease was abnormal vaginal bleeding (6 patients. The range of the patients’ age was 48-62 and the median age was 56. Five patients had stage I of ovarian cancer, single patients had stage IIA, IIB and IIIB, 2 patients had stage IIIC. Three patients had I, 5 – II, and 2 – III stage of endometrial cancer. All patients had endometrioid type of endometrial cancer, 7 of them had also the same histological type of ovarian cancer. All patients had adjuvant chemotherapy because of ovarian cancer, none of them had adjuvant radiotherapy. One patient was lost to follow up. For other patients a median follow up was 13 months (range: 3-53 months. One patient experienced relapse, all patients are alive. Synchronous ovarian and endometrial cancers are usually diagnosed at an earlier stage, have lower histological grade and better prognosis than single cancers. The most common histological type of both endometrial and ovarian cancers is endometrioid carcinoma. The first symptoms reported by our patients and the course of the disease were concordant with data from the literature.
Ballard, Karen S; Homesley, Howard D; Hodson, Charles; Presant, Cary A; Rutledge, James; Hallquist, Allan; Perree, Mathieu
2010-03-01
The in vitro microculture kinetic (MiCK) apoptosis assay has been used to predict single or combination chemotherapy response in leukemia patients. This feasibility study addressed MiCK in endometrial cancer specimens. Endometrial cancer specimens from total abdominal hysterectomies were processed at a central laboratory. Single cell suspensions of viable endometrial cancer cells were plated in individual wells. Single and combination regimens were tested: combinations of doxorubicin, cisplatin, and paclitaxel and carboplatin and paclitaxel (Gynecologic Oncology Group [GOG] 209 endometrial cancer phase III trial arms) as well as single agent testing with paclitaxel, carboplatin, doxorubicin, cisplatin, ifosfamide, and vincristine (active agents in GOG trials). Apoptosis was measured continuously over 48 hours. Fifteen of nineteen patients had successful assays. The highest mean chemo sensitivity was noted in the combination of cisplatin, doxorubicin, and paclitaxel with lower mean chemosensitivity for carboplatin and paclitaxel. Combination chemotherapy had higher chemosensitivity than single drug chemotherapy. However, in 25% of patients a single drug had higher chemosensitivity than combination chemotherapy. As single agents, ifosfamide, cisplatin, and paclitaxel had the highest kinetic unit values. Using a panel of agents simulating clinical dose regimens, the MiCK assay was feasible in evaluating in vitro chemosensitivity of endometrial cancer. MiCK assay results correlated with GOG clinical trial results. However, 25% of patients might be best treated with single agent chemotherapy selected by MiCK. Ifosfamide, cisplatin, and paclitaxel appear to have high activity as single agents. MiCK may be useful in future new drug testing and individualizing endometrial cancer patient's chemotherapy management.
Epidemiology of Endometrial Cancer Consortium (E2C2)
The Epidemiology of Endometrial Cancer Consortium studies the etiology of this common cancer and build on resources from existing studies by combining data across studies in order to advance the understanding of the etiology of this disease.
Arem, H; Gunter, M J; Cross, A J; Hollenbeck, A R; Sinha, R
2013-08-06
There are limited prospective studies of fish and meat intakes with risk of endometrial cancer and findings are inconsistent. We studied associations between fish and meat intakes and endometrial cancer incidence in the large, prospective National Institutes of Health-AARP Diet and Health Study. Intakes of meat mutagens 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and benzo(a)pyrene (BaP) were also calculated. We used Cox proportional hazards regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). We observed no associations with endometrial cancer risk comparing the highest to lowest intake quintiles of red (HR=0.91, 95% CI 0.77-1.08), white (0.98, 0.83-1.17), processed meats (1.02, 0.86-1.21) and fish (1.10, 95% CI 0.93-1.29). We also found no associations between meat mutagen intakes and endometrial cancer. Our findings do not support an association between meat or fish intakes or meat mutagens and endometrial cancer.
Psychosocial factors and mortality in women with early stage endometrial cancer.
Telepak, Laura C; Jensen, Sally E; Dodd, Stacy M; Morgan, Linda S; Pereira, Deidre B
2014-11-01
Psychosocial factors have previously been linked with survival and mortality in cancer populations. Little evidence is available about the relationship between these factors and outcomes in gynaecologic cancer populations, particularly endometrial cancer, the fourth most common cancer among women. This study examined the relationship between several psychosocial factors prior to surgical resection and risk of all-cause mortality in women with endometrial cancer. The study utilized a non-experimental, longitudinal design. Participants were 87 women (Mage = 60.69 years, SDage = 9.12 years) who were diagnosed with T1N0-T3N2 endometrial cancer and subsequently underwent surgery. Participants provided psychosocial data immediately prior to surgery. Survival statuses 4-5 years post-diagnoses were abstracted via medical record review. Cox regression was employed for the survival analysis. Of the 87 women in this sample, 21 women died during the 4- to 5-year follow-up. Adjusting for age, presence of regional disease and medical comorbidity severity (known biomedical prognostic factors), greater use of an active coping style prior to surgery was significantly associated with a lower probability of all-cause mortality, hazard ratio (HR) = 0.78, p = .04. Life stress, depressive symptoms, use of self-distraction coping, receipt of emotional support and endometrial cancer quality of life prior to surgery were not significantly associated with all-cause mortality 4-5 years following diagnosis. Greater use of active coping prior to surgery for suspected endometrial cancer is associated with lower probability of all-cause mortality 4-5 years post-surgery. Future research should attempt to replicate these relationships in a larger and more representative sample and examine potential behavioural and neuroendocrine/immune mediators of this relationship. What is already known on this subject? Psychosocial factors have previously been linked with clinical outcomes in a
Combined colonoscopy and endometrial biopsy cancer screening results in women with Lynch syndrome.
Nebgen, Denise R; Lu, Karen H; Rimes, Sue; Keeler, Elizabeth; Broaddus, Russell; Munsell, Mark F; Lynch, Patrick M
2014-10-01
Endometrial biopsy (EMBx) and colonoscopy performed under the same sedation is termed combined screening and has been shown to be feasible and to provide a less painful and more satisfactory experience for women with Lynch syndrome (LS). However, clinical results of these screening efforts have not been reported. The purpose of this study was to evaluate the long-term clinical outcomes and patient compliance with serial screenings over the last 10.5 years. We retrospectively analyzed the data for 55 women with LS who underwent combined screening every 1-2 years between 2002 and 2013. Colonoscopy and endometrial biopsy were performed by a gastroenterologist and a gynecologist, with the patient under conscious sedation. Out of 111 screening visits in these 55 patients, endometrial biopsies detected one simple hyperplasia, three complex hyperplasia, and one endometrioid adenocarcinoma (FIGO Stage 1A). Seventy-one colorectal polyps were removed in 29 patients, of which 29 were tubular adenomas. EMBx in our study detected endometrial cancer in 0.9% (1/111) of surveillance visits, and premalignant hyperplasia in 3.6% (4/111) of screening visits. No interval endometrial or colorectal cancers were detected. Combined screening under sedation is feasible and less painful than EMBx alone. Our endometrial pathology detection rates were comparable to yearly screening studies. Our results indicate that screening of asymptomatic LS women with EMBx every 1-2 years, rather than annually, is effective in the early detection of (pre)cancerous lesions, leading to their prompt definitive management, and potential reduction in endometrial cancer. Copyright © 2014 Elsevier Inc. All rights reserved.
Survival after relapse in patients with endometrial cancer : results from a randomized trial
Creutzberg, CL; van Putten, WLJ; Koper, PC; Lybeert, MLM; Jobsen, JJ; Warlam-Rodenhuis, CC; De Winter, KAJ; Lutgens, LCHW; van den Bergh, ACM; van der Steen-Banasik, E; Beerman, H; van Lent, M
Objective. The aim of this study was to determine the rates of local control and survival after relapse in patients with stage I endometrial cancer treated in the multicenter randomized PORTEC trial. Methods, The PORTEC trial included 715 patients with stage I endometrial cancer, either grade I or 2
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Henrica M J Werner
Full Text Available Stathmin is a prognostic marker in many cancers, including endometrial cancer. Preclinical studies, predominantly in breast cancer, have suggested that stathmin may additionally be a predictive marker for response to paclitaxel. We first evaluated the response to paclitaxel in endometrial cancer cell lines before and after stathmin knock-down. Subsequently we investigated the clinical response to paclitaxel containing chemotherapy in metastatic endometrial cancer in relation to stathmin protein level in tumors. Stathmin level was also determined in metastatic lesions, analyzing changes in biomarker status on disease progression. Knock-down of stathmin improved sensitivity to paclitaxel in endometrial carcinoma cell lines with both naturally higher and lower sensitivity to paclitaxel. In clinical samples, high stathmin level was demonstrated to be associated with poor response to paclitaxel containing chemotherapy and to reduced disease specific survival only in patients treated with such combination. Stathmin level increased significantly from primary to metastatic lesions. This study suggests, supported by both preclinical and clinical data, that stathmin could be a predictive biomarker for response to paclitaxel treatment in endometrial cancer. Re-assessment of stathmin level in metastatic lesions prior to treatment start may be relevant. Also, validation in a randomized clinical trial will be important.
International Nuclear Information System (INIS)
Warenczak-Florczak, Z.; Roszak, A.; Wlodarczyk, H.; Wojciechowska-Lacka, A.
2011-01-01
Background: In case of pure prognostic factors women with cervical and endometrial cancer after surgical operation need to be treated with radiotherapy . Every radiation treatment may be involved with toxicity, acute and late. Material and methods: Performed was detailed analysis of 173 patients with cervical (38) and endometrial (135) cancer. We evaluated early and late post radiation reactions in all patients. Results: Acute reactions were found in 48.5% and late toxicity was found in 9.8% of patients. Women with endometrial cancer were significantly older then patients with cervical cancer (p < 0.002). Higher percentage of acute and late toxicity was observed from the bowel tah urinary tract (26% and 22.5% - acute; 8.1% and 1.73% - late). Higher percentage of acute side effects was observed in patients with cervical than with endometrial cancer (60.5% and 33.7%). Late post radiation reaction predominate also in patient with cervical cancer (13.2% and 8.9%). The adverse effects were associated with prolonged time of treatment due to breaks in radiotherapy. Higher percentage of breaks was found in older patients, more frequent in patient with endometrial than in cervical cancer group (7.4% and 2.6%).To conclude early postradiation reaction appeared more frequently, than late post radiation reactions. It was stated that early and late post radiation reaction appear more frequently in women with cervical than in endometrial cancer. Interruption in radiation delivery was longer than seven days in group with endometrial cancer that leads to extension of complete radiation treatment. (authors)
Endogenous estrogens and the risk of breast, endometrial, and ovarian cancers.
Brown, Susan B; Hankinson, Susan E
2015-07-01
Data from laboratory and epidemiologic studies support a relationship between endogenous hormones and the increased risk of several female cancers. In epidemiologic studies, consistent associations have been observed between risk of breast, ovarian and endometrial cancers and reproductive and hormonal risk factors such as high postmenopausal body mass index (BMI) and postmenopausal hormone use, which suggest the importance of endogenous hormones in the etiology of these diseases. The relationship between circulating estrogen levels in postmenopausal women and the risk of breast cancer is well established, with an approximately 2-fold higher risk among women in the top 20-25% (versus bottom 20-25%) of levels. However, data evaluating the relationship between endogenous estrogens and premenopausal breast cancer risk are more limited and less consistent. Two studies to date have evaluated the relationship between circulating estrogens and breast cancer risk by menstrual cycle phase at blood collection and only one study has examined this relationship by menopausal status at diagnosis. Three prospective studies have evaluated circulating estrogen levels and endometrial cancer risk in postmenopausal women, with consistent strong positive associations reported (with relative risks of 2-4 comparing high versus low hormone levels), while this relationship has not been studied in premenopausal women. Compared to breast and endometrial cancers, reproductive and hormonal characteristics such as postmenopausal hormone use are generally weaker and less consistent risk factors for ovarian cancer, and the only small prospective study conducted to date indicated a non-significant positive relationship between circulating estrogen levels and ovarian cancer risk. In this review, we summarize current evidence and identify key areas to be addressed in future epidemiologic studies of endogenous estrogens and the risk of breast, endometrial, and ovarian cancers. Copyright © 2015
Vaginal vault recurrences of endometrial cancer in non-irradiated patients
DEFF Research Database (Denmark)
Hardarson, Hordur Alexander; Nyhøj Heidemann, Lene; Christensen, René dePont
2015-01-01
are few and limited to previously irradiated patients or patients with advanced disease. Investigation of surgical treatment for isolated vaginal vault recurrence is practically nonexistent. The aim of this study is to evaluate the efficacy of RT and ST in a non-irradiated group with recurrent endometrial...... cancer limited to the vaginal vault. METHODS: Patients treated for recurrent endometrial cancer at Odense University Hospital, Denmark between 2003 and 2012 were identified, n = 118. Thirty-three patients had an isolated vaginal vault recurrence and were treated with either RT, ST or both. Re...
Childhood body mass index and height and risk of histologic subtypes of endometrial cancer
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Aarestrup, J.; Gamborg, M.; Ulrich, L. G.
2016-01-01
BACKGROUND: Endometrial cancer risk factors include adult obesity and taller stature, but the influence of size earlier in life is incompletely understood. We examined whether childhood body mass index (BMI; kg m(-2)) and height were associated with histologic subtypes of endometrial cancer...
Dieli-Conwright, C M; Ma, H; Lacey, J V; Henderson, K D; Neuhausen, S; Horn-Ross, P L; Deapen, D; Sullivan-Halley, J; Bernstein, L
2013-08-06
Physical activity may be associated with decreasing endometrial cancer risk; it remains unclear whether the association is modified by body size. Among 93 888 eligible California Teachers Study participants, 976 were diagnosed with incident endometrial cancer between 1995-1996 and 2007. Cox proportional hazards regression methods were used to estimate relative risks (RRs) and 95% confidence intervals (CIs) for endometrial cancer associated with long-term (high school through age 54 years) and baseline (3 years prior to joining the cohort) strenuous and moderate recreational physical activity, overall and by body size. Increased baseline strenuous recreational physical activity was associated with decreased endometrial cancer risk (Ptrend=0.006) with approximately 25% lower risk among women exercising >3 h per week per year than among those exercising activity was associated with lower risk among overweight/obese women. Increasing physical activity, particularly strenuous activity, may be a lifestyle change that overweight and obese women can implement to reduce their endometrial cancer risk.
Faber, Mette Tuxen; Frederiksen, Kirsten; Jensen, Allan; Aarslev, Peter Bo; Kjaer, Susanne K
2017-08-01
To investigate time trends in the incidence of overall, type 1 and type 2 endometrial cancer in Denmark 1978-2014, correcting for hysterectomy. Based on the Danish Cancer Registry and the Danish National Patient Registry we calculated hysterectomy-corrected incidence rates of overall, type 1 and type 2 endometrial cancer. Separate analyses for women incidence with 95% confidence intervals (CI). The overall incidence of endometrial cancer decreased slightly from 1978 to 1995, but in the last two decades of the study period the incidence has been stable (APC=0.16; 95% CI: -0.19; 0.50). In the study period (1978-2014) type 1 endometrial cancer incidence decreased slightly (APC=-0.67; 95% CI:-0.83; -0.52), whereas the incidence of type 2 endometrial cancer increased substantially (APC=4.85; 95% CI: 4.47; 5.23). The decrease in type 1 endometrial cancer was most pronounced before 1996 in women younger than 55 years (APC=-2.79; 95% CI: -3.65; -1.91), while the largest increase in type 2 endometrial cancer was observed after 1996 (APC=6.42; 95% CI: 5.72; 7.12). Over a period of more than 35 years, the incidence of type 1 endometrial cancer decreased, mainly in pre- and perimenopausal women, while type 2 endometrial cancer incidence increased. Copyright © 2017 Elsevier Inc. All rights reserved.
FOXP1 forkhead transcription factor is associated with the pathogenesis of endometrial cancer
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Makito Mizunuma
2016-05-01
Full Text Available Endometrial cancers are mostly estrogen-dependent. FOXP1 is a P subfamily of forkhead box (FOX, and known as an estrogen-responsive transcription factor. The aims of this study were to examine histological location of FOXP1 in normal and malignant endometrium, and to investigate a possible association between FOXP1 and other factors considered to be involved in pathogenesis of endometrial cancer. The levels of FOXP1, estrogen receptor (ERα, and ERβ expression were examined immunohistochemically in normal and malignant endometrium obtained from 75 women (8 normal, 8 atypical endometrial hyperplasia, and 59 endometrial cancers from grade 1 to 3. The effects of estrogen on ERα, FOXP1, KRAS, and PTEN expression were analyzed in telomerase-immortalized human endometrial stromal cells (T HESCs by Western blotting. Western blotting was also used to examine the effect of FOXP1 plasmid DNA or siRNA transfection on KRAS and PTEN expression in Ishikawa cells (well differentiated endometrioid adenocarcinoma, HEC-50B cells (poorly differentiated endometrioid adenocarcinoma, and T HESCs, respectively. FOXP1 was expressed in normal and malignant endometrium, but the rate of expression was different depending upon menstrual cycle and pathological grade of malignancy. FOXP1 expression in nucleus and cytoplasm of grade 3 endometrioid cancers was significantly lower than that of grade 1 and 2 ones. Estradiol increased levels of FOXP1 and KRAS expression in a dose- and time-dependent manner in T HESCs cells, and FOXP1 transfection or knockdown led to increase or decrease of KRAS expression but not PTEN. KRAS expression level was significantly related to FOXP1 and ERα levels in cancer tissues. Estradiol did not affect KRAS expression in T HESCs cells transfected with FOXP1 siRNA. These results suggest that FOXP1 is involved in estrogen dependent endometrial cancers through KRAS pathway.
Greimel, Elfriede; Nordin, Andy; Lanceley, Anne; Creutzberg, Carien L; van de Poll-Franse, Lonneke V; Radisic, Vesna Bjelic; Galalae, Razvan; Schmalz, Claudia; Barlow, Ellen; Jensen, Pernille T; Waldenström, Ann-Charlotte; Bergmark, Karin; Chie, Wei-Chu; Kuljanic, Karin; Costantini, Anna; Singer, Susanne; Koensgen, Dominique; Menon, Usha; Daghofer, Fedor
2011-01-01
A validation study was conducted to evaluate the psychometric properties of the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Endometrial Cancer Module (EORTC QLQ-EN24). This module was designed to assess disease and treatment specific aspects of the quality of life (QoL) of patients with endometrial cancer. Two hundred and sixty-eight women with endometrial cancer were recruited in different phases of treatment: after pelvic surgery (Group 1); during adjuvant chemotherapy and/or radiotherapy (Group 2); after completion of treatment (Group 3). Patients completed the EORTC QLQ-C30, the endometrial cancer module and a short debriefing questionnaire. Multi-trait scaling analyses confirmed the hypothesised scale structure of the QLQ-EN24. Internal consistency reliability was good with Cronbach's alpha coefficients ranging from 0.74 to 0.86 (lymphoedema 0.80, urological symptoms 0.75, gastrointestinal symptoms 0.74, body image problems 0.86 and sexual/vaginal problems 0.86). Convergent and discriminant validity did not show any scaling errors for the subscales. The QLQ-EN24 module discriminated well between clinically different groups of patients. All items exhibited a high completion rate with less than 2% missing values except for the sexuality items (19%). The validation study supports the reliability, the convergent and divergent validity of the EORTC QLQ-EN24. This newly developed QLQ-EN24 module is a useful instrument for the assessment of the QoL in patients treated for endometrial cancer in clinical trials. Copyright © 2010 Elsevier Ltd. All rights reserved.
Robotic-assisted laparoscopic hysterectomy seems safe in women with early-stage endometrial cancer
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Herling, Suzanne Forsyth; Havemann, Maria Cecilie; Palle, Connie
2015-01-01
INTRODUCTION: Robotic surgery is increasingly used in the management of endometrial cancer; and although it is known that minimally invasive surgery reduces post-operative morbidity, the outcomes of this novel treatment should be monitored carefully. The aim of this study was to examine the incid......INTRODUCTION: Robotic surgery is increasingly used in the management of endometrial cancer; and although it is known that minimally invasive surgery reduces post-operative morbidity, the outcomes of this novel treatment should be monitored carefully. The aim of this study was to examine...... the incidence of complications according to the Clavien-Dindo scale after robotic-assisted laparoscopic hysterectomy (RALH) for early-stage endometrial cancer and atypical complex hyperplasia. The Clavien-Dindo scale grades the severity of complications. METHODS: This was a retrospective, descriptive cohort....... CONCLUSION: The types and frequency of complications observed in this study resemble those reported in similar studies of RALH for malignant gynaecologic conditions. Health-care professionals treating and caring for women with early-stage endometrial cancer should know of the types and frequency of post...
Adjuvant chemotherapy for endometrial cancer after hysterectomy
Johnson, Nick; Bryant, Andrew; Miles, Tracie; Hogberg, Thomas; Cornes, Paul
2014-01-01
Background Endometrial adenocarcinoma (womb cancer) is a malignant growth of the lining (endometrium) of the womb (uterus). It is distinct from sarcomas (tumours of the uterine muscle). Survival depends the risk of microscopic metastases after surgery. Adjuvant (postoperative) chemotherapy improves survival from some other adenocarcinomas, and there is evidence that endometrial cancer is sensitive to cytotoxic therapy. This systematic review examines the effect of chemotherapy on survival after hysterectomy for endometrial cancer. Objectives To assess efficacy of adjuvant (postoperative) chemotherapy for endometrial cancer. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2010, Issue 3), MEDLINE and EMBASE up to August 2010, registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. Selection criteria Randomised controlled trials (RCTs) comparing adjuvant chemotherapy with any other adjuvant treatment or no other treatment. Data collection and analysis We used a random-effects meta-analysis to assess hazard ratios (HR) for overall and progression-free survival and risk ratios (RR) to compare death rates and site of initial relapse. Main results Five RCTs compared no additional treatment with additional chemotherapy after hysterectomy and radiotherapy. Four trials compared platinum based combination chemotherapy directly with radiotherapy. Indiscriminate pooling of survival data from 2197 women shows a significant overall survival advantage from adjuvant chemotherapy (RR (95% CI) = 0.88 (0.79 to 0.99)). Sensitivity analysis focused on trials of modern platinum based chemotherapy regimens and found the relative risk of death to be 0.85 ((0.76 to 0.96); number needed to treat for an additional beneficial outcome (NNT) = 25; absolute risk reduction = 4% (1% to 8%)). The HR for overall survival is 0.74 (0.64 to 0.89), significantly
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Michael P Trimarchi
Full Text Available DNA methylation is a stable epigenetic mark that is frequently altered in tumors. DNA methylation features are attractive biomarkers for disease states given the stability of DNA methylation in living cells and in biologic specimens typically available for analysis. Widespread accumulation of methylation in regulatory elements in some cancers (specifically the CpG island methylator phenotype, CIMP can play an important role in tumorigenesis. High resolution assessment of CIMP for the entire genome, however, remains cost prohibitive and requires quantities of DNA not available for many tissue samples of interest. Genome-wide scans of methylation have been undertaken for large numbers of tumors, and higher resolution analyses for a limited number of cancer specimens. Methods for analyzing such large datasets and integrating findings from different studies continue to evolve. An approach for comparison of findings from a genome-wide assessment of the methylated component of tumor DNA and more widely applied methylation scans was developed.Methylomes for 76 primary endometrial cancer and 12 normal endometrial samples were generated using methylated fragment capture and second generation sequencing, MethylCap-seq. Publically available Infinium HumanMethylation 450 data from The Cancer Genome Atlas (TCGA were compared to MethylCap-seq data.Analysis of methylation in promoter CpG islands (CGIs identified a subset of tumors with a methylator phenotype. We used a two-stage approach to develop a 13-region methylation signature associated with a "hypermethylator state." High level methylation for the 13-region methylation signatures was associated with mismatch repair deficiency, high mutation rate, and low somatic copy number alteration in the TCGA test set. In addition, the signature devised showed good agreement with previously described methylation clusters devised by TCGA.We identified a methylation signature for a "hypermethylator phenotype" in
Yanokura, Megumi; Banno, Kouji; Adachi, Masataka; Aoki, Daisuke; Abe, Kuniya
2017-01-01
Aberrant DNA methylation is widely observed in many cancers. Concurrent DNA methylation of multiple genes occurs in endometrial cancer and is referred to as the CpG island methylator phenotype (CIMP). However, the features and causes of CIMP-positive endometrial cancer are not well understood. To investigate DNA methylation features characteristic to CIMP-positive endometrial cancer, we first classified samples from 25 patients with endometrial cancer based on the methylation status of three ...
Berstein, Lev; Maximov, Sergei; Gershfeld, Eduard; Meshkova, Irina; Gamajunova, Vera; Tsyrlina, Evgenia; Larionov, Alexei; Kovalevskij, Anatolii; Vasilyev, Dmitry
2002-11-15
To investigate the short-term hormonal and clinical effects of the aromatase inhibitor letrozole (Femara) in patients with endometrial cancer. Ten previously untreated, post-menopausal patients (mean age 59 years) with endometrial cancer, predominantly stage I disease, received letrozole 2.5mg per day for 14 days before surgery. Clinical, sonographic, morphologic, cytologic, and hormonal-metabolic parameters (blood estradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), glucose, and cholesterol by radioimmunoassay, enzyme immune assay, or enzyme-colorimetric methods; tumor progesterone receptors by ligand-binding assay; and aromatase activity by 3H-water release assay) were evaluated before and after treatment. Treatment was well-tolerated in all patients. In two patients, pain relief in the lower part of the belly and/or decrease in intensity of uterine discharge was reported. In the three cases, substantial decreases in endometrial M-echo (ultrasound) signal were noted; the mean value of this parameter after treatment was 31.1% lower than before treatment. Blood estradiol concentration decreased by an average of 37.8% after letrozole therapy, and tumor progesterone receptor levels and aromatase activity decreased by 34.4 and 17.5%, respectively. Treatment with letrozole did not influence surgery. These data show that short-term treatment with letrozole in the neoadjuvant setting resulted in some positive clinical changes. Longer-term and larger-scale trials of neoadjuvant letrozole in endometrial cancer are warranted.
Rossi, Peter J; Jani, Ashesh B; Horowitz, Ira R; Johnstone, Peter A S
2008-01-01
To assess the role of radiotherapy (RT) in women with Stage IIIC endometrial cancer. The 17-registry Survival, Epidemiology, and End Results (SEER) database was searched for patients with lymph node-positive non-Stage IV epithelial endometrial cancer diagnosed and treated between 1988 and 1998. Two subgroups were identified: those with organ-confined Stage IIIC endometrial cancer and those with Stage IIIC endometrial cancer with direct extension of the primary tumor. RT was coded as external beam RT (EBRT) or brachytherapy (BT). Observed survival (OS) was reported with a minimum of 5 years of follow-up; the survival curves were compared using the log-rank test. The therapy data revealed 611 women with Stage IIIC endometrial cancer during this period. Of these women, 51% were treated with adjuvant EBRT, 21% with EBRT and BT, and 28% with no additional RT (NAT). Of the 611 patients, 293 had organ-confined Stage IIIC endometrial cancer and 318 patients had Stage IIIC endometrial cancer with direct extension of the primary tumor. The 5-year OS rate for all patients was 40% with NAT, 56% after EBRT, and 64% after EBRT/BT. Adjuvant RT improved survival compared with NAT (p primary tumor was present, the addition of BT to EBRT was even more beneficial.
Estrogen Metabolism and Risk of Postmenopausal Endometrial and Ovarian Cancer: the B ∼ FIT Cohort.
Dallal, Cher M; Lacey, James V; Pfeiffer, Ruth M; Bauer, Douglas C; Falk, Roni T; Buist, Diana S M; Cauley, Jane A; Hue, Trisha F; LaCroix, Andrea Z; Tice, Jeffrey A; Veenstra, Timothy D; Xu, Xia; Brinton, Louise A
2016-02-01
Estrogen metabolites may have different genotoxic and mitogenic properties yet their relationship with endometrial and ovarian cancer risk remains unclear. Within the Breast and Bone Follow-up to the Fracture Intervention Trial (B ∼ FIT, n = 15,595), we conducted a case-cohort study to evaluate 15 pre-diagnostic serum estrogens and estrogen metabolites with risk of incident endometrial and ovarian cancer among postmenopausal women not on hormone therapy. Participants included 66 endometrial and 67 ovarian cancer cases diagnosed during follow-up (∼ 10 years) and subcohorts of 346 and 416 women, respectively, after relevant exclusions. Serum concentrations were measured by liquid chromatography-tandem mass spectrometry. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard regression. Exposures were categorized in tertiles (T) and analyzed individually, as metabolic pathways (C-2, -4, or -16) and as ratios to parent estrogens (estradiol, estrone). Estradiol was significantly associated with increased endometrial cancer risk (BMI-adjusted HRT3vsT1 = 4.09, 95% CI 1.70, 9.85; p trend = 0.003). 2-Hydroxyestrone and 16α-hydroxyestrone were not associated with endometrial risk after estradiol adjustment (2-OHE1:HRT3vsT1 = 1.97, 95% CI 0.78, 4.94; 16-OHE1:HRT3vsT1 = 1.50, 95% CI 0.65, 3.46; p trend = 0.16 and 0.36, respectively). Ratios of 2- and 4-pathway catechol-to-methylated estrogens remained positively associated with endometrial cancer after BMI or estradiol adjustment (2-pathway catechols-to-methylated: HRT3vsT1 = 4.02, 95% CI 1.60, 10.1; 4-pathway catechols-to-methylated: HRT3vsT1 = 4.59, 95% CI 1.64, 12.9; p trend = 0.002 for both). Estrogens and estrogen metabolites were not associated with ovarian cancer risk; however, larger studies are needed to better evaluate these relationships. Estrogen metabolism may be important in endometrial carcinogenesis, particularly with less extensive methylation of 2- or 4
Analysis of PSPHL as a Candidate Gene Influencing the Racial Disparity in Endometrial Cancer
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Allard, Jay E. [Walter Reed Army Medical Center, Washington, DC (United States); Chandramouli, Gadisetti V. R. [Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University College of Human Medicine, Grand Rapids, MI (United States); Stagliano, Katherine [Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center, Savannah, GA (United States); Hood, Brian L. [Women’s Health Integrated Research Center at Inova Health System, Annandale, VA (United States); Litzi, Tracy [Walter Reed Army Medical Center, Washington, DC (United States); Women’s Health Integrated Research Center at Inova Health System, Annandale, VA (United States); Shoji, Yutaka [Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University College of Human Medicine, Grand Rapids, MI (United States); Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center, Savannah, GA (United States); Boyd, Jeff [Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center, Savannah, GA (United States); Fox Chase Cancer Center, Philadelphia, PA (United States); Berchuck, Andrew [Division of Gynecologic Oncology, Duke University, Durham, NC (United States); Conrads, Thomas P. [Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center, Savannah, GA (United States); Maxwell, G. Larry [Walter Reed Army Medical Center, Washington, DC (United States); Women’s Health Integrated Research Center at Inova Health System, Annandale, VA (United States); Risinger, John I., E-mail: john.risinger@hc.msu.edu [Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University College of Human Medicine, Grand Rapids, MI (United States); Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center, Savannah, GA (United States)
2012-07-04
Endometrial cancer is the most commonly diagnosed gynecologic malignancy in the United States. A well recognized disparity by race in both incidence and survival outcome exists for this cancer. Specifically Caucasians are about two times more likely to develop endometrial cancer than are African-Americans. However, African-American women are more likely to die from this disease than are Caucasians. The basis for this disparity remains unknown. Previous studies have identified differences in the types and frequencies of gene mutations among endometrial cancers from Caucasians and African-Americans suggesting that the tumors from these two groups might have differing underlying genetic defects. We performed a gene expression microarray study in an effort to identify differentially expressed transcripts between African-American and Caucasian women’s endometrial cancers. Our gene expression screen identified a list of potential biomarkers that are differentially expressed between these two groups of cancers. Of these we identified a poorly characterized transcript with a region of homology to phospho serine phosphatase (PSPH) and designated phospho serine phosphatase like (PSPHL) as the most differentially over-expressed gene in cancers from African-Americans. We further clarified the nature of expressed transcripts. Northern blot analysis confirmed the message was limited to a transcript of under 1 kB. Sequence analysis of transcripts confirmed two alternate open reading frame (ORF) isoforms due to alternative splicing events. Splice specific primer sets confirmed both isoforms were differentially expressed in tissues from Caucasians and African-Americans. We further examined the expression in other tissues from women to include normal endometrium, normal and malignant ovary. In all cases PSPHL expression was more often present in tissues from African-Americans than Caucasians. Our data confirm the African-American based expression of the PSPHL transcript in
Analysis of PSPHL as a Candidate Gene Influencing the Racial Disparity in Endometrial Cancer
International Nuclear Information System (INIS)
Allard, Jay E.; Chandramouli, Gadisetti V. R.; Stagliano, Katherine; Hood, Brian L.; Litzi, Tracy; Shoji, Yutaka; Boyd, Jeff; Berchuck, Andrew; Conrads, Thomas P.; Maxwell, G. Larry; Risinger, John I.
2012-01-01
Endometrial cancer is the most commonly diagnosed gynecologic malignancy in the United States. A well recognized disparity by race in both incidence and survival outcome exists for this cancer. Specifically Caucasians are about two times more likely to develop endometrial cancer than are African-Americans. However, African-American women are more likely to die from this disease than are Caucasians. The basis for this disparity remains unknown. Previous studies have identified differences in the types and frequencies of gene mutations among endometrial cancers from Caucasians and African-Americans suggesting that the tumors from these two groups might have differing underlying genetic defects. We performed a gene expression microarray study in an effort to identify differentially expressed transcripts between African-American and Caucasian women’s endometrial cancers. Our gene expression screen identified a list of potential biomarkers that are differentially expressed between these two groups of cancers. Of these we identified a poorly characterized transcript with a region of homology to phospho serine phosphatase (PSPH) and designated phospho serine phosphatase like (PSPHL) as the most differentially over-expressed gene in cancers from African-Americans. We further clarified the nature of expressed transcripts. Northern blot analysis confirmed the message was limited to a transcript of under 1 kB. Sequence analysis of transcripts confirmed two alternate open reading frame (ORF) isoforms due to alternative splicing events. Splice specific primer sets confirmed both isoforms were differentially expressed in tissues from Caucasians and African-Americans. We further examined the expression in other tissues from women to include normal endometrium, normal and malignant ovary. In all cases PSPHL expression was more often present in tissues from African-Americans than Caucasians. Our data confirm the African-American based expression of the PSPHL transcript in
Yanokura, Megumi; Banno, Kouji; Adachi, Masataka; Aoki, Daisuke; Abe, Kuniya
2017-06-01
Aberrant DNA methylation is widely observed in many cancers. Concurrent DNA methylation of multiple genes occurs in endometrial cancer and is referred to as the CpG island methylator phenotype (CIMP). However, the features and causes of CIMP-positive endometrial cancer are not well understood. To investigate DNA methylation features characteristic to CIMP-positive endometrial cancer, we first classified samples from 25 patients with endometrial cancer based on the methylation status of three genes, i.e. MLH1, CDH1 (E-cadherin) and APC: CIMP-high (CIMP-H, 2/25, 8.0%), CIMP-low (CIMP-L, 7/25, 28.0%) and CIMP-negative (CIMP(-), 16/25, 64.0%). We then selected two samples each from CIMP-H and CIMP(-) classes, and analyzed DNA methylation status of both normal (peripheral blood cells: PBCs) and cancer tissues by genome-wide, targeted bisulfite sequencing. Genomes of the CIMP-H cancer tissues were significantly hypermethylated compared to those of the CIMP(-). Surprisingly, in normal tissues of the CIMP-H patients, promoter region of the miR-663a locus is hypermethylated relative to CIMP(-) samples. Consistent with this finding, miR-663a expression was lower in the CIMP-H PBCs than in the CIMP(-) PBCs. The same region of the miR663a locus is found to be highly methylated in cancer tissues of both CIMP-H and CIMP(-) cases. This is the first report showing that aberrant DNA methylation of the miR-663a promoter can occur in normal tissue of the cancer patients, suggesting a possible link between this epigenetic abnormality and endometrial cancer. This raises the possibility that the hypermethylation of the miR-663a promoter represents an epimutation associated with the CIMP-H endometrial cancers. Based on these findings, relationship of the aberrant DNA methylation and CIMP-H phenotype is discussed.
Kishimoto, Keiko; Tajima, Shinya; Maeda, Ichiro; Takagi, Masayuki; Ueno, Takahiko; Suzuki, Nao; Nakajima, Yasuo
2016-08-01
Diffusion-weighted imaging (DWI) and the apparent diffusion coefficient (ADC) are widely used for detecting uterine endometrial cancer. The relationships between ADC values and pathological features of endometrial cancer have not yet been established. To investigate whether ADC values of endometrial cancer vary according to histologic tumor cellularity and tumor grade. We retrospectively reviewed 30 pathologically confirmed endometrial cancers. All patients underwent conventional non-enhanced magnetic resonance imaging (MRI) and DWI procedures, and ADC values were calculated. Tumor cellularity was evaluated by counting cancer cells in three high-power ( × 400) fields. The correlation between ADC values and tumor cellularity was assessed using Pearson's correlation coefficient test for statistical analysis. The mean ± standard deviation (SD) ADC value ( ×10(-3) mm(2)/s) of endometrial cancer was 0.85 ± 0.22 (range, 0.55-1.71). The mean ± SD tumor cellularity was 528.36 ± 16.89 (range, 298.0-763.6). ADC values were significantly inversely correlated with tumor cellularity. No significant relationship was observed between ADC values and tumor grade (mean ADC values: G1, 0.88 ± 0.265 × 10(-3) mm(2)/s; G2, 0.80 ± 0.178 × 10(-3) mm(2)/s; G3, 0.81 ± 0.117 × 10(-3) mm(2)/s). There is a significant inverse relationship between ADC values and tumor cellularity in endometrial cancer. No significant differences in average ADC value were observed between G1, G2, and G3 tumors. However, the lower the tumor grade, the wider the SD. © The Foundation Acta Radiologica 2015.
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Karolewski, K.; Kojs, Z.; Jakubowicz, J.; Urbanski, K.; Michalak, A.
2006-01-01
Aim: Analysis of classical prognostic factors in patients with non-advanced endometrial cancer treated with postoperative radiotherapy. Materials/Methods: In the years 1985 - 1999, 705 patients underwent postoperative radiotherapy due to endometrial cancer: 529 patients with FIGO stage I and 176 with FIGO stage II cancer. Mean age was 58 years. In 96% of patients endometrioid adenocarcinoma was found. In 49.9% the cancer had a high, in 27.9% a medium, and in 22.2% a low degree of differentiation. Results: 82% of patients had 5-year disease-free survival. In univariate analysis a significantly higher rate of disease-free survival was observed in: patients younger than 60, with moderately and well differentiated cancers, with stage I endometrioid adenocarcinoma with less than 50% myometrial invasion. In multivariate analysis degree of cancer differentiation was the only independent prognostic factor. Conclusions: In a group of patients with non-advanced endometrial cancer treated with postoperative radiotherapy, degree of cancer differentiation is the primary prognostic factor. (authors)
The role of adhesive molecules in endometrial cancer: part II
Directory of Open Access Journals (Sweden)
Andrzej Malinowski
2010-12-01
Full Text Available The carcinogenesis is a result of both functional and structural disorders in the tissue. It initiates as a mutationin a gene encoding protein that is essential for cellular function. The subsequent cascade of eventsleads to accumulation of mutations and loss of cellular function. The cell loses its tissue-specific morphology,disconnects from other cells and extracellular matrix and migrates – the invasion begins. It is now clear thatadhesive molecules are a key player in this cascade. These proteins of the cell membrane surface are responsiblefor attachment of the cells to each other and to the extracellular matrix. These interactions are crucial forboth structural and functional tissue organization. Lack of this homeostasis destroys the tissue architectureand impairs its function and results in invasion. Abnormal expression of adhesive molecules was reported in allexamined cancers, including endometrial cancer.Endometrial cancer is the most common gynaecological cancer in developed countries. Although in many casesdiagnosed and treated in early stages, and thus with good results, some patients cannot be cured. Completeknowledge of the pathogenesis of the disease will be helpful in identifying the patients with negative prognosticfactors, increased risk of recurrence and, perhaps, to find other therapeutic options. In the paper we are trying tosum up the up-to-date knowledge of the role of adhesive molecules in pathogenesis of endometrial cancer.
Directory of Open Access Journals (Sweden)
Kenji Unno
Full Text Available Most endometrial cancers are detected early and have a good prognosis, while some endometrial cancers are highly invasive, metastasize early, and respond suboptimally to therapy. Currently, appropriate model systems to study the aggressive nature of these tumors are lacking. The objective of this study was to establish a mouse xenograft model of endometrial tumors derived from patients in order to study the biological aggressive characteristics that underlie invasion and metastasis.Endometrial tumor tissue fragments (1.5 mm × 1.5 mm from patients undergoing surgery, were transplanted under the renal capsule of NOD scid gamma mice. After 6-8 weeks, tumors were excised and serially transplanted into additional mice for propagation. Immunohistochemical analysis of the tumors was done for various tumor markers.Four cases of different subtypes of endometrial cancer were grown and propagated in mice. Three of the four tumor cases invaded into the kidneys and to adjacent organs. While all tumors exhibited minimal to no staining for estrogen receptor α, progesterone receptor staining was observed for tumor grafts. In addition, levels and localization of E-cadherin, cytokeratin and vimentin varied depending on subtype. Finally, all tumor xenografts stained positively for urokinase plasminogen activator while 3 tumor xenografts, which showed invasive characteristics, stained positively for urokinase plasminogen activator receptor.Endometrial tumors transplanted under the renal capsule exhibit growth, invasion and local spread. These tumors can be propagated and used to study aggressive endometrial cancer.
Shafiee, Mohamad N; Mongan, Nigel; Seedhouse, Claire; Chapman, Caroline; Deen, Suha; Abu, Jafaru; Atiomo, William
2017-05-01
Women with polycystic ovary syndrome have a three-fold higher risk of endometrial cancer. Insulin resistance and hyperlipidemia may be pertinent factors in the pathogenesis of both conditions. The aim of this study was to investigate endometrial sterol regulatory element binding protein-1 gene expression in polycystic ovary syndrome and endometrial cancer endometrium, and to correlate endometrial sterol regulatory element binding protein-1 gene expression with serum lipid profiles. A cross-sectional study was performed at Nottingham University Hospital, UK. A total of 102 women (polycystic ovary syndrome, endometrial cancer and controls; 34 participants in each group) were recruited. Clinical and biochemical assessments were performed before endometrial biopsies were obtained from all participants. Taqman real-time polymerase chain reaction for endometrial sterol regulatory element binding protein-1 gene and its systemic protein expression were analyzed. The body mass indices of women with polycystic ovary syndrome (29.28 ± 2.91 kg/m 2 ) and controls (28.58 ± 2.62 kg/m 2 ) were not significantly different. Women with endometrial cancer had a higher mean body mass index (32.22 ± 5.70 kg/m 2 ). Sterol regulatory element binding protein-1 gene expression was significantly increased in polycystic ovary syndrome and endometrial cancer endometrium compared with controls (p ovary syndrome, but this was not statistically significant. Similarly, statistically insignificant positive correlations were found between endometrial sterol regulatory element binding protein-1 gene expression and body mass index in endometrial cancer (r = 0.643, p = 0.06) and waist-hip ratio (r = 0.096, p = 0.073). Sterol regulatory element binding protein-1 gene expression was significantly positively correlated with triglyceride in both polycystic ovary syndrome and endometrial cancer (p = 0.028 and p = 0.027, respectively). Quantitative serum sterol regulatory element
SUVmax of 18FDG PET/CT as a predictor of high-risk endometrial cancer patients
DEFF Research Database (Denmark)
Antonsen, Sofie Leisby; Loft, Annika; Fisker, Rune Vincents
2013-01-01
OBJECTIVE: To evaluate SUVmax in the assessment of endometrial cancer preoperatively with particular focus on myometrial invasion (MI), cervical invasion (CI), FIGO stage, risk-stratification and lymph node metastases (LNM). METHODS: A total of 268 women with endometrial cancer or atypical...... endometrial hyperplasia underwent FDG PET/CT imaging before surgical treatment. SUVmax of the primary tumour was compared with histological prognostic factors. RESULTS: SUVmax was significantly higher in patients with high FIGO stages (p...
Brinton, Louise A; Westhoff, Carolyn L; Scoccia, Bert; Lamb, Emmet J; Trabert, Britton; Niwa, Shelley; Moghissi, Kamran S
2013-10-01
Do fertility drugs influence the subsequent risk of endometrial cancer in a manner that is independent of other risk predictors, such as parity? In this follow-up of a large cohort of women evaluated for infertility and for whom information was captured on fertility drugs, indications for usage and other risk factors that might influence cancer risk, we found no evidence for a substantial relationship between fertility drug use and endometrial cancer risk. Although the hormonal etiology of endometrial cancer has been well established, it remains unclear whether the use of fertility drugs has an influence on risk. Results regarding the effects of fertility drugs on endometrial cancer risk have been inconsistent, although several studies have shown some evidence for possible increases in risk. The relationship is of particular interest given that clomiphene, a commonly prescribed drug, is a selective estrogen receptor modulator, with chemical properties similar to tamoxifen, another drug linked to an increase in endometrial cancer risk. In a retrospective cohort of 12 193 women evaluated for infertility between 1965 and 1988 at five US sites, follow-up was pursued through 2010 via both passive as well as active (questionnaire) means. Among the 9832 subjects for whom follow-up was allowed and achieved, 259 346 at-risk person-years (i.e. prior to hysterectomy) were accrued, and 118 invasive endometrial cancers identified. Cox regression determined hazard ratios (HRs) and 95% confidence intervals (CIs) for fertility treatments adjusted for endometrial cancer risk factors and causes of infertility. Although we observed slight increases in endometrial cancer risk associated with clomiphene (HR = 1.39, 95% CI: 0.96-2.01) and the less commonly prescribed gonadotrophins (1.34, 0.76-2.37), there were no convincing relationships of risk with either cycles of use or cumulative exposures for either drug. A statistically significant risk associated with the use of clomiphene
Energy Technology Data Exchange (ETDEWEB)
Inada, Yuki [Department of Radiology, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki City, Osaka 569-8686 (Japan)], E-mail: rad068@poh.osaka-med.ac.jp; Matsuki, Mitsuru; Nakai, Go; Tatsugami, Fuminari; Tanikake, Masato; Narabayashi, Isamu [Department of Radiology, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki City, Osaka 569-8686 (Japan); Yamada, Takashi; Tsuji, Motomu [Department of Pathology, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki City, Osaka 569-8686 (Japan)
2009-04-15
Objective: In this study, the authors discussed the feasibility and value of diffusion-weighted (DW) MR imaging in the detection of uterine endometrial cancer in addition to conventional nonenhanced MR images. Methods and materials: DW images of endometrial cancer in 23 patients were examined by using a 1.5-T MR scanner. This study investigated whether or not DW images offer additional incremental value to conventional nonenhanced MR imaging in comparison with histopathological results. Moreover, the apparent diffusion coefficient (ADC) values were measured in the regions of interest within the endometrial cancer and compared with those of normal endometrium and myometrium in 31 volunteers, leiomyoma in 14 patients and adenomyosis in 10 patients. The Wilcoxon rank sum test was used, with a p < 0.05 considered statistically significant. Results: In 19 of 23 patients, endometrial cancers were detected only on T2-weighted images. In the remaining 4 patients, of whom two had coexisting leiomyoma, no cancer was detected on T2-weighted images. This corresponds to an 83% detection sensitivity for the carcinomas. When DW images and fused DW images/T2-weighted images were used in addition to the T2-weighted images, cancers were identified in 3 of the remaining 4 patients in addition to the 19 patients (overall detection sensitivity of 96%). The mean ADC value of endometrial cancer (n = 22) was (0.97 {+-} 0.19) x 10{sup -3} mm{sup 2}/s, which was significantly lower than those of the normal endometrium, myometrium, leiomyoma and adenomyosis (p < 0.05). Conclusion: DW imaging can be helpful in the detection of uterine endometrial cancer in nonenhanced MR imaging.
Survival after Stage IA Endometrial Cancer; Can follow-up be altered?
DEFF Research Database (Denmark)
Lajer, Henrik; Elnegaard, Sandra; Christensen, René D
2012-01-01
IA (1988 classification) endometrial cancer patients prospectively included between 1986 and 1999. All patients had total abdominal hysterectomy and bilateral salpingo-oophorectomy without adjuvant therapy. Methods. The patient and the disease characteristics were drawn from the DEMCA database....... Of these recurrences, 15 of 23 (65%) were vaginal. Death from recurrence was observed in nine of 23 (39%) patients, and five of these nine had vaginal recurrences. Conclusions. Women with FIGO stage IA endometrial cancer have a very high disease-specific five year survival. Survival was related to histopathology...
CYP19A1 fine-mapping and Mendelian randomization: estradiol is causal for endometrial cancer
Thompson, Deborah J; O'Mara, Tracy A; Glubb, Dylan M; Painter, Jodie N; Cheng, Timothy; Folkerd, Elizabeth; Doody, Deborah; Dennis, Joe; Webb, Penelope M; Gorman, Maggie; Martin, Lynn; Hodgson, Shirley; Michailidou, Kyriaki; Tyrer, Jonathan P; Maranian, Mel J; Hall, Per; Czene, Kamila; Darabi, Hatef; Li, Jingmei; Fasching, Peter A; Hein, Alexander; Beckmann, Matthias W; Ekici, Arif B; Dörk, Thilo; Hillemanns, Peter; Dürst, Matthias; Runnebaum, Ingo; Zhao, Hui; Depreeuw, Jeroen; Schrauwen, Stefanie; Amant, Frederic; Goode, Ellen L; Fridley, Brooke L; Dowdy, Sean C; Winham, Stacey J; Salvesen, Helga B; Trovik, Jone; Njolstad, Tormund S; Werner, Henrica M J; Ashton, Katie; Proietto, Tony; Otton, Geoffrey; Carvajal-Carmona, Luis; Tham, Emma; Liu, Tao; Mints, Miriam; Scott, Rodney J; McEvoy, Mark; Attia, John; Holliday, Elizabeth G; Montgomery, Grant W; Martin, Nicholas G; Nyholt, Dale R; Henders, Anjali K; Hopper, John L; Traficante, Nadia; Ruebner, Matthias; Swerdlow, Anthony J; Burwinkel, Barbara; Brenner, Hermann; Meindl, Alfons; Brauch, Hiltrud; Lindblom, Annika; Lambrechts, Diether; Chang-Claude, Jenny; Couch, Fergus J; Giles, Graham G; Kristensen, Vessela N; Cox, Angela; Bolla, Manjeet K; Wang, Qin; Bojesen, Stig E; Shah, Mitul; Luben, Robert; Khaw, Kay-Tee; Pharoah, Paul D P; Dunning, Alison M; Tomlinson, Ian; Dowsett, Mitch; Easton, Douglas F; Spurdle, Amanda B
2016-01-01
Candidate gene studies have reported CYP19A1 variants to be associated with endometrial cancer and with estradiol (E2) concentrations. We analyzed 2937 single nucleotide polymorphisms (SNPs) in 6608 endometrial cancer cases and 37 925 controls and report the first genome wide-significant association between endometrial cancer and a CYP19A1 SNP (rs727479 in intron 2, P=4.8×10−11). SNP rs727479 was also among those most strongly associated with circulating E2 concentrations in 2767 post-menopausal controls (P=7.4×10−8). The observed endometrial cancer odds ratio per rs727479 A-allele (1.15, CI=1.11–1.21) is compatible with that predicted by the observed effect on E2 concentrations (1.09, CI=1.03–1.21), consistent with the hypothesis that endometrial cancer risk is driven by E2. From 28 candidate-causal SNPs, 12 co-located with three putative gene-regulatory elements and their risk alleles associated with higher CYP19A1 expression in bioinformatical analyses. For both phenotypes, the associations with rs727479 were stronger among women with a higher BMI (Pinteraction=0.034 and 0.066 respectively), suggesting a biologically plausible gene-environment interaction. PMID:26574572
Machida, Hiroko; Hom, Marianne S; Shabalova, Anastasiya; Grubbs, Brendan H; Matsuo, Koji
2017-08-01
The aim of the study was to identify risk factors associated with postoperative urinary tract infections (UTIs) following hysterectomy-based surgical staging in women with endometrial cancer. This is a retrospective study utilizing an institutional database (2008-2016) of stage I-IV endometrial cancer cases that underwent hysterectomy-based surgery. UTIs occurring within a 30-day time period after surgery were examined and correlated to patient clinico-pathological demographics. UTIs were observed in 44 (6.4%, 95% confidence interval 4.6-8.2) out of 687 cases subsequent to the diagnosis of endometrial cancer. UTI cases were significantly associated with obesity, advanced stage, prolonged operative time, hysterectomy type, pelvic lymphadenectomy, non-β-lactam antibiotics, and intraoperative urinary tract injury (all, p Urinary tract infections are common in women following surgical treatment for women with endometrial cancer with risk factors being a prolonged surgical time, radical hysterectomy, and non-guideline perioperative anti-microbial agent use. Consideration of prophylactic anti-microbial agent use in a high-risk group of postoperative urinary tract infection merits further investigation.
Valid and complete data on endometrial cancer in the Danish Gynaecological Cancer Database
DEFF Research Database (Denmark)
Juhl, Caroline S; Hansen, Estrid S; Høgdall, Claus K
2014-01-01
INTRODUCTION: It is a comparative register study designed for data validation of surgery, pathology and recurrence for endometrial cancer in the Danish Gynaecological Cancer Database (DGCD) in the 2005-2009 period. The main outcomes were completeness of the data registered in the DGCD, agreement...... concerning data reported and comparability between the DGCD and a definite reference. MATERIAL AND METHODS: DGCD data on women with endometrial cancer or adenomatous hyperplasia supplemented with patient charts for data on recurrence were retrieved and compared with a definite reference (the pathology report...... and clinical journals). RESULTS: The completeness of data on pathology and surgery reported to the DGCD was 97.3%. The comparability between the DGCG and the definite reference was 94.4%. The agreement for the reported data in the DGCD was 88.3%. For recurrence, the comparability was 94.5% and the agreement...
HNF1B and endometrial cancer risk: results from the PAGE study.
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Veronica Wendy Setiawan
Full Text Available We examined the association between HNF1B variants identified in a recent genome-wide association study and endometrial cancer in two large case-control studies nested in prospective cohorts: the Multiethnic Cohort Study (MEC and the Women's Health Initiative (WHI as part of the Population Architecture using Genomics and Epidemiology (PAGE study. A total of 1,357 incident cases of invasive endometrial cancer and 7,609 controls were included in the analysis (MEC: 426 cases/3,854 controls; WHI: 931 cases/3,755 controls. The majority of women in the WHI were European American, while the MEC included sizable numbers of African Americans, Japanese and Latinos. We estimated the odds ratios (ORs per allele and 95% confidence intervals (CIs of each SNP using unconditional logistic regression adjusting for age, body mass index, and four principal components of ancestry informative markers. The combined ORs were estimated using fixed effect models. Rs4430796 and rs7501939 were associated with endometrial cancer risk in MEC and WHI with no heterogeneity observed across racial/ethnic groups (P ≥ 0.21 or between studies (P ≥ 0.70. The OR(per allele was 0.82 (95% CI: 0.75, 0.89; P = 5.63 × 10(-6 for rs4430796 (G allele and 0.79 (95% CI: 0.73, 0.87; P = 3.77 × 10(-7 for rs7501939 (A allele. The associations with the risk of Type I and Type II tumors were similar (P ≥ 0.19. Adjustment for additional endometrial cancer risk factors such as parity, oral contraceptive use, menopausal hormone use, and smoking status had little effect on the results. In conclusion, HNF1B SNPs are associated with risk of endometrial cancer and that the associated relative risks are similar for Type I and Type II tumors.
DEFF Research Database (Denmark)
Seidelin, Ulla Holten; Ibfelt, Else; Andersen, Ingelise
2016-01-01
characteristics, surgery, body mass index (BMI) and smoking status. Information on highest attained education, cohabitation and comorbidity was obtained from nationwide administrative registries. Logistic regression models were used to determine the association between level of education and cancer stage and Cox......Background: Several studies have documented an association between socioeconomic position and survival from gynaecological cancer, but the mechanisms are unclear. Objective: The aim of this study was to examine the association between level of education and survival after endometrial cancer among...... Danish women; and whether differences in stage at diagnosis and comorbidity contribute to the educational differences in survival. Methods: Women with endometrial cancer diagnosed between 2005 and 2009 were identified in the Danish Gynaecological Cancer Database, with information on clinical...
Adherence to Vaginal Dilation Following High Dose Rate Brachytherapy for Endometrial Cancer
International Nuclear Information System (INIS)
Friedman, Lois C.; Abdallah, Rita; Schluchter, Mark; Panneerselvam, Ashok; Kunos, Charles A.
2011-01-01
Purpose: We report demographic, clinical, and psychosocial factors associated with adherence to vaginal dilation and describe the sexual and marital or nonmarital dyadic functioning of women following high dose rate (HDR) brachytherapy for endometrial cancer. Methods and Materials: We retrospectively evaluated women aged 18 years or older in whom early-stage endometrial (IAgr3-IIB) cancers were treated by HDR intravaginal brachytherapy within the past 3.5 years. Women with or without a sexual partner were eligible. Patients completed questionnaires by mail or by telephone assessing demographic and clinical variables, adherence to vaginal dilation, dyadic satisfaction, sexual functioning, and health beliefs. Results: Seventy-eight of 89 (88%) eligible women with early-stage endometrial cancer treated with HDR brachytherapy completed questionnaires. Only 33% of patients were adherers, based on reporting having used a dilator more than two times per week in the first month following radiation. Nonadherers who reported a perceived change in vaginal dimension following radiation reported that their vaginas were subjectively smaller after brachytherapy (p = 0.013). Adherers reported more worry about their sex lives or lack thereof than nonadherers (p = 0.047). Patients reported considerable sexual dysfunction following completion of HDR brachytherapy. Conclusions: Adherence to recommendations for vaginal dilator use following HDR brachytherapy for endometrial cancer is poor. Interventions designed to educate women about dilator use benefit may increase adherence. Although sexual functioning was compromised, it is likely that this existed before having cancer for many women in our study.
Robotic-assisted laparoscopic hysterectomy seems safe in women with early-stage endometrial cancer
DEFF Research Database (Denmark)
Herling, Suzanne Forsyth; Havemann, Maria Cecilie; Palle, Connie
2015-01-01
INTRODUCTION: Robotic surgery is increasingly used in the management of endometrial cancer; and although it is known that minimally invasive surgery reduces post-operative morbidity, the outcomes of this novel treatment should be monitored carefully. The aim of this study was to examine...... the incidence of complications according to the Clavien-Dindo scale after robotic-assisted laparoscopic hysterectomy (RALH) for early-stage endometrial cancer and atypical complex hyperplasia. The Clavien-Dindo scale grades the severity of complications. METHODS: This was a retrospective, descriptive cohort...... study of 235 women with endometrial cancer or atypical complex hyperplasia who had RALH. Surgeries were stratified into two groups: with or without pelvic lymphadenectomy. RESULTS: A total of 6% developed a grade 3 or higher complication with no significant difference (p = 0.24) between the groups...
Endometrial cancer, types, prognosis, female hormones and antihormones
DEFF Research Database (Denmark)
Ulrich, L S G
2011-01-01
. Prognosis is also dependent on tumor differentiation and stage, and treatment should be adjusted accordingly. In this paper, the different types of endometrial cancer, staging, prognosis, diagnosis, prevention, treatment and their relationship to estrogen and other female hormones are reviewed....
DEFF Research Database (Denmark)
Greimel, Elfriede; Nordin, Andy; Lanceley, Anne
2011-01-01
A validation study was conducted to evaluate the psychometric properties of the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Endometrial Cancer Module (EORTC QLQ-EN24). This module was designed to assess disease and treatment specific aspects of...... of the quality of life (QoL) of patients with endometrial cancer.......A validation study was conducted to evaluate the psychometric properties of the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Endometrial Cancer Module (EORTC QLQ-EN24). This module was designed to assess disease and treatment specific aspects...
Postoperative vaginal radiation in endometrial cancer using a remote afterloading technique
International Nuclear Information System (INIS)
Mandell, L.; Nori, D.; Anderson, L.; Hilaris, B.
1985-01-01
Carcinoma of the endometrium is the most common malignancy of the female genital tract. In early stage endometrial cancer, surgery remains the primary mode of treatment while radiation therapy plays an adjuvant role. Prophylactic vaginal radiation has been shown to reduce significantly the incidence of vaginal recurrences. Between the years 1969-1976, 330 patients with FIGO Stages I and II endometrial cancer were treated according to a standard departmental policy in which 40 Gy of external radiation was given to high risk Stage I and II patients in combination with surgery and intravaginal radiation. With this regimen, the mucosal surface received a total equivalent dose of 40 Gy. These treatments were given on an outpatient basis without the need for any sedation or analgesics. The minimum follow-up was 5 years, with a median follow-up of 8.5 years. The overall pelvic and/or vaginal recurrence rate was 2.7%. The incidence of vaginal complications was 3.7%. The advantages of a remote after loading technique in delivering vaginal vault radiation in endometrial cancer are discussed
Lu, Karen H.; Loose, David S.; Yates, Melinda S.; Nogueras-Gonzalez, Graciela M.; Munsell, Mark F.; Chen, Lee-may; Lynch, Henry; Cornelison, Terri; Boyd-Rogers, Stephanie; Rubin, Mary; Daniels, Molly S.; Conrad, Peggy; Milbourne, Andrea; Gershenson, David M.; Broaddus, Russell R.
2013-01-01
Women with Lynch syndrome have a 40–60% lifetime risk for developing endometrial cancer, a cancer associated with estrogen imbalance. The molecular basis for endometrial-specific tumorigenesis is unclear. Progestins inhibit estrogen-driven proliferation, and epidemiologic studies have demonstrated that progestin-containing oral contraceptives (OCP) reduce the risk of endometrial cancer by 50% in women at general population risk. It is unknown if they are effective in women with Lynch syndrome. Asymptomatic women age 25–50 with Lynch syndrome were randomized to receive the progestin compounds depo-Provera (depoMPA) or OCP for three months. An endometrial biopsy and transvaginal ultrasound were performed before and after treatment. Endometrial proliferation was evaluated as the primary endpoint. Histology and a panel of surrogate endpoint biomarkers were evaluated for each endometrial biopsy as secondary endpoints. A total of 51 women were enrolled, and 46 completed treatment. Two of the 51 women had complex hyperplasia with atypia at the baseline endometrial biopsy and were excluded from the study. Overall, both depoMPA and OCP induced a dramatic decrease in endometrial epithelial proliferation and microscopic changes in the endometrium characteristic of progestin action. Transvaginal ultrasound measurement of endometrial stripe was not a useful measure of endometrial response or baseline hyperplasia. These results demonstrate that women with Lynch syndrome do show an endometrial response to short term exogenous progestins, suggesting that OCP and depoMPA may be reasonable chemopreventive agents in this high-risk patient population. PMID:23639481
Subcutaneous metastasis from endometrial cancer; case report and literature review
Nicolae Bacalbasa; Irina Balescu; Alexandru Filipescu
2018-01-01
Subcutaneous metastases from endometrial cancer are rare situations, only few cases being described so far. The main incriminated mechanisms leading to the apparition of such lesions include hematogenous and lymphatic spread. We present the case of a 66-year-old patient known with previous history of stage IIIA endometroid endometrial carcinoma initially treated by surgery and adjuvant chemotherapy who developed at 18 months follow-up a distant subcutaneous oligometastasis. At this time the p...
Verdoodt, F; Kjaer, S K; Friis, S
2017-06-01
Increasing evidence supports a role for aspirin use in reducing the incidence and mortality of several cancer types. This has spurred a new wave of interest in this widely used drug. In this review, we present and evaluate the epidemiologic evidence of the association between the use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) and the incidence and prognosis of ovarian and endometrial cancer. The evidence of a preventive effect of NSAID use on risk of ovarian or endometrial cancer is based primarily on results from observational studies and, consequently, is only suggestive. Overall, observational studies indicate modest reductions in risk of ovarian and endometrial cancer with aspirin use, whereas the results for non-aspirin NSAID use are equivocal. The strongest inverse associations have been reported for long-term consistent aspirin use, notably among subgroups of users (e.g., those with high body mass index). Few studies have evaluated the influence of NSAID use on the mortality of ovarian or endometrial cancer, and substantial heterogeneity of study characteristics and results preclude any conclusions. Additional studies of aspirin and non-aspirin NSAID use and ovarian or endometrial cancer risk and prognosis are warranted. In the present review, we discuss the importance of comprehensive exposure definitions (i.e., duration, timing, consistency and intensity/dose) and evaluation of potential effect modification according to user characteristics, with the aim of identifying women who may experience the largest benefit of aspirin or non-aspirin NSAID use on risk or prognosis of ovarian and endometrial cancer. Copyright © 2017 Elsevier B.V. All rights reserved.
Zhu, Junyan; Trillsch, Fabian; Mayr, Doris; Kuhn, Christina; Rahmeh, Martina; Hofmann, Simone; Vogel, Marianne; Mahner, Sven; Jeschke, Udo; von Schönfeldt, Viktoria
2018-01-02
Prostaglandin E2 (PGE2) receptor 3 (EP3) regulates tumor cell proliferation, migration, and invasion in numerous cancers. The role of EP3 as a prognostic biomarker in endometrial cancer remains unclear. The primary aim of this study was to analyze the prognostic significance of EP3 expression in endometrial cancer. We analyzed the EP3 expression of 140 endometrial carcinoma patients by immunohistochemistry. RL95-2 endometrial cancer cell line was chosen from four endometrial cancer cell lines (RL95-2, Ishikawa, HEC-1-A, and HEC-1-B) according to EP3 expression level. Treated with PGE2 and EP3 antagonist, RL95-2 cells were investigated by MTT, BrdU, and wound healing assay for functional assessment of EP3. EP3 staining differed significantly according to WHO tumor grading in both whole cohort (p = 0.01) and the subgroup of endometrioid carcinoma (p = 0.01). Patients with high EP3 expression in their respective tumors had impaired progression-free survival as well as overall survival in both cohorts above. EP3 expression in the overall cohort was identified as an independent prognostic marker for progression-free survival (HR 1.014, 95%CI 1.003-1.024, p = 0.01) when adjusted for age, stage, grading, and recurrence. Treatment with EP3 antagonists induced upregulation of estrogen receptor β and decreased activity of Ras and led to attenuated proliferation and migration of RL95-2 cells. EP3 seems to play a crucial role in endometrial cancer progression. In the context of limited systemic treatment options for endometrial cancer, this explorative analysis identifies EP3 as a potential target for diagnostic workup and therapy.
Mok, Zhun Wei; Yong, Eu Leong; Low, Jeffrey Jen Hui; Ng, Joseph Soon Yau
2012-06-01
In Singapore, the standard of care for endometrial cancer staging remains laparotomy. Since the introduction of gynecologic robotic surgery, there have been more data comparing robotic surgery to laparoscopy in the management of endometrial cancer. This study reviewed clinical outcomes in endometrial cancer in a program that moved from laparotomy to robotic surgery. A retrospective review was performed on 124 consecutive endometrial cancer patients. Preoperative data and postoperative outcomes of 34 patients undergoing robotic surgical staging were compared with 90 patients who underwent open endometrial cancer staging during the same period and in the year before the introduction of robotics. There were no significant differences in the mean age, body mass index, rates of diabetes, hypertension, previous surgery, parity, medical conditions, size of specimens, histologic type, or stage of cancer between the robotic and the open surgery groups. The first 20 robotic-assisted cases had a mean (SD) operative time of 196 (60) minutes, and the next 14 cases had a mean time of 124 (64) minutes comparable to that for open surgery. The mean number of lymph nodes retrieved during robot-assisted staging was smaller than open laparotomy in the first 20 cases but not significantly different for the subsequent 14 cases. Robot-assisted surgery was associated with lower intraoperative blood loss (110 [24] vs 250 [83] mL, P robot-assisted endometrial cancer staging after a relatively small number of cases.
18F-FDG PET in the management of endometrial cancer
International Nuclear Information System (INIS)
Chao, Angel; Chang, Ting-Chang; Huang, Huei-Jean; Chou, Hung-Hsueh; Wu, Tzu-I; Ng, Koon-Kwan; Hsueh, Swei; Tsai, Chien-Sheng; Yen, Tzu-Chen; Lai, Chyong-Huey
2006-01-01
Few studies have investigated the clinical impact of whole-body positron emission tomography (PET) with 18 F-fluorodeoxyglucose (FDG) in endometrial cancer. We aimed to assess the value of integrating FDG-PET into the management of endometrial cancer in comparison with conventional imaging alone. All patients with histologically confirmed primary advanced (stage III/IV) or suspicious/documented recurrent endometrial cancer, with poor prognostic features (serum CA-125 >35 U/ml or unfavourable cell types), or surveillance after salvage therapy were eligible. Before FDG-PET scanning, each patient had received magnetic resonance imaging and/or computed tomography (MRI-CT). The receiver operating characteristic curve method with calculation of the area under the curve (AUC) was used to compare the diagnostic efficacy. Clinical impacts were determined on a scan basis. Forty-nine eligible patients were accrued and 60 studies were performed (27 primary staging, 33 post-therapy surveillance or restaging on relapse). The clinical impact was positive in 29 (48.3%) of the 60 scans. Mean standardised uptake values (SUVs) of true-positive lesions were 13.2 (range 5.7-37.4) for central pelvic lesions and 11.1 (range 1.5-37.4) for metastases. The sensitivity of FDG-PET alone (P<0.0001) or FDG-PET plus MRI-CT (P<0.0001) was significantly higher than that of MRI-CT alone in overall lesion detection. FDG-PET plus MRI-CT was significantly superior to MRI-CT alone in overall lesion detection (AUC 0.949 vs 0.872; P=0.004), detection of pelvic nodal/soft tissue metastases (P=0.048) and detection of extrapelvic metastases (P=0.010), while FDG-PET alone was only marginally superior by AUC (P=0.063). Whole-body FDG-PET coupled with MRI-CT facilitated optimal management of endometrial cancer in well-selected cases. (orig.)
International Nuclear Information System (INIS)
Inada, Yuki; Matsuki, Mitsuru; Nakai, Go; Tatsugami, Fuminari; Tanikake, Masato; Narabayashi, Isamu; Yamada, Takashi; Tsuji, Motomu
2009-01-01
Objective: In this study, the authors discussed the feasibility and value of diffusion-weighted (DW) MR imaging in the detection of uterine endometrial cancer in addition to conventional nonenhanced MR images. Methods and materials: DW images of endometrial cancer in 23 patients were examined by using a 1.5-T MR scanner. This study investigated whether or not DW images offer additional incremental value to conventional nonenhanced MR imaging in comparison with histopathological results. Moreover, the apparent diffusion coefficient (ADC) values were measured in the regions of interest within the endometrial cancer and compared with those of normal endometrium and myometrium in 31 volunteers, leiomyoma in 14 patients and adenomyosis in 10 patients. The Wilcoxon rank sum test was used, with a p -3 mm 2 /s, which was significantly lower than those of the normal endometrium, myometrium, leiomyoma and adenomyosis (p < 0.05). Conclusion: DW imaging can be helpful in the detection of uterine endometrial cancer in nonenhanced MR imaging.
Cell-cycle protein expression in a population-based study of ovarian and endometrial cancers
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Ashley S. Felix
2015-02-01
Full Text Available Aberrant expression of cyclin-dependent kinase (CDK inhibitors is implicated in the carcinogenesis of many cancers, including ovarian and endometrial cancers. We examined associations between CDK inhibitor expression, cancer risk factors, tumor characteristics, and survival outcomes among ovarian and endometrial cancer patients enrolled in a population-based case control study. Expression (negative vs. positive of three CDK inhibitors (p16, p21, p27 and ki67 was examined with immunohistochemical staining of tissue microarrays. Logistic regression was used to estimate adjusted odds ratios (ORs and 95% confidence intervals (CIs for associations between biomarkers, risk factors, and tumor characteristics. Survival outcomes were available for ovarian cancer patients and examined using Kaplan-Meier plots and Cox proportional hazards regression. Among ovarian cancer patients (n=175, positive p21 expression was associated with endometrioid tumors (OR=12.22, 95% CI=1.45-102.78 and higher overall survival (log-rank p=0.002. In Cox models adjusted for stage, grade, and histology, the association between p21 expression and overall survival was borderline significant (hazard ratio=0.65, 95% CI=0.42-1.05. Among endometrial cancer patients (n=289, positive p21 expression was inversely associated with age (OR ≥ 65 years of age=0.25, 95% CI=0.07-0.84 and current smoking status (OR: 0.33, 95% CI 0.15, 0.72 compared to negative expression. Our study showed heterogeneity in expression of cell-cycle proteins associated with risk factors and tumor characteristics of gynecologic cancers. Future studies to assess these markers of etiological classification and behavior may be warranted.
Xu, Wang Hong; Zheng, Wei; Xiang, Yong Bing; Ruan, Zhi Xian; Cheng, Jia Rong; Dai, Qi; Gao, Yu Tang; Shu, Xiao Ou
2004-01-01
Objective To evaluate the association of intake of soya food, a rich source of phytoestrogens, with the risk of endometrial cancer. Design Population based case-control study, with detailed information on usual soya food intake over the past five years collected by face to face interview using a food frequency questionnaire. Setting Urban Shanghai, China. Participants 832 incident cases of endometrial cancer in women aged of 30 to 69 years diagnosed during 1997-2001 and identified from the Shanghai Cancer Registry; 846 control women frequency matched to cases on age and randomly selected from the Shanghai Residential Registry. Main outcome measures Odds ratios for risk of endometrial cancer in women with different intakes of soya foods. Results Regular consumption of soya foods, measured as amount of either soya protein or soya isoflavones, was inversely associated with the risk of endometrial cancer. Compared with women with the lowest quarter of intake, the adjusted odds ratio of endometrial cancer was reduced from 0.93 to 0.85 and 0.67 with increasing quarter of soya protein intake (P for trend 0.01). A similar inverse association was observed for soya isoflavones and soya fibre intake. The inverse association seemed to be more pronounced among women with high body mass index and waist:hip ratio. Conclusion Regular intake of soya foods is associated with a reduced risk of endometrial cancer. PMID:15136343
Hackenberg, R; Loos, S; Nia, A H; Kunzmann, R; Schulz, K D
1998-01-01
MFE-280 endometrial cancer cells express PP14 (placental protein 14) in vitro. PP14 is normally found in the secretory endometrium and in placental tissue. MFE-280 cells, which are tumorigenic in nude mice, were derived from a recurrent, poorly differentiated endometrial carcinoma. The cells were initially grown in suspension culture and later transferred to monolayer cultures. Karyotyping revealed near-diploidy with a complex heterogeneous aberration pattern. MFE-280 cells were positive for the cytokeratins 7, 8, 18 and 19 as well as for vimentin. The expression of PP14 in MFE-280 cells was demonstrated by immunochemistry and reverse transcriptase--polymerase chain reaction. PP14-mRNA was also detected in one out of five endometrial cancer specimen. In tumor tissue the expression of PP14 was not dependent on progestins.
Vabrasio is a reliable test to rule out endometrial cancer
DEFF Research Database (Denmark)
Andersen, Anita; Lauszus, Finn Friis
2015-01-01
Introduction: Endometrial cancer is the most common gynaecological cancer in Denmark, and its incidence peaks in the postmenopausal years. The aim of the present study was to evaluate the effectiveness of vacuum aspirator (vabrasio) for the detection of endometrial cancer in terms of sensitivity......, specificity and predictive value. Methods: A cohort counting 503 women who had vabrasio was evaluated retrospectively. The women included were consecutive patients who had received vabrasio at the Department of Gynaecology and Obstetrics at Herning Hospital, Denmark, during a two-year period. They were iden......tified by searching the hospital database for the International Classification of Diseases, tenth version (ICD-10) code for vabrasio. Results: The indications for vabrasio were postmenopausal bleeding (45%), meno/metrorrhagia (43%) and thickened endometrium/polyp (6%). The first evaluation by vabrasio was normal...
Acute toxicity of postoperative IMRT and chemotherapy for endometrial cancer
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Tierney, R.M.; Powell, M.A.; Mutch, D.G.; Gibb, R.K.; Rader, J.S.; Grigsby, P.W.
2007-01-01
The aim of this study was to determine the acute toxicity of postoperative intensity-modulated radiotherapy (IMRT) with and without chemotherapy in patients with endometrial cancer. A total of 19 patients with stages IB-IVB endometrial cancer who underwent surgery and postoperative IMRT were reviewed. The treatment planning goal was to cover the tissue at risk and minimize the dose to the bladder, bowel, and bone marrow. Median dose was 50.4 Gy (range 49.6-51.2 Gy). Altogether, 14 patients underwent chemotherapy; most were given carboplatin and paclitaxel. Toxicity was scored according to the Common Terminology Criteria for Adverse Events version 3.0 (CTCAE). The prescribed radiation treatment was completed in all patients. The prescribed cycles of chemotherapy were completed in all 14 patients, except one who received five of six cycles limited by prolonged thrombocytopenia. Chemotherapy was delayed in two patients (14%). Three patients required growth factor support during chemotherapy, and one patient required a blood transfusion. Acute grades 3-4 hematological toxicity occurred in 9 of the 14 patients (64%) who underwent chemotherapy. None experienced acute grade 3 or 4 genitourinary or gastrointestinal toxicity. Adjuvant IMRT and chemotherapy following surgery in patients with endometrial cancer is well tolerated and did not lead to treatment modification in most patients. (author)
DEFF Research Database (Denmark)
Eriksson, LS; Lindqvist, PG; Flöter Rådestad, A
2014-01-01
OBJECTIVES: To assess interobserver reproducibility among ultrasound experts and gynaecologists in the prediction of deep myometrial- and cervical stroma invasion by transvaginal ultrasound in women with endometrial cancer. METHODS: Video-clips of the corpus- and cervix uteri of 53 women...... with endometrial cancer, examined preoperatively by the same ultrasound expert, were integrated in a digitalized survey. Nine ultrasound experts and 9 gynaecologists evaluated presence or absence of deep myometrial- and cervical stroma invasion. Histopathology from hysterectomy specimen was used as gold standard.......001). CONCLUSION: Preoperative ultrasound assessment of deep myometrial- and cervical stroma invasion in endometrial cancer is best performed by ultrasound experts, as they show a higher degree of agreement to histopathology and higher interobserver reproducibility in the assessment of cervical stromal invasion....
Directory of Open Access Journals (Sweden)
Jay eAllard
2012-07-01
Full Text Available Endometrial cancer is the most commonly diagnosed gynecologic malignancy in the United States and is characterized by a well recognized racial disparity in both incidence and survival. Specifically Caucasians are about two times more likely to develop endometrial cancer than are African Americans. However, African American women are more likely to die from this disease than are Caucasians. The basis for this disparity remains unknown. Previous studies have identified differences in the types and frequencies of gene mutations among endometrial cancers from Caucasians and African Americans suggesting. We performed a gene expression microarray study in an effort to further examine differences between African American and Caucasian women’s endometrial cancers. This expression screen identified a list of potential biomarkers differentially expressed between these two groups of cancers. Of these we identified a poorly characterized transcript with a region of homology to phospho serine phospatase (PSPH and designated phospho serine phospatase like (PSPHL as the most differentially over-expressed gene in cancers from African Americans. We clarified the nature of expressed transcripts. Northern blot analysis confirmed PSPHL messages under 1 KB. Sequence analysis of transcripts confirmed two alternate open reading frame (ORF isoforms due to alternative splicing events. Splice specific primer sets confirmed both isoforms were differentially expressed in tissues from Caucasians and African Americans. We further examined the expression in other tissues from women to include normal endometrium, normal and malignant ovary. In all cases PSPHL expression was more often present in tissues from African-Americans than Caucasians. Our data confirm the African-American based expression of the PSPHL transcript several tissue types. PSPHL represents a candidate gene that might influence the observed racial disparity in endometrial and other cancers.
Directory of Open Access Journals (Sweden)
Wan-Ju Wu
2013-06-01
Conclusion: In patients with endometrial cancer, a preoperative MRI contributes to accurate staging, allowing planning for the scale of surgery and preoperative counseling. In our study, the pretreatment identification of myometrium invasion provided the opportunity for small-scale surgery in the premenopausal women with early endometrial cancer. However, for the postmenopausal patients, the standard surgical procedure is indicated even if the degree of myometrium invasion is low.
Chao, Angel; Lai, Chyong-Huey; Lee, Yun-Shien; Ueng, Shir-Hwa; Lin, Chiao-Yun; Wang, Tzu-Hao
2015-01-15
Endometrial cancer that occurs concurrently with peritoneal malignant mesothelioma (PMM) is difficult to diagnose preoperatively. A postmenopausal woman had endometrial cancer extending to the cervix, vagina and pelvic lymph nodes, and PMM in bilateral ovaries, cul-de-sac, and multiple peritoneal sites. Adjuvant therapies included chemotherapy and radiotherapy. Targeted, massively parallel DNA sequencing and molecular inversion probe microarray analysis revealed a germline TP53 mutation compatible with Li-Fraumeni-like syndrome, somatic mutations of PIK3CA in the endometrial cancer, and a somatic mutation of GNA11 and JAK3 in the PMM. Large-scale genomic amplifications and some deletions were found in the endometrial cancer. The patient has been stable for 24 months after therapy. One of her four children was also found to carry the germline TP53 mutation. Molecular characterization of the coexistent tumors not only helps us make the definite diagnosis, but also provides information to select targeted therapies if needed in the future. Identification of germline TP53 mutation further urged us to monitor future development of malignancies in this patient and encourage cancer screening in her family.
The risk of extra-colonic, extra-endometrial cancer in the Lynch syndrome
DEFF Research Database (Denmark)
Watson, Patrice; Vasen, Hans F A; Mecklin, Jukka-Pekka
2008-01-01
Persons with the Lynch syndrome (LS) are at high risk for cancer, including cancers of the small bowel, stomach, upper urologic tract (renal pelvis and ureter), ovary, biliary tract and brain tumors, in addition to the more commonly observed colorectal and endometrial cancers. Cancer prevention...
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Che, Qi; Liu, Bin-Ya; Wang, Fang-Yuan; He, Yin-Yan; Lu, Wen; Liao, Yun [Department of Obstetrics and Gynecology, Shanghai First People’s Hospital Affiliated to Shanghai Jiao Tong University, Shanghai (China); Gu, Wei, E-mail: krisgu70@163.com [Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai (China); Wan, Xiao-Ping, E-mail: wanxp@sjtu.edu.cn [Department of Obstetrics and Gynecology, Shanghai First Maternity and Infant Hospital Affiliated to Tong Ji University, Shanghai (China)
2014-03-28
Highlights: • IL-6 could promote endometrial cancer cells proliferation. • IL-6 promotes its own production through an autocrine feedback loop. • ERK and NF-κB pathway inhibitors inhibit IL-6 production and tumor growth. • IL-6 secretion relies on the activation of ERK–NF-κB pathway axis. • An orthotopic nude endometrial carcinoma model confirms the effect of IL-6. - Abstract: Interleukin (IL)-6 as an inflammation factor, has been proved to promote cancer proliferation in several human cancers. However, its role in endometrial cancer has not been studied clearly. Previously, we demonstrated that IL-6 promoted endometrial cancer progression through local estrogen biosynthesis. In this study, we proved that IL-6 could directly stimulate endometrial cancer cells proliferation and an autocrine feedback loop increased its production even after the withdrawal of IL-6 from the medium. Next, we analyzed the mechanism underlying IL-6 production in the feedback loop and found that its production and IL-6-stimulated cell proliferation were effectively blocked by pharmacologic inhibitors of nuclear factor-kappa B (NF-κB) and extra-cellular signal-regulated kinase (ERK). Importantly, activation of ERK was upstream of the NF-κB pathways, revealing the hierarchy of this event. Finally, we used an orthotopic nude endometrial carcinoma model to confirm the effects of IL-6 on the tumor progression. Taken together, these data indicate that IL-6 promotes endometrial carcinoma growth through an expanded autocrine regulatory loop and implicate the ERK–NF-κB pathway as a critical mediator of IL-6 production, implying IL-6 to be an important therapeutic target in endometrial carcinoma.
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Shinsuke Hanawa
Full Text Available Metformin, an antidiabetic drug, inhibits the endometrial cancer cell growth in vivo by improving the insulin resistance; however, its mechanism of action is not completely understood. Protein phosphatase 2A (PP2A is a serine/threonine phosphatase associated with insulin resistance and type 2 diabetes, and its inhibition restores the insulin resistance. This study investigated the antitumor effect of metformin on endometrial cancer with a focus on PP2A.Metformin (1,500-2,250 mg/day was preoperatively administered to patients with endometrial cancer for 4 to 6 weeks. Expression of the PP2A regulatory subunits, 4 (PPP2R4 and B (PP2A-B, was evaluated using real-time polymerase chain reaction (RT-PCR and immunohistochemistry (IHC using paired specimens obtained before and after metformin treatment. The effect of PPP2R4 inhibition with small interfering RNA was evaluated in the endometrial cancer cell lines HEC265 and HEC1B. P values of < .05 were considered statistically significant.Preoperative metformin treatment significantly reduced the expression of PP2A-B, as determined using IHC, and the mRNA expression of PPP2R4, as determined using RT-PCR, in the patients with endometrial cancer. However, metformin could not directly alter the PPP2R4 mRNA levels in the endometrial cancer cell lines in vitro. PPP2R4 knockdown reduced the proliferation and induced the apoptosis by activating caspases 3/7 in HEC265 and HEC1B cells.Downregulation of the PP2A-B subunit, including PPP2R4, is an important indirect target of metformin. Inhibition of PP2A may be an option for the treatment of endometrial cancer patients with insulin resistance.This trial is registered with UMIN-CTR (number UMIN000004852.
Wilczynski, Milosz; Danielska, Justyna; Domanska-Senderowska, Daria; Dzieniecka, Monika; Szymanska, Bozena; Malinowski, Andrzej
2018-05-01
MicroRNAs (miRNAs) are regulators of gene expression, which play an important role in many critical cellular processes including apoptosis, proliferation and cell differentiation. Aberrant miRNA expression has been reported in a variety of human malignancies. Therefore, miRNAs may be potentially used as cancer biomarkers. miRNA-200c, which is a member of the miRNA-200 family, might play an essential role in tumor progression. The purpose of this study was to evaluate the prognostic and clinical significance of miRNA-200c in women with endometrioid endometrial cancer. Total RNA extraction from 90 archival formalin-fixed paraffin-embedded tissue samples of endometri-oid endometrial cancer and 10 normal endometrium samples was performed. After cDNA synthesis, real-time polymerase chain reaction was conducted and relative expression of miRNA-200c was assessed. Then, miRNA-200c expression levels were evaluated with regard to clinicopathological characteristics. The expression levels of miRNA-200c were significantly increased in endometrioid endometrial cancer samples. Expression of miRNA-200c maintained at significantly higher levels in the early stage endometrioid endometrial cancer compared with more advanced stages. In the Kaplan-Meier analysis, lower levels of miRNA-200c expression were associated with inferior survival. Expression levels of miRNA-200c might be associated with clinicopathological factors and survival in endometrioid endometrial cancer. © 2018 Nordic Federation of Societies of Obstetrics and Gynecology.
International Nuclear Information System (INIS)
Kim, Hyun Jeong; Choi, Jiyoun; Jeong, Yong Hyu; Jo, Kwan Hyeong; Lee, Jaehoon; Cho, Arthur; Yun, Mijin; Lee, Jong Doo; Kim, Young Tae; Kang, Won Jun
2013-01-01
We evaluated the potential prognostic value of 18 F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in patients with stage IIIC/IV endometrial cancer. Patients with stage IIIC/IV endometrial cancer who had undergone FDG PET/CT workup for staging were enrolled. Maximum standardized uptake values (SUV max ) measured from regions of interest (ROIs) of the primary tumor (SUVt) and lymph nodes (SUVn) were correlated with overall survival (OS). The SUVn was defined as the highest SUV max of the metastatic lymph nodes. Survival probability was assessed using the Kaplan-Meier method. A total of 42 patients with a median age of 55.5 years (range 32-76 years) were included. Twenty-nine percent (n =12) of patients were premenopausal and 71 % (n =30) were postmenopausal. The average SUVt was 12.9 (range 1.8-36.5), and the average SUVn was 7.3 (range 2.0-22.5). Median follow-up time was 25.9 months (range 1.84 months). Using a SUVt of 9.5 as a cutoff value, two groups with different rates were determined (P=0.026). In addition, patients with a low SUVn had significantly better OS than those with a high SUVn (P=0.003). Patients in the International Federation of Obstetrics and Gynecology (FIGO) stage IV group with SUVt≥9.5 or SUVn≥7.3 showed a significantly longer OS than the other groups. FDG uptake of primary endometrial cancer and lymph nodes might be a prognostic factor in advanced endometrial cancer. More aggressive therapy could be considered in patients with stage IV endometrial cancer and high SUVt and/or high SUVn
Oncogenic events associated with endometrial and ovarian cancers are rare in endometriosis
DEFF Research Database (Denmark)
Vestergaard, Anna Lindeløv; Thorup, Katrine; Knudsen, Ulla Breth
2011-01-01
Endometriosis displays some features that resemble malignant processes, including invasive growth, resistance to apoptosis, and distant implantation. The objective of this study was to investigate whether gene alterations that are frequent in endometrial and/or ovarian cancers contribute to the p......Endometriosis displays some features that resemble malignant processes, including invasive growth, resistance to apoptosis, and distant implantation. The objective of this study was to investigate whether gene alterations that are frequent in endometrial and/or ovarian cancers contribute...... to the pathogenesis of endometriosis. Biopsies were obtained from ectopic endometriosis lesions from 23 patients with revised American Fertility Score (rAFS) stage 1 (N=1), 2 (N=10), 3 (N=11), or 4 (N=1) endometriosis. Six genes (APC, CDKN2A, PYCARD, RARB, RASSF1, and ESR1) were analyzed for promoter hypermethylation...... in a single lesion. No gene alterations were found in the remaining samples. Our data suggest that genetic and epigenetic events contributing to endometrial and ovarian cancers are rare in endometriosis. However, other proto-oncogenes and tumor suppressor genes should be tested for alterations in order...
Endometrial adenocarcinoma in a 13-year-old girl.
Kim, Sung Mee; Shin, So Jin; Bae, Jin Gon; Kwon, Kun Young; Rhee, Jeong Ho
2016-03-01
Endometrial cancer is the third most common gynecologic cancer in the Korea and occurs mainly in menopausal women. Although it can develop in young premenopausal women cancer as well, an attack in the adolescent girl is very rare. A 13-year-old girl visited gynecology department with the complaint of abnormal uterine bleeding. An endometrial biopsy revealed FIGO (International Federation of Gynecology and Obstetrics) grade II endometrial adenocarcinoma. In the treatment of endometrial cancer, conservative management should be considered if the patient is nulliparous or wants the fertility preservation. Therefore, we decided to perform a hormonal therapy and a follow-up endometrial biopsy after progestin administration for eight months revealed no residual tumor. We report a case of endometrial cancer occurred in a 13-year-old girl with a brief review of the literature.
Molecular alterations in endometrial cancer : implications for clinical management
Stelloo, E.
2017-01-01
Over the last decades, advances have been made in the treatment of endometrial cancer. The clinicopathological risk stratification for postoperative therapy has considerably reduced overtreatment by refining indications and introducing treatment with fewer side effects. Despite refinement in the use
Sentinel lymph node biopsy in endometrial cancer-Feasibility, safety and lymphatic complications.
Geppert, Barbara; Lönnerfors, Céline; Bollino, Michele; Persson, Jan
2018-03-01
To compare the rate of lymphatic complications in women with endometrial cancer undergoing sentinel lymph node biopsy versus a full pelvic and infrarenal paraaortic lymphadenectomy, and to examine the overall feasibility and safety of the former. A prospective study of 188 patients with endometrial cancer planned for robotic surgery. Indocyanine green was used to identify the sentinel lymph nodes. In low-risk patients the lymphadenectomy was restricted to removal of sentinel lymph nodes whereas in high-risk patients also a full lymphadenectomy was performed. The impact of the extent of the lymphadenectomy on the rate of complications was evaluated. The bilateral detection rate of sentinel lymph nodes was 96% after cervical tracer injection. No intraoperative complication was associated with the sentinel lymph node biopsy per se. Compared with hysterectomy alone, the additional average operative time for removal of sentinel lymph nodes was 33min whereas 91min were saved compared with a full pelvic and paraaortic lymphadenectomy. Sentinel lymph node biopsy alone resulted in a lower incidence of leg lymphedema than infrarenal paraaortic and pelvic lymphadenectomy (1.3% vs 18.1%, p=0.0003). The high feasibility, the absence of intraoperative complications and the low risk of lymphatic complications supports implementing detection of sentinel lymph nodes in low-risk endometrial cancer patients. Given that available preliminary data on sensitivity and false negative rates in high-risk patients are confirmed in further studies, we also believe that the reduction in lymphatic complications and operative time strongly motivates the sentinel lymph node concept in high-risk endometrial cancer. Copyright © 2017. Published by Elsevier Inc.
Costs of Robotic-Assisted Versus Traditional Laparoscopy in Endometrial Cancer.
Vuorinen, Riikka-Liisa K; Mäenpää, Minna M; Nieminen, Kari; Tomás, Eija I; Luukkaala, Tiina H; Auvinen, Anssi; Mäenpää, Johanna U
2017-10-01
The purpose of this study was to compare the costs of traditional laparoscopy and robotic-assisted laparoscopy in the treatment of endometrial cancer. A total of 101 patients with endometrial cancer were randomized to the study and operated on starting from 2010 until 2013, at the Department of Obstetrics and Gynecology of Tampere University Hospital, Tampere, Finland. Costs were calculated based on internal accounting, hospital database, and purchase prices and were compared using intention-to-treat analysis. Main outcome measures were item costs and total costs related to the operation, including a 6-month postoperative follow-up. The total costs including late complications were 2160 &OV0556; higher in the robotic group (median for traditional 5823 &OV0556;, vs robot median 7983 &OV0556;, P costs for instruments and equipment as well as to more expensive operating room and postanesthesia care unit time. Traditional laparoscopy involved higher costs for operation personnel, general costs, medication used in the operation, and surgeon, although these costs were not substantial. There was no significant difference in in-patient stay, laboratory, radiology, blood products, or costs related to complications. According to this study, robotic-assisted laparoscopy is 37% more expensive than traditional laparoscopy in the treatment of endometrial cancer. The cost difference is mainly explained by amortization of the robot and its instrumentation.
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Jeffery M. Vahrenkamp
2018-03-01
Full Text Available Summary: Steroid hormone receptors are simultaneously active in many tissues and are capable of altering each other’s function. Estrogen receptor α (ER and glucocorticoid receptor (GR are expressed in the uterus, and their ligands have opposing effects on uterine growth. In endometrial tumors with high ER expression, we surprisingly found that expression of GR is associated with poor prognosis. Dexamethasone reduced normal uterine growth in vivo; however, this growth inhibition was abolished in estrogen-induced endometrial hyperplasia. We observed low genomic-binding site overlap when ER and GR are induced with their respective ligands; however, upon simultaneous induction they co-occupy more sites. GR binding is altered significantly by estradiol with GR recruited to ER-bound loci that become more accessible upon estradiol induction. Gene expression responses to co-treatment were more similar to estradiol but with additional regulated genes. Our results suggest phenotypic and molecular interplay between ER and GR in endometrial cancer. : Estrogen receptor α (ER and glucocorticoid receptor (GR are expressed in the uterus and have differential effects on growth. Vahrenkamp et al. find that expression of both receptors is associated with poor outcome in endometrial cancer and that simultaneous induction of ER and GR leads to molecular interplay between the receptors. Keywords: estrogen receptor, glucocorticoid receptor, endometrial cancer
Is postmenopausal endometrial fluid collection alone a risk factor for endometrial cancer?
Yegin Akcay, Gulin Feykan; Tas, Emre Erdem; Yavuz, Ayse Filiz
2018-01-01
To determine the usefulness of single-layer, ultrasonographic measurement of endometrial fluid collection (EFC) volume to predict endometrial pathology in asymptomatic postmenopausal patients. One hundred fifty asymptomatic postmenopausal women were analysed retrospectively from January 2012 to December 2016. After patients with endometrial hyperplasia/neoplasia were included in Group-I, and those with insufficient tissue, endometrial atrophy, or endometritis were included in Group-II; Groups one and two were compared with respect to primary (correlations between endometrial thickness and EFC volume) and secondary (correlations between demographic characteristics and EFC volume) outcomes. There was no correlation between EFC volume and single-layer endometrial thickness ( P = 0.36). Likewise, demographic characteristics were not related to EFC ( P > 0.05). However, both EFC volume and single-layer endometrial thickness were thicker in Group-I compared to Group-II (4.8 ± 1.9 mm vs . 3.7 ± 2.5 mm; and 5.7 ± 9.4 mm vs . 2.7 ± 2.5 mm, respectively) ( P values were < 0.05). Although a cutoff value for endometrial thickness and EFC volume could not be recommended based on our study findings, it should be noted that 2% is a clinically significant rate of malignancy. Thus, postmenopausal patients with EFC should be evaluated for endometrial sampling.
Robotic-assisted laparoscopic hysterectomy for women with endometrial cancer
DEFF Research Database (Denmark)
Herling, Suzanne Forsyth; Møller, Ann M; Palle, Connie
2017-01-01
-anaesthesia care unit was shorter for patients undergoing RALH. CONCLUSIONS: RALH appears advantageous for women treated for endometrial cancer in terms of post-operative complications. We recommend the use of the Clavien-Dindo classification of surgical outcomes for quality assessment. FUNDING: departmental only...
Buchanan, Daniel D; Rosty, Christophe; Clendenning, Mark; Spurdle, Amanda B; Win, Aung Ko
2014-01-01
Carriers of a germline mutation in one of the DNA mismatch repair (MMR) genes have a high risk of developing numerous different cancers, predominantly colorectal cancer and endometrial cancer (known as Lynch syndrome). MMR gene mutation carriers develop tumors with MMR deficiency identified by tumor microsatellite instability or immunohistochemical loss of MMR protein expression. Tumor MMR deficiency is used to identify individuals most likely to carry an MMR gene mutation. However, MMR deficiency can also result from somatic inactivation, most commonly methylation of the MLH1 gene promoter. As tumor MMR testing of all incident colorectal and endometrial cancers (universal screening) is becoming increasingly adopted, a growing clinical problem is emerging for individuals who have tumors that show MMR deficiency who are subsequently found not to carry an MMR gene mutation after genetic testing using the current diagnostic approaches (Sanger sequencing and multiplex ligation-dependent probe amplification) and who also show no evidence of MLH1 methylation. The inability to determine the underlying cause of tumor MMR deficiency in these "Lynch-like" or "suspected Lynch syndrome" cases has significant implications on the clinical management of these individuals and their relatives. When the data from published studies are combined, 59% (95% confidence interval [CI]: 55% to 64%) of colorectal cancers and 52% (95% CI: 41% to 62%) of endometrial cancers with MMR deficiency were identified as suspected Lynch syndrome. Recent studies estimated that colorectal cancer risk for relatives of suspected Lynch syndrome cases is lower than for relatives of those with MMR gene mutations, but higher than for relatives of those with tumor MMR deficiency resulting from methylation of the MLH1 gene promoter. The cause of tumor MMR deficiency in suspected Lynch syndrome cases is likely due to either unidentified germline MMR gene mutations, somatic cell mosaicism, or biallelic somatic
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Kim, Hyun Jeong; Choi, Jiyoun; Jeong, Yong Hyu; Jo, Kwan Hyeong; Lee, Jaehoon; Cho, Arthur; Yun, Mijin; Lee, Jong Doo; Kim, Young Tae; Kang, Won Jun [Yonsei Univ. College of Medicine, Seoul (Korea, Republic of)
2013-12-15
We evaluated the potential prognostic value of {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in patients with stage IIIC/IV endometrial cancer. Patients with stage IIIC/IV endometrial cancer who had undergone FDG PET/CT workup for staging were enrolled. Maximum standardized uptake values (SUV{sub max}) measured from regions of interest (ROIs) of the primary tumor (SUVt) and lymph nodes (SUVn) were correlated with overall survival (OS). The SUVn was defined as the highest SUV{sub max} of the metastatic lymph nodes. Survival probability was assessed using the Kaplan-Meier method. A total of 42 patients with a median age of 55.5 years (range 32-76 years) were included. Twenty-nine percent (n =12) of patients were premenopausal and 71 % (n =30) were postmenopausal. The average SUVt was 12.9 (range 1.8-36.5), and the average SUVn was 7.3 (range 2.0-22.5). Median follow-up time was 25.9 months (range 1.84 months). Using a SUVt of 9.5 as a cutoff value, two groups with different rates were determined (P=0.026). In addition, patients with a low SUVn had significantly better OS than those with a high SUVn (P=0.003). Patients in the International Federation of Obstetrics and Gynecology (FIGO) stage IV group with SUVt≥9.5 or SUVn≥7.3 showed a significantly longer OS than the other groups. FDG uptake of primary endometrial cancer and lymph nodes might be a prognostic factor in advanced endometrial cancer. More aggressive therapy could be considered in patients with stage IV endometrial cancer and high SUVt and/or high SUVn.
Directory of Open Access Journals (Sweden)
Chi-Chang Chang
2016-08-01
Full Text Available Type II endometrial carcinoma typically exhibits aggressive metastasis and results in a poor prognosis. Siegesbeckia orientalis Linne is a traditional Chinese medicinal herb with several medicinal benefits, including the cytotoxicity against various cancers. This study investigates the inhibitory effects of S. orientalis ethanol extract (SOE on the migration and invasion of endometrial cancer cells, which were stimulated by transforming growth factor β (TGFβ. The inhibitory effects were evaluated by determining wound healing and performing the Boyden chamber assay. This study reveals that SOE can inhibit TGFβ1-induced cell wound healing, cell migration, and cell invasion in a dose-dependent manner in RL95-2 and HEC-1A endometrial cancer cells. SOE also reversed the TGFβ1-induced epithelial-mesenchymal transition, including the loss of the cell-cell junction and the lamellipodia-like structures. Western blot analysis revealed that SOE inhibited the phosphorylation of ERK1/2, JNK1/2, and Akt, as well as the expression of MMP-9, MMP-2, and u-PA in RL95-2 cells dose-dependently. The results of this investigation suggest that SOE is a potential anti-metastatic agent against human endometrial tumors.
A new afterloading applicator for primary brachytherapy of endometrial cancer
International Nuclear Information System (INIS)
Bauer, M.; Schulz-Wendtland, R.
1993-01-01
The authors describe and have used a new afterloading applicator in six patients for primary radiation therapy of endometrial cancer. The first introduction of the applicator was done under general anaesthesia. Dilating the cervical canal to Heger 9 made insertion easier. Prior to application it is advisable to probe the lumen of the uterine cavity with a tube or curette to estimate how far the applicator must be spread open. For brachytherapy it is advantageous to remove necrotic tumour portions. This requires experienced hands to avoid perforation of the uterus. The new afterloading applicator is easy to use, and permits direct contact between the six tubes and the tumour. In conjunction with careful planning with the help of MRI, it provides an optimal system for the treatment of endometrial cancer. (Author)
Robotic-assisted laparoscopic hysterectomy for women with endometrial cancer
DEFF Research Database (Denmark)
Herling, Suzanne Forsyth; Møller, Ann M; Palle, Connie
2017-01-01
INTRODUCTION: Robotic-assisted laparoscopic hysterectomy (RALH) has become a widely used approach for women with endometrial cancer and has replaced laparotomy. It has been questioned if the increased costs are justified by superior surgical outcomes. The aim of the present study was to examine...
Directory of Open Access Journals (Sweden)
Lech Chyczewski
2012-01-01
Full Text Available The objective of this study was to verify the frequency of P53 and BCL-2 immunohistochemical expression in 98 patients with endometrial carcinoma, and to correlate it with clinical stage and patient survival. A significant difference was found regarding the frequency of P53 expression when comparing type I and II tumors (23.7% and 54.5%, respectively; p = 0.006. A positive correlation was observed between P53 immunoexpression and patient survival in type I and II tumors (p = 0.009 and p = 0.036, respectively. BCL-2 expression was significantly more frequent in early clinical stages in both types of endometrial cancer (p < 0.001 and 0.002 and correlated with a decrease in overall survival in type I endometrial cancer (p = 0.014. Thus, the prognostic value of these biomarkers in endometrial cancer needs to be further investigated. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 4, pp. 631–635
Checkpoint inhibitors in endometrial cancer: preclinical rationale and clinical activity.
Mittica, Gloria; Ghisoni, Eleonora; Giannone, Gaia; Aglietta, Massimo; Genta, Sofia; Valabrega, Giorgio
2017-10-27
Treatment of advanced and recurrent endometrial cancer (EC) is still an unmet need for oncologists and gynecologic oncologists. The Cancer Genome Atlas Research Network (TCGA) recently provided a new genomic classification, dividing EC in four subgroups. Two types of EC, the polymerase epsilon (POLE)-ultra-mutated and the microsatellite instability-hyper-mutated (MSI-H), are characterized by a high mutation rate providing the rationale for a potential activity of checkpoint inhibitors. We analyzed all available evidence supporting the role of tumor microenvironment (TME) in EC development and the therapeutic implications offered by immune checkpoint inhibitors in this setting. We performed a review on Pubmed with Mesh keywords 'endometrial cancer' and the name of each checkpoint inhibitor discussed in the article. The same search was operated on clinicaltrial.gov to identify ongoing clinical trials exploring PD-1/PD-L1 and CTLA-4 axis in EC, particularly focusing on POLE-ultra-muted and MSI-H cancer types. POLE-ultra-mutated and MSI-H ECs showed an active TME expressing high number of neo-antigens and an elevated amount of tumor infiltrating lymphocytes (TILs). Preliminary results from a phase-1 clinical trial (KEYNOTE-028) demonstrated antitumor activity of Pembrolizumab in EC. Moreover, both Pembrolizumab and Nivolumab reported durable clinical responses in POLE-ultra-mutated patients. Immune checkpoint inhibitors are an attractive option in POLE-ultra-mutated and MSI-H ECs. Future investigations in these subgroups include combinations of checkpoints inhibitors with chemotherapy and small tyrosine kinase inhibitors (TKIs) to enhance a more robust intra-tumoral immune response.
Kawachi, Asuka; Shimazu, Taichi; Budhathoki, Sanjeev; Sawada, Norie; Yamaji, Taiki; Iwasaki, Motoki; Inoue, Manami; Tsugane, Shoichiro
2018-04-18
Evidence on the association between BMI, height, and endometrial cancer risk, including by subtypes, among Asian populations remains limited. We evaluated the impact of BMI and height on the risk of endometrial cancer, overall and by histological subtype. We prospectively investigated 53 651 Japanese women aged 40-69 years. With an average follow-up duration of 18.6 years, 180 newly diagnosed endometrial cancers were reported, including 119 type 1 and 21 type 2. The association between BMI, height, and endometrial cancer risk was assessed using a Cox proportional hazards regression model with adjustment for potential confounders. Overweight and obesity were associated positively with the risk of endometrial cancer. Compared with BMI of 23.0-24.9 kg/m, hazard ratios (HRs) (95% confidence intervals) were 1.93 (1.17-3.16) for BMI of 27.0-29.9 kg/m and 2.37 (1.20-4.66) for BMI of at least 30.0 kg/m. On analysis by histological subtype, with each increase in BMI of 5 U, the estimated HR of type 1 endometrial cancer increased (HR=1.54, 95% confidence interval: 1.21-1.98), but HR of type 2 endometrial cancer was unaffected. There was no statistically significant association between height and endometrial cancer risk. In conclusion, the risk of endometrial cancer was elevated in women with a BMI of at least 27.0 kg/m. By histological subtype, BMI was associated with type 1, but not type 2 endometrial cancer risk among a population with a relatively low BMI compared with western populations.
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Yang Liu
Full Text Available Novel strategies are necessary to improve chemotherapy response in advanced and recurrent endometrial cancer. Here, we demonstrate that terpenoids present in the Steam Distilled Extract of Ginger (SDGE are potent inhibitors of proliferation of endometrial cancer cells. SDGE, isolated from six different batches of ginger rhizomes, consistently inhibited proliferation of the endometrial cancer cell lines Ishikawa and ECC-1 at IC(50 of 1.25 µg/ml. SDGE also enhanced the anti-proliferative effect of radiation and cisplatin. Decreased proliferation of Ishikawa and ECC-1 cells was a direct result of SDGE-induced apoptosis as demonstrated by FITC-Annexin V staining and expression of cleaved caspase 3. GC/MS analysis identified a total of 22 different terpenoid compounds in SDGE, with the isomers neral and geranial constituting 30-40%. Citral, a mixture of neral and geranial inhibited the proliferation of Ishikawa and ECC-1 cells at an IC(50 10 µM (2.3 µg/ml. Phenolic compounds such as gingerol and shogaol were not detected in SDGE and 6-gingerol was a weaker inhibitor of the proliferation of the endometrial cancer cells. SDGE was more effective in inducing cancer cell death than citral, suggesting that other terpenes present in SDGE were also contributing to endometrial cancer cell death. SDGE treatment resulted in a rapid and strong increase in intracellular calcium and a 20-40% decrease in the mitochondrial membrane potential. Ser-15 of p53 was phosphorylated after 15 min treatment of the cancer cells with SDGE. This increase in p53 was associated with 90% decrease in Bcl2 whereas no effect was observed on Bax. Inhibitor of p53, pifithrin-α, attenuated the anti-cancer effects of SDGE and apoptosis was also not observed in the p53(neg SKOV-3 cells. Our studies demonstrate that terpenoids from SDGE mediate apoptosis by activating p53 and should be therefore be investigated as agents for the treatment of endometrial cancer.
Role of pelvic and para-aortic lymphadenectomy in endometrial cancer: Current evidence
Bogani, Giorgio; Dowdy, Sean C.; Cliby, William A.; Ghezzi, Fabio; Rossetti, Diego; Mariani, Andrea
2015-01-01
The aim of the present review is to summarize the current evidence on the role of pelvic and para-aortic lymphadenectomy in endometrial cancer. In 1988, the International Federation of Obstetrics and Gynecology recommended surgical staging for endometrial cancer patients. However, 25 years later, the role of lymph node dissection remains controversial. Although the findings of two large independent randomized trials suggested that pelvic lymphadenectomy provides only adjunctive morbidity with no clear influence on survival outcomes, the studies have many pitfalls that limit interpretation of the results. Theoretically, lymphadenectomy may help identify patients with metastatic dissemination, who may benefit from adjuvant therapy, thus reducing radiation-related morbidity. Also, lymphadenectomy may eradicate metastatic disease. Because lymphatic spread is relatively uncommon, our main effort should be directed at identifying patients who may potentially benefit from lymph node dissection, thus reducing the rate of unnecessary treatment and associated morbidity. This review will discuss the role of lymphadenectomy in endometrial cancer, focusing on patient selection, extension of the surgical procedure, postoperative outcomes, quality of life and costs. The need for new surgical studies and efficacious systemic drugs is recommended. PMID:24472047
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Chi-Chang Chang
2014-12-01
Full Text Available Endometrial cancer is a common malignancy of the female genital tract. This study demonstrates that Siegesbeckia orientalis ethanol extract (SOE significantly inhibited the proliferation of RL95-2 human endometrial cancer cells. Treating RL95-2 cells with SOE caused cell arrest in the G2/M phase and induced apoptosis of RL95-2 cells by up-regulating Bad, Bak and Bax protein expression and down-regulation of Bcl-2 and Bcl-xL protein expression. Treatment with SOE increased protein expression of caspase-3, -8 and -9 dose-dependently, indicating that apoptosis was through the intrinsic and extrinsic apoptotic pathways. Moreover, SOE was also effective against A549 (lung cancer, Hep G2 (hepatoma, FaDu (pharynx squamous cancer, MDA-MB-231 (breast cancer, and especially on LNCaP (prostate cancer cell lines. In total, 10 constituents of SOE were identified by Gas chromatography-mass analysis. Caryophyllene oxide and caryophyllene are largely responsible for most cytotoxic activity of SOE against RL95-2 cells. Overall, this study suggests that SOE is a promising anticancer agent for treating endometrial cancer.
Association of Metformin Use with Outcomes in Advanced Endometrial Cancer Treated with Chemotherapy.
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Obiageli Ezewuiro
Full Text Available There is increasing evidence that metformin, a commonly used treatment for diabetes, might have the potential to be repurposed as an economical and safe cancer therapeutic. The aim of this study was to determine whether stage III-IV or recurrent endometrial cancer patients who are using metformin during treatment with chemotherapy have improved survival. To test this we analyzed a retrospective cohort of subjects at two independent institutions who received chemotherapy for stage III-IV or recurrent endometrial cancer from 1992 to 2011. Diagnosis of diabetes, metformin use, demographics, endometrial cancer clinico-pathologic parameters, and survival duration were abstracted. The primary outcome was overall survival. The final cohort included 349 patients, 31 (8.9% had diabetes and used metformin, 28 (8.0% had diabetes but did not use metformin, and 291 (83.4% did not have diabetes. The results demonstrate that the median overall survival was 45.6 months for patients with diabetes who used metformin compared to 12.5 months for patients with diabetes who did not use metformin and 28.5 months for patients without diabetes (log-rank test comparing the three groups P = 0.006. In a model adjusted for confounders, the difference in survival between the three groups remained statistically significant (P = 0.023. The improvement in survival among metformin users was not explained by better baseline health status or more aggressive use of chemotherapy. Overall, the findings in this retrospective cohort of endometrial cancer patients with stage III-IV or recurrent disease treated with chemotherapy indicate that patients with diabetes who were concurrently treated with metformin survived longer than patients with diabetes who did not use metformin.
Role of positron emission tomography-computed tomography in endometrial cancer
Erdemoğlu, Evrim; Çerçi, Sevim Süreyya; Erdemoğlu, Ebru; Yalçın, Yakup; Tatar, Burak
2017-01-01
Objective: The efficacy of preoperative 18F-fluoro-D-glucose (18F-FDG) positron emission tomography-computed tomography (PET-CT) in endometrium cancer is controversial. We examined the efficacy of PET-CT and the association between maximum standardized uptake value (SUVmax) and prognostic factors in endometrial cancer. Materials and Methods: Thirty patients with endometrial cancer underwent preoperative 18F-FDG/PET-CT. The patients were treated with abdominal hysterectomy with bilateral salpingo-oophorectomy, and bilateral systemic pelvic lymphadenectomy was planned for all patients; paraaortic lymphadenectomy was performed in patients with intermediate and high risk. Tumor histology, grade, depth of myometrial invasion, maximum tumor diameter, lymphovascular invasion, nodal status, and ovarian/adnexal metastases were recorded. Results: The mean primary tumor diameter was reported smaller in PET-CT and the effect size of PET-CT was -0.60. The kappa value was 0.06 for myometrial invasion. Pelvic lymph node metastasis was reported in 22.2% of patients in PET-CT. However, 3.7% of patients had pelvic lymph node metastasis. The kappa value for pelvic lymph node metastasis was 0.23, and sensitivity, specificity, and positive and negative predictive values were 100%, 80.7%, 16.6%, and 100%, respectively. Paraaortic lymph node metastasis in PET-CT was suspected in 10%. However, paraaortic lymph node metastasis was found in 6.7% in histopathologic analyses. The kappa value was 0.15. The sensitivity, specificity, and positive and negative predictive values of PET-CT for detecting paraaortic lymph node metastases were 100%, 93.7%, 66.6%, and 100%, respectively. Myometrial invasion and tumor diameter were the only important prognostic factors affecting SUVmax. Conclusion: According to our results, PET-CT has a limited role and diagnostic efficacy in endometrial cancer. The indications of FDG/PET-CT in endometrium cancer should be studied further and revised. PMID:29379661
Endometrial cancer: magnetic resonance imaging.
Manfredi, R; Gui, B; Maresca, G; Fanfani, F; Bonomo, L
2005-01-01
Carcinoma of the endometrium is the most common invasive gynecologic malignancy of the female genital tract. Clinically, patients with endometrial carcinoma present with abnormal uterine bleeding. The role of magnetic resonance imaging (MRI) in endometrial carcinoma is disease staging and treatment planning. MRI has been shown to be the most valuable imaging mod-ality in this task, compared with endovaginal ultrasound and computed tomography, because of its intrinsic contrast resolution and multiplanar capability. MRI protocol includes axial T1-weighted images; axial, sagittal, and coronal T2-weighted images; and dynamic gadolinium-enhanced T1-weighted imaging. MR examination is usually performed in the supine position with a phased array multicoil using a four-coil configuration. Endometrial carcinoma is isointense with the normal endometrium and myometrium on noncontrast T1-weighted images and has a variable appearance on T2-weighted images demonstrating heterogeneous signal intensity. The appearance of noninvasive endometrial carcinoma on MRI is characterized by a normal or thickened endometrium, with an intact junctional zone and a sharp tumor-myometrium interface. Invasive endometrial carcinoma is characterized disruption or irregularity of the junctional zone by intermediate signal intensity mass on T2-weighted images. Invasion of the cervical stroma is diagnosed when the low signal intensity cervical stroma is disrupted by the higher signal intensity endometrial carcinoma. MRI in endometrial carcinoma performs better than other imaging modalities in disease staging and treatment planning. Further, the accuracy and the cost of MRI are equivalent to those of surgical staging.
Directory of Open Access Journals (Sweden)
Luan XR
2017-03-01
Full Text Available Xiaorong Luan,1,2 Chunjing Ma,2 Ping Wang,2 Fenglan Lou1 1Nursing College, Shandong University, 2Qilu Hospital of Shandong University, Jinan, People’s Republic of China Abstract: High-mobility group box protein 1 (HMGB1, a nuclear protein that plays a significant role in DNA architecture and transcription, was correlated with the progression of some types of cancer. However, the role of HMGB1 in endometrial cancer cell invasion and metastasis remains unexplored. HMGB1 expression was initially assessed by immunohistochemistry and reverse transcription-quantitative polymerase chain reaction (RT-qPCR in normal endometrial tissue and endometrial carcinoma tissue. High expressions of HMGB1 protein were detected in normal endometrial tissues; however, in endometrial cancer tissues, the expressions of HMGB1 were found to be very weak. Furthermore, HMGB1 expressions were negatively correlated with advanced stage and lymph node metastasis in endometrial cancer. Then by RT-qPCR, Western blot and immunocytochemistry, HMGB1 was also detected in primary cultured endometrial cells and four kinds of endometrial cancer cell lines (Ishikawa, HEC-1A, HEC-1B and KLE. We found that the expression of HMGB1 was much higher in normal endometrial cells than in endometrial cancer cells, and reduced expression levels of HMGB1 were observed especially in the highly metastatic cell lines. Using lentivirus transfection, HMGB1 small hairpin RNA was constructed, and this infected the lowly invasive endometrial cancer cell lines, Ishikawa and HEC-1B. HMGB1 knockdown significantly enhanced the proliferation, invasion and metastasis of endometrial cancer cells and induced the process of epithelial-to-mesenchymal transition. These results can contribute to the development of a new potential therapeutic target for endometrial cancer. Keywords: HMGB1, endometrial cancer, invasion, metastasis, epithelial-to-mesenchymal transition
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Farghaly, S.A.
2013-01-01
Background: Endometrial cancer is the most prevalent cancer of the female genital tract in North America. Minimally invasive laparoscopic-assisted surgery and panniculectomy in obese women with endometrial cancer are associated with an improved lymph node count, and lower rate of incisional complications than laparotomy. Methods: Technique for robot-assisted laparoscopic surgery for obese women with endometrial cancer is detailed. Results: Robot-assisted laparoscopic surgical staging, pelvic and para-aortic lymphadenectomy and panniculectomy allow us to avoid the use of postoperative pelvic radiation which is recommended in women with histopathology high-risk findings: deep myometrial invasion or high grade histology. The procedure has the advantage of three-dimensional vision, ergonomic, intuitive control, and wristed instrument that approximate the motion of the human hand. Conclusion: Robot-assisted laparoscopic surgical staging, and panniculectomy in these patients are a safe, and effective alternative to laparoscopic, and laparotomy surgery. It is an ideal tool for performing the complex oncologic procedures encountered in endometrial cancer staging that requires delicate retroperitoneal, pelvic and para-aortic lymph node dissection, while maintaining the principles of oncologic surgery but in a minimally invasive fashion.
Barranger, Emmanuel; Cortez, Annie; Grahek, Dany; Callard, Patrice; Uzan, Serge; Darai, Emile
2004-03-01
We assessed the feasibility of a laparoscopic sentinel node (SN) procedure based on the combined use of radiocolloid and patent blue labeling in patients with endometrial cancer. Seventeen patients (median age, 69 years) with endometrial cancer of stage I (16 patients) or stage II (1 patient) underwent a laparoscopic SN procedure based on combined radiocolloid and patent blue injected pericervically. After the SN procedure, all patients underwent complete laparoscopic pelvic lymphadenectomy and either laparoscopically assisted vaginal hysterectomy (16 patients) or laparoscopic radical hysterectomy (1 patient). SNs (mean number per patient, 2.6; range, 1-4) were identified in 16 (94.1%) of the 17 patients. Macrometastases were detected in three SNs from two patients by hematoxylin and eosin staining. In three other patients, immunohistochemical analysis identified six micrometastatic SNs and one SN containing isolated tumor cells. No false-negative SN results were observed. An SN procedure based on a combination of radiocolloid and patent blue is feasible in patients with early endometrial cancer. Combined use of laparoscopy and this SN procedure permits minimally invasive management of endometrial cancer.
Lin, Douglas I; Hecht, Jonathan L
2016-06-01
Endometrial cancer is associated with Lynch syndrome in 2% to 6% of cases. Adequate screening may prevent of a second cancer and incident cancers in family members via risk-reducing strategies. The goal of the study was to evaluate the detection rate of Lynch syndrome via a targeted screening approach. In 2009, we incorporated targeted Lynch syndrome screening via immunohistochemistry for MLH1, PMS2, MSH2, and MSH6, followed by MLH1 promoter hypermethylation, in select cases of endometrial carcinoma. Criteria for patient selection included (1) all patients Lynch syndrome. Therefore, targeted screening with combined age and morphology based criteria enriches detection of Lynch syndrome in endometrial cancer. However, the detection rate is lower than the rates from published series that offer universal screening. © The Author(s) 2016.
Gavrilyuk, Oxana; Braaten, Tonje; Skeie, Guri; Weiderpass, Elisabete; Dumeaux, Vanessa; Lund, Eiliv
2014-03-25
Coffee and its compounds have been proposed to inhibit endometrial carcinogenesis. Studies in the Norwegian population can be especially interesting due to the high coffee consumption and increasing incidence of endometrial cancer in the country. A total of 97 926 postmenopausal Norwegian women from the population-based prospective Norwegian Women and Cancer (NOWAC) Study, were included in the present analysis. We evaluated the general association between total coffee consumption and endometrial cancer risk as well as the possible impact of brewing method. Multivariate Cox regression analysis was used to estimate risks, and heterogeneity tests were performed to compare brewing methods. During an average of 10.9 years of follow-up, 462 incident endometrial cancer cases were identified. After multivariate adjustment, significant risk reduction was found among participants who drank ≥8 cups/day of coffee with a hazard ratio of 0.52 (95% confidence interval, CI 0.34-0.79). However, we did not observe a significant dose-response relationship. No significant heterogeneity in risk was found when comparing filtered and boiled coffee brewing methods. A reduction in endometrial cancer risk was observed in subgroup analyses among participants who drank ≥8 cups/day and had a body mass index ≥25 kg/m2, and in current smokers. These data suggest that in this population with high coffee consumption, endometrial cancer risk decreases in women consuming ≥8 cups/day, independent of brewing method.
Cowden syndrome detected by FDG PET/CT in an endometrial cancer patient
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Kang, Yun Hee; Lee, Hye Kyung; Park, Geon
2016-01-01
Cowden syndrome (CS) is a rare autosomal dominant disorder characterized by multiple hamartomas in various tissues and cancers (breast, thyroid, and endometrium). We report CS of the esophagus and gastrointestinal tract that was incidentally detected by positron emission tomography/computed tomography (PET/CT) at postoperative surveillance in an endometrial cancer patient. PET/CT showed mildly increased FDG uptake along the entire esophagus and stomach. Upper GI endoscopy and histologic examination revealed glycogenic acanthosis of the esophagus and several hundred gastric polyps. In our case, increased FDG uptake of the esophageal wall contributed to the diagnosis of CS
Cowden syndrome detected by FDG PET/CT in an endometrial cancer patient
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Kang, Yun Hee; Lee, Hye Kyung [Eulji University Hospital, Daejeon (Korea, Republic of); Park, Geon [Dept. of Radiology, The Catholic University of Korea, Daejeon Saint Mary' s Hospital, Daejeon (Korea, Republic of)
2016-09-15
Cowden syndrome (CS) is a rare autosomal dominant disorder characterized by multiple hamartomas in various tissues and cancers (breast, thyroid, and endometrium). We report CS of the esophagus and gastrointestinal tract that was incidentally detected by positron emission tomography/computed tomography (PET/CT) at postoperative surveillance in an endometrial cancer patient. PET/CT showed mildly increased FDG uptake along the entire esophagus and stomach. Upper GI endoscopy and histologic examination revealed glycogenic acanthosis of the esophagus and several hundred gastric polyps. In our case, increased FDG uptake of the esophageal wall contributed to the diagnosis of CS.
Kempers, Marlies J. E.; Kuiper, Roland P.; Ockeloen, Charlotte W.; Chappuis, Pierre O.; Hutter, Pierre; Rahner, Nils; Schackert, Hans K.; Steinke, Verena; Holinski-Feder, Elke; Morak, Monika; Kloor, Matthias; Buettner, Reinhard; Verwiel, Eugene T. P.; van Krieken, J. Han; Nagtegaal, Iris D.; Goossens, Monique; van der Post, Rachel S.; Niessen, Renee C.; Sijmons, Rolf H.; Kluijt, Irma; Hogervorst, Frans B. L.; Leter, Edward M.; Gille, Johan J. P.; Aalfs, Cora M.; Redeker, Egbert J. W.; Hes, Frederik J.; Tops, Carli M. J.; van Nesselrooij, Bernadette P. M.; van Gijn, Marielle E.; Garcia, Encarna B. Gomez; Eccles, Diana M.; Bunyan, David J.; Syngal, Sapna; Stoffel, Elena M.; Culver, Julie O.; Palomares, Melanie R.; Graham, Tracy; Velsher, Lea; Papp, Janos; Olah, Edith; Chan, Tsun L.; Leung, Suet Y.; van Kessel, Ad Geurts; Kiemeney, Lambertus A. L. M.; Hoogerbrugge, Nicoline; Ligtenberg, Marjolijn J. L.
Background Lynch syndrome is caused by germline mutations in MSH2, MLH1, MSH6, and PMS2 mismatch-repair genes and leads to a high risk of colorectal and endometrial cancer. We previously showed that constitutional 3' end deletions of EPCAM can cause Lynch syndrome through epigenetic silencing of
Fonseca, B M; Correia-da-Silva, G; Teixeira, N A
2018-05-01
Among a variety of phytocannabinoids, Δ 9 -tetrahydrocannabinol (THC) and cannabidiol (CBD) are the most promising therapeutic compounds. Besides the well-known palliative effects in cancer patients, cannabinoids have been shown to inhibit in vitro growth of tumor cells. Likewise, the major endocannabinoids (eCBs), anandamide (AEA) and 2-arachidonoylglycerol (2-AG), induce tumor cell death. The purpose of the present study was to characterize cannabinoid elements and evaluate the effect of cannabinoids in endometrial cancer cell viability. The presence of cannabinoid receptors, transient receptor potential vanilloid 1 (TRPV1), and endocannabinoid-metabolizing enzymes were determined by qRT-PCR and Western blot. We also examined the effects and the underlying mechanisms induced by eCBs and phytocannabinoids in endometrial cancer cell viability. Besides TRPV1, both EC cell lines express all the constituents of the endocannabinoid system. We observed that at concentrations higher than 5 μM, eCBs and CBD induced a significant reduction in cell viability in both Ishikawa and Hec50co cells, whereas THC did not cause any effect. In Ishikawa cells, contrary to Hec50co, treatment with AEA and CBD resulted in an increase in the levels of activated caspase -3/-7, in cleaved PARP, and in reactive oxygen species generation, confirming that the reduction in cell viability observed in the MTT assay was caused by the activation of the apoptotic pathway. Finally, these effects were dependent on TRPV1 activation and intracellular calcium levels. These data indicate that cannabinoids modulate endometrial cancer cell death. Selective targeting of TPRV1 by AEA, CBD, or other stable analogues may be an attractive research area for the treatment of estrogen-dependent endometrial carcinoma. Our data further support the evaluation of CBD and CBD-rich extracts for the potential treatment of endometrial cancer, particularly, that has become non-responsive to common therapies.
Brachytherapy Improves Survival in Stage III Endometrial Cancer With Cervical Involvement
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Bingham, Brian [Department of Radiation Oncology, Vanderbilt University, Nashville, Tennessee (United States); Orton, Andrew; Boothe, Dustin [Department of Radiation Oncology, University of Utah, Salt Lake City, Utah (United States); Stoddard, Greg [Division of Epidemiology, University of Utah, Salt Lake City, Utah (United States); Huang, Y. Jessica; Gaffney, David K. [Department of Radiation Oncology, University of Utah, Salt Lake City, Utah (United States); Poppe, Matthew M., E-mail: Matthew.poppe@hci.utah.edu [Department of Radiation Oncology, University of Utah, Salt Lake City, Utah (United States)
2017-04-01
Purpose: To evaluate the survival benefit of adding vaginal brachytherapy (BT) to pelvic external beam radiation therapy (EBRT) in women with stage III endometrial cancer. Methods and Materials: The National Cancer Data Base was used to identify patients with stage III endometrial cancer from 2004 to 2013. Only women who received adjuvant EBRT were analyzed. Women were grouped according to receipt of BT. Logistic regression modeling was used to identify predictors of receiving BT. Log–rank statistics were used to compare survival outcomes. Cox proportional hazards modeling was used to evaluate the effect of BT on survival. A propensity score–matched analysis was also conducted among women with cervical involvement. Results: We evaluated 12,988 patients with stage III endometrial carcinoma, 39% of whom received EBRT plus BT. Women who received BT were more likely to have endocervical or cervical stromal involvement (odds ratios 2.03 and 1.77; P<.01, respectively). For patients receiving EBRT alone, the 5-year survival was 66% versus 69% with the addition of BT at 5 years (P<.01). Brachytherapy remained significantly predictive of decreased risk of death (hazard ratio 0.86; P<.01) on multivariate Cox regression. The addition of BT to EBRT did not affect survival among women without cervical involvement (P=.84). For women with endocervical or cervical stromal invasion, the addition of BT significantly improved survival (log–rank P<.01). Receipt of EBRT plus BT was associated with improved survival in women with positive and negative surgical margins, and receiving chemotherapy did not alter the benefit of BT. Propensity score–matched analysis results confirmed the benefit of BT among women with cervical involvement (hazard ratio 0.80; P=.01). Conclusions: In this population of women with stage III endometrial cancer the addition of BT to EBRT was associated with an improvement in survival for women with endocervical or cervical stromal invasion.
Brachytherapy Improves Survival in Stage III Endometrial Cancer With Cervical Involvement
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Bingham, Brian; Orton, Andrew; Boothe, Dustin; Stoddard, Greg; Huang, Y. Jessica; Gaffney, David K.; Poppe, Matthew M.
2017-01-01
Purpose: To evaluate the survival benefit of adding vaginal brachytherapy (BT) to pelvic external beam radiation therapy (EBRT) in women with stage III endometrial cancer. Methods and Materials: The National Cancer Data Base was used to identify patients with stage III endometrial cancer from 2004 to 2013. Only women who received adjuvant EBRT were analyzed. Women were grouped according to receipt of BT. Logistic regression modeling was used to identify predictors of receiving BT. Log–rank statistics were used to compare survival outcomes. Cox proportional hazards modeling was used to evaluate the effect of BT on survival. A propensity score–matched analysis was also conducted among women with cervical involvement. Results: We evaluated 12,988 patients with stage III endometrial carcinoma, 39% of whom received EBRT plus BT. Women who received BT were more likely to have endocervical or cervical stromal involvement (odds ratios 2.03 and 1.77; P<.01, respectively). For patients receiving EBRT alone, the 5-year survival was 66% versus 69% with the addition of BT at 5 years (P<.01). Brachytherapy remained significantly predictive of decreased risk of death (hazard ratio 0.86; P<.01) on multivariate Cox regression. The addition of BT to EBRT did not affect survival among women without cervical involvement (P=.84). For women with endocervical or cervical stromal invasion, the addition of BT significantly improved survival (log–rank P<.01). Receipt of EBRT plus BT was associated with improved survival in women with positive and negative surgical margins, and receiving chemotherapy did not alter the benefit of BT. Propensity score–matched analysis results confirmed the benefit of BT among women with cervical involvement (hazard ratio 0.80; P=.01). Conclusions: In this population of women with stage III endometrial cancer the addition of BT to EBRT was associated with an improvement in survival for women with endocervical or cervical stromal invasion.
Dallal, Cher M; Brinton, Louise A; Bauer, Douglas C; Buist, Diana S M; Cauley, Jane A; Hue, Trisha F; Lacroix, Andrea; Tice, Jeffrey A; Chia, Victoria M; Falk, Roni; Pfeiffer, Ruth; Pollak, Michael; Veenstra, Timothy D; Xu, Xia; Lacey, James V
2013-02-01
Endometrial cancer risk is strongly influenced by obesity, but the mechanisms of action remain unclear. Leptin and adiponectin, secreted from adipose tissue, reportedly play a role in such carcinogenic processes as cell proliferation, angiogenesis, and insulin regulation. In this case-control study, nested within the Breast and Bone Follow-up of the Fracture Intervention Trial (n=15,595), we assessed pre-diagnostic serum leptin, total adiponectin, and high-molecular-weight (HMW) adiponectin in relation to endometrial cancer among postmenopausal women. During the 10-year follow-up, 62 incident endometrial cases were identified and matched to 124 controls on age, geographical site, time of fasting blood draw at baseline (1992-1993), and trial participation status. Adipokines and C-peptide were measured by ELISA. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated via conditional logistic regression, with exposures categorized in tertiles (T). Multivariable models considered C-peptide, BMI (kg/m(2)), and estradiol (E2) as potential confounders. Endometrial cancer risk was significantly associated with higher leptin levels, adjusted for E2 and C-peptide (OR(T3 vs T1)=2.96; 95% CI, 1.21-7.25; P trend <0.01). After further adjustment for BMI, the estimates were attenuated and the positive trend was no longer statistically significant (OR(T3 vs T1)=2.11; 95% CI, 0.69-6.44; P trend=0.18). No significant associations were observed with adiponectin or HMW adiponectin and endometrial cancer. Our findings with leptin suggest that the leptin-BMI axis might increase endometrial cancer risk through mechanisms other than estrogen-driven proliferation. Continued exploration of these pathways in larger prospective studies may help elucidate mechanisms underlying observed obesity-endometrial cancer associations.
Dallal, Cher M; Brinton, Louise A; Bauer, Douglas C; Buist, Diana S M; Cauley, Jane A; Hue, Trisha F; LaCroix, Andrea; Tice, Jeffrey A; Chia, Chia; Falk, Roni; Pfeiffer, Ruth; Pollak, Michael; Veenstra, Timothy D; Xu, Xia; Lacey, James V
2014-01-01
Endometrial cancer risk is strongly influenced by obesity, but the mechanisms of action remain unclear. Leptin and adiponectin, secreted from adipose tissue, reportedly play a role in such carcinogenic processes as cell proliferation, angiogenesis, and insulin regulation. In this case–control study, nested within the Breast and Bone Follow-up of the Fracture Intervention Trial (n = 15 595), we assessed pre-diagnostic serum leptin, total adiponectin, and high-molecular-weight (HMW) adiponectin in relation to endometrial cancer among postmenopausal women. During the 10-year follow-up, 62 incident endometrial cases were identified and matched to 124 controls on age, geographical site, time of fasting blood draw at baseline (1992–1993), and trial participation status. Adipokines and C-peptide were measured by ELISA. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated via conditional logistic regression, with exposures categorized in tertiles (T). Multivariable models considered C-peptide, BMI (kg/m2), and estradiol (E2) as potential confounders. Endometrial cancer risk was significantly associated with higher leptin levels, adjusted for E2 and C-peptide (ORT3 vs T1 = 2.96; 95% CI, 1.21–7.25; P trend <0.01). After further adjustment for BMI, the estimates were attenuated and the positive trend was no longer statistically significant (ORT3 vs T1 = 2.11; 95% CI, 0.69–6.44; P trend = 0.18). No significant associations were observed with adiponectin or HMW adiponectin and endometrial cancer. Our findings with leptin suggest that the leptin–BMI axis might increase endometrial cancer risk through mechanisms other than estrogen-driven proliferation. Continued exploration of these pathways in larger prospective studies may help elucidate mechanisms underlying observed obesity–endometrial cancer associations. PMID:23222000
Exome-wide association study of endometrial cancer in a multiethnic population.
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Maxine M Chen
Full Text Available Endometrial cancer (EC contributes substantially to total burden of cancer morbidity and mortality in the United States. Family history is a known risk factor for EC, thus genetic factors may play a role in EC pathogenesis. Three previous genome-wide association studies (GWAS have found only one locus associated with EC, suggesting that common variants with large effects may not contribute greatly to EC risk. Alternatively, we hypothesize that rare variants may contribute to EC risk. We conducted an exome-wide association study (EXWAS of EC using the Infinium HumanExome BeadChip in order to identify rare variants associated with EC risk. We successfully genotyped 177,139 variants in a multiethnic population of 1,055 cases and 1,778 controls from four studies that were part of the Epidemiology of Endometrial Cancer Consortium (E2C2. No variants reached global significance in the study, suggesting that more power is needed to detect modest associations between rare genetic variants and risk of EC.
Jeon, J H; Jeong, K; Moon, H S
2017-01-01
Thickened uterine endometrium with abnormal uterine bleeding highly suggests endometrial hyperplasia or endometrial carcinoma. A case of 35-year-old nulliparous woman came to our department with endometrial mass manifesting as endometrial cancer. Transrectal ultrasonography and magnetic resonance imaging (MRI) showed an 8x6 cm multicystic, ill-defined mass compacted at the uterine endometrium, the anterior wall of the uterus, and 3x3 cm heterogenous mass at the left adnexa. The edometrial mass showed multiple septations with enhancement and low-signal intensity on T2-weighted images. After endometrial biopsy was done and simple hyperplasia without atypia was observed at the histopathologic finding, the patient underwent robot-assisted laparoscopy and diagnosed as adenomyoma at the frozen pathology. After adenomyomectomy, permanent pathologic analysis revealed the same result and she recovered without any complications and responded well to gonadotropin-releasing hormone (GnRH) agonist therapy.
Woo, Sungmin; Kim, Sang Youn; Cho, Jeong Yeon; Kim, Seung Hyup
2017-05-01
To investigate the added value of secondary reports issued by radiologists subspecializing in gynaecologic imaging for determining deep myometrial invasion of endometrial cancer on MRI. Initial (from referring institutions) and secondary (by subspecialized radiologists) interpretations of MRI of 55 patients with endometrial cancer were retrospectively reviewed. A radiologist blinded to clinicopathological information assessed both reports for the presence of deep myometrial invasion. Reference standard was based on hysterectomy specimens. Kappa coefficients (k) were used to measure their concordance. McNemar testing and receiver operating characteristic (ROC) analysis was used to compare sensitivities, specificities and areas under the curves (AUCs). Deep myometrial invasion was present in 25 (45.5 %) patients. Among 27.3 % (15/55; k = 0.458) patients with discrepant results, secondary interpretations were correct in 10 (66.7 %) cases. Sensitivity was higher in secondary than in initial reports (76.0 % vs. 48.0 %, p = 0.039) while no significant difference was seen in specificity (70.0 % vs. 76.7 %, p = 0.668). At ROC analysis, there was a tendency for higher AUCs in secondary reports (0.785 vs 0.669, p = 0.096). Secondary readings of MRI by subspecialized gynaecologic oncologic radiologists may provide incremental value in determining deep myometrial invasion of endometrial cancer. • Deep myometrial invasion is an important prognostic factor in endometrial cancer. • Assessment of deep myometrial invasion is often discrepant between initial and secondary reports. • Secondary reports showed higher sensitivity and accuracy. • Secondary review of MRI may provide incremental value in endometrial cancer patients.
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Galina Lurie
2011-02-01
Full Text Available Overweight and obesity are strongly associated with endometrial cancer. Several independent genome-wide association studies recently identified two common polymorphisms, FTO rs9939609 and MC4R rs17782313, that are linked to increased body weight and obesity. We examined the association of FTO rs9939609 and MC4R rs17782313 with endometrial cancer risk in a pooled analysis of nine case-control studies within the Epidemiology of Endometrial Cancer Consortium (E2C2. This analysis included 3601 non-Hispanic white women with histologically-confirmed endometrial carcinoma and 5275 frequency-matched controls. Unconditional logistic regression models were used to assess the relation of FTO rs9939609 and MC4R rs17782313 genotypes to the risk of endometrial cancer. Among control women, both the FTO rs9939609 A and MC4R rs17782313 C alleles were associated with a 16% increased risk of being overweight (p = 0.001 and p = 0.004, respectively. In case-control analyses, carriers of the FTO rs9939609 AA genotype were at increased risk of endometrial carcinoma compared to women with the TT genotype [odds ratio (OR = 1.17; 95% confidence interval (CI: 1.03-1.32, p = 0.01]. However, this association was no longer apparent after adjusting for body mass index (BMI, suggesting mediation of the gene-disease effect through body weight. The MC4R rs17782313 polymorphism was not related to endometrial cancer risk (per allele OR = 0.98; 95% CI: 0.91-1.06; p = 0.68. FTO rs9939609 is a susceptibility marker for white non-Hispanic women at higher risk of endometrial cancer. Although FTO rs9939609 alone might have limited clinical or public health significance for identifying women at high risk for endometrial cancer beyond that of excess body weight, further investigation of obesity-related genetic markers might help to identify the pathways that influence endometrial carcinogenesis.
The influence of hormone therapies on type I and II endometrial cancer
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Mørch, Lina S.; Kjær, Susanne K.; Keiding, Niels
2016-01-01
identified from the National Cancer Registry: 4,972 Type I tumors and 500 Type II tumors. Incidence rate ratios (RRs) and 95% confidence intervals (Cls) were estimated by Poisson regression. Compared with women never on HT, the RR of endometrial cancer was increased with conjugated estrogen: 4.27 (1...
International Nuclear Information System (INIS)
Park, Sung Bin; Moon, Min Hoan; Sung, Chang Kyu; Oh, Sohee; Lee, Young Ho
2014-01-01
To investigate the optimal imaging delay time of dynamic contrast-enhanced magnetic resonance (MR) imaging in women with endometrial cancer. This prospective single-institution study was approved by the institutional review board, and informed consent was obtained from the participants. Thirty-five women (mean age, 54 years; age range, 29-66 years) underwent dynamic contrast-enhanced MR imaging with a temporal resolution of 25-40 seconds. The signal intensity difference ratios between the myometrium and endometrial cancer were analyzed to investigate the optimal imaging delay time using single change-point analysis. The optimal imaging delay time for appropriate tumour-myometrium contrast ranged from 31.7 to 268.1 seconds. The median optimal imaging delay time was 91.3 seconds, with an interquartile range of 46.2 to 119.5 seconds. The median signal intensity difference ratios between the myometrium and endometrial cancer were 0.03, with an interquartile range of -0.01 to 0.06, on the pre-contrast MR imaging and 0.20, with an interquartile range of 0.15 to 0.25, on the post-contrast MR imaging. An imaging delay of approximately 90 seconds after initiating contrast material injection may be optimal for obtaining appropriate tumour-myometrium contrast in women with endometrial cancer. (orig.)
Outcomes and cost comparisons after introducing a robotics program for endometrial cancer surgery.
Lau, Susie; Vaknin, Zvi; Ramana-Kumar, Agnihotram V; Halliday, Darron; Franco, Eduardo L; Gotlieb, Walter H
2012-04-01
To evaluate the effect of introducing a robotic program on cost and patient outcome. This was a prospective evaluation of clinical outcome and cost after introducing a robotics program for the treatment of endometrial cancer and a retrospective comparison to the entire historical cohort. Consecutive patients with endometrial cancer who underwent robotic surgery (n=143) were compared with all consecutive patients who underwent surgery (n=160) before robotics. The rate of minimally invasive surgery increased from 17% performed by laparoscopy to 98% performed by robotics in 2 years. The patient characteristics were comparable in both eras, except for a higher body mass index in the robotics era (median 29.8 compared with 27.6; Probotics had longer operating times (233 compared with 206 minutes), but fewer adverse events (13% compared with 42%; Probotics compared with the historical group (Can$7,644 compared with Can$10,368 [Canadian dollars]; Psurgery, the short-term recurrence rate appeared lower in the robotics group compared with the historic cohort (11 recurrences compared with 19 recurrences; Probotics for endometrial cancer surgery increased the proportion of patients benefitting from minimally invasive surgery, improved short-term outcomes, and resulted in lower hospital costs. II.
Bruegl, Amanda S; Djordjevic, Bojana; Urbauer, Diana L; Westin, Shannon N; Soliman, Pamela T; Lu, Karen H; Luthra, Rajyalakshmi; Broaddus, Russell R
2014-01-01
Clinical screening criteria, such as young age of endometrial cancer diagnosis and family history of signature cancers, have traditionally been used to identify women with Lynch Syndrome, which is caused by mutation of a DNA mismatch repair gene. Immunohistochemistry and microsatellite instability analysis have evolved as important screening tools to evaluate endometrial cancer patients for Lynch Syndrome. A complicating factor is that 15-20% of sporadic endometrial cancers have immunohistochemical loss of the DNA mismatch repair protein MLH1 and high levels of microsatellite instability due to methylation of MLH1. The PCR-based MLH1 methylation assay potentially resolves this issue, yet many clinical laboratories do not perform this assay. The objective of this study was to determine if clinical and pathologic features help to distinguish sporadic endometrial carcinomas with MLH1 loss secondary to MLH1 methylation from Lynch Syndrome-associated endometrial carcinomas with MLH1 loss and absence of MLH1 methylation. Of 337 endometrial carcinomas examined, 54 had immunohistochemical loss of MLH1. 40/54 had MLH1 methylation and were designated as sporadic, while 14/54 lacked MLH1 methylation and were designated as Lynch Syndrome. Diabetes and deep myometrial invasion were associated with Lynch Syndrome; no other clinical or pathological variable distinguished the 2 groups. Combining Society of Gynecologic Oncology screening criteria with these 2 features accurately captured all Lynch Syndrome cases, but with low specificity. In summary, no single clinical/pathologic feature or screening criteria tool accurately identified all Lynch Syndrome-associated endometrial carcinomas, highlighting the importance of the MLH1 methylation assay in the clinical evaluation of these patients.
Bergadà, Laura; Sorolla, Annabel; Yeramian, Andree; Eritja, Nuria; Mirantes, Cristina; Matias-Guiu, Xavier; Dolcet, Xavier
2013-08-01
Histone deacetylase inhibitors such as Vorinostat display anti-neoplastic activity against a variety of solid tumors. Here, we have investigated the anti-tumoral activity of Vorinostat on endometrial cancer cells. We have found that Vorinostat caused cell growth arrest, loss of clonogenic growth and apoptosis of endometrial cancer cells. Vorinostat-induced the activation of caspase-8 and -9, the initiators caspases of the extrinsic and the intrinsic apoptotic pathways, respectively. Next, we investigated the role of the extrinsic pathway in apoptosis triggered by Vorinostat. We found that Vorinostat caused a dramatic decrease of FLIP mRNA and protein levels. However, overexpression of the long from of FLIP did not block Vorinostat-induced apoptosis. To further investigate the role of extrinsic apoptotic pathway in Vorinostat-induced apoptosis, we performed an shRNA-mediated knock-down of caspase-8. Surprisingly, downregulation of caspase-8 alone caused a marked decrease in clonogenic ability and reduced the growth of endometrial cancer xenografts in vivo, revealing that targeting caspase-8 may be an attractive target for anticancer therapy on endometrial tumors. Furthermore, combination of caspase-8 inhibition and Vorinostat treatment caused an enhancement of apoptotic cell death and a further decrease of clonogenic growth of endometrial cancer cells. More importantly, combination of Vorinostat and caspase-8 inhibition caused a nearly complete inhibition of tumor xenograft growth. Finally, we demonstrate that cell death triggered by Vorinostat alone or in combination with caspase-8 shRNAs was inhibited by the anti-apoptotic protein Bcl-XL. Our results suggest that combinatory therapies using Vorinostat treatment and caspase-8 inhibition can be an effective treatment for endometrial carcinomas. Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Bergadà, Laura; Sorolla, Annabel; Yeramian, Andree; Eritja, Nuria; Mirantes, Cristina; Matias-Guiu, Xavier; Dolcet, Xavier
2013-01-01
Histone deacetylase inhibitors such as Vorinostat display anti‐neoplastic activity against a variety of solid tumors. Here, we have investigated the anti‐tumoral activity of Vorinostat on endometrial cancer cells. We have found that Vorinostat caused cell growth arrest, loss of clonogenic growth and apoptosis of endometrial cancer cells. Vorinostat‐induced the activation of caspase‐8 and ‐9, the initiators caspases of the extrinsic and the intrinsic apoptotic pathways, respectively. Next, we ...
Spontaneous pneumothorax after intensive chemotherapy in endometrial cancer: A rare complication
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Jen-Ruei Chen
2014-06-01
Conclusion: Rapid shrinkage of a pulmonary space-occupying tumor sometimes causes rare but life-threatening spontaneous pneumothoraces. We report the first case of a spontaneous pneumothorax after using paclitaxel plus carboplatin in the treatment of endometrial cancer.
Management of endometrial cancer: issues and controversies.
Bogani, G; Dowdy, S C; Cliby, W A; Ghezzi, F; Rossetti, D; Frigerio, L; Mariani, A
2016-01-01
Although endometrial cancer (EC) is the most common gynecologic cancer in developed countries, several aspects of its management are still controversial. In particular, the need to perform lymphadenectomy represents an important matter of discussion. Because of the discordant results in the literature, it is still not possible to draft any definitive conclusions regarding the therapeutic value of lymph node dissection. The present review discusses the role of lymphadenectomy in the setting of EC, risk factors for lymphatic spread, identification of patients at risk for lymph node dissemination, and the current evidence for adjuvant therapies in patients with positive nodes. Reasons for the difficulty in demonstrating any therapeutic value of pelvic and para-aortic lymphadenectomy are also discussed.
Eggink, F A; Mom, C H; Boll, D; Ezendam, N P M; Kruitwagen, R F P M; Pijnenborg, J M A; van der Aa, M A; Nijman, H W
2017-08-01
Compliance of physicians with guidelines has emerged as an important indicator for quality of care. We evaluated compliance of physicians with adjuvant therapy guidelines for endometrial cancer patients in the Netherlands in a population-based cohort over a period of 10years. Data from all patients diagnosed with endometrial cancer between 2005 and 2014, without residual tumor after surgical treatment, were extracted from the Netherlands Cancer Registry (N=14,564). FIGO stage, grade, tumor type and age were used to stratify patients into risk groups. Possible changes in compliance over time and impact of compliance on survival were assessed. Patients were stratified into low/low-intermediate (52%), high-intermediate (21%) and high (20%) risk groups. Overall compliance with adjuvant therapy guidelines was 85%. Compliance was highest in patients with low/low-intermediate risk (98%, no adjuvant therapy indicated). The lowest compliance was determined in patients with high risk (61%, external beam radiotherapy with/without chemotherapy indicated). Within this group compliance decreased from 64% in 2005-2009 to 57% in 2010-2014. In high risk patients with FIGO stage III serous disease compliance was 55% (chemotherapy with/without radiotherapy indicated) and increased from 41% in 2005-2009 to 66% in 2010-2014. While compliance of physicians with adjuvant therapy guidelines is excellent in patients with low and low-intermediate risk, there is room for improvement in high risk endometrial cancer patients. Eagerly awaited results of ongoing randomized clinical trials may provide more definitive guidance regarding adjuvant therapy for high risk endometrial cancer patients. Copyright © 2017 Elsevier Inc. All rights reserved.
Mandato, Vincenzo Dario; Formisano, Debora; Pirillo, Debora; Ciarlini, Gino; Cerami, Lillo Bruno; Ventura, Alessandro; Spreafico, Lorenzo; Palmieri, Tamara; La Sala, Giovanni Battista; Abrate, Martino
2012-01-01
According to the hub-and-spoke model introduced in the Provincial Healthcare System of Reggio Emilia, early endometrial cancer is treated in peripheral low-volume hospitals (spokes) by general gynecologist, whereas more complex cancers are treated by gynecological oncologists at the main hospital (hub). To guarantee a uniformly high standard of care to all patients with endometrial cancer treated in hub and spoke hospitals of Reggio Emilia Province. The specialists of the 5 hospitals of Reggio Emilia Province instituted an inter hospital and multidisciplinary oncology group to write common and shared guidelines based on evidence-based medicine through the use of clinical audit. They valued the process indicators before and after guidelines introduction identifying the site of improvement and verifying the standard achievement. Diagnostic hysteroscopy use increased significantly from preguideline period, 53%, to postguideline period, 74%. Magnetic resonance use and accuracy increased significantly from preguideline to postguideline periods: 8.1% to 35.3% and 37.3% to 74.7%, respectively. Laparoscopy use increased from 1.6% (preguideline) to 18.6 (postguideline). Early surgical complications decreased from 16% (preguideline) to 9% (postguideline). Radiotherapy use increased from 14.% (preguideline) to 32.3% (postguideline). It is possible for a provincial oncology group to build an oncology network providing an improvement in the assistance of patients with endometrial cancer through the use of clinical audit. Clinical audit made it possible to obtain the full attendance of specialists of various disciplines involved in the treatment of endometrial cancer to optimize response time schematizing process.
Wu, Chien-Tung; Lai, Jung-Nien; Tsai, Yueh-Ting
2014-01-01
Purpose The increased practice of traditional Chinese medicine worldwide has raised concerns regarding herb-drug interactions. We analyzed the usage of Chinese herbal products containing dang-qui and investigated whether dang-qui therapy increases endometrial cancer risk among tamoxifen-treated breast cancer survivors in Taiwan. Methods All patients newly diagnosed with invasive breast cancer who received tamoxifen treatment from January 1, 1998, to December 31, 2008 were selected from the National Health Insurance Research Database. The usage, frequency of service and type of Chinese herbal products containing dang-qui prescribed across the 31,970 survivors were evaluated. Logistic regression method was employed to estimate the odds ratios for utilization of Chinese herbal products containing dang-qui. Cox proportional hazard regression was performed to calculate the hazard ratio of endometrial cancer associated with dang-qui use within the cohort. Results Almost one in two study subjects had used dang-qui. Among 31,938 tamoxifen-treated breast cancer survivors, 157 cases of subsequent endometrial cancer were identified. The hazard ratio for development of endometrial cancer among breast cancer survivors aged 20–79 years who had taken dang-qui after tamoxifen treatment was decreased compared to survivors who had never used dang-qui (HR: 0.61, 95%CI: 0.44–0.84). To minimise potential confounding factors, women with breast cancer in the reproductive age were excluded from further analysis, and the negative relationship between dang-qui consumption and subsequent endometrial cancer among breast cancer survivors aged 55–79 years was still observed, although not significantly (HR: 0.74, 95%CI: 0.46–1.17). Conclusions Dang-qui consumption is common among breast cancer survivors aged 20–79 years and seems decrease the risk of subsequent endometrial cancer after less than a cumulative dose of 7,500 mg of tamoxifen treatment. PMID:25485843
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Maoyong Fu
Full Text Available Endometrial cancer is the most common gynecologic malignancy diagnosed among women in developed countries. One recent biomarker strongly associated with disease progression and survival is epithelial membrane protein-2 (EMP2, a tetraspan protein known to associate with and modify surface expression of certain integrin isoforms. In this study, we show using a xenograft model system that EMP2 expression is necessary for efficient endometrial tumor formation, and we have started to characterize the mechanism by which EMP2 contributes to this malignant phenotype. In endometrial cancer cells, the focal adhesion kinase (FAK/Src pathway appears to regulate migration as measured through wound healing assays. Manipulation of EMP2 levels in endometrial cancer cells regulates the phosphorylation of FAK and Src, and promotes their distribution into lipid raft domains. Notably, cells with low levels of EMP2 fail to migrate and poorly form tumors in vivo. These findings reveal the pivotal role of EMP2 in endometrial cancer carcinogenesis, and suggest that the association of elevated EMP2 levels with endometrial cancer prognosis may be causally linked to its effect on integrin-mediated signaling.
Tricarico, Rossella; Bet, Paola; Ciambotti, Benedetta; Di Gregorio, Carmela; Gatteschi, Beatrice; Gismondi, Viviana; Toschi, Benedetta; Tonelli, Francesco; Varesco, Liliana; Genuardi, Maurizio
2009-02-18
MUTYH-associated polyposis (MAP) is an autosomal recessive condition predisposing to colorectal cancer, caused by constitutional biallelic mutations in the base excision repair (BER) gene MUTYH. Colorectal tumours from MAP patients display an excess of somatic G>T mutations in the APC and KRAS genes due to defective BER function. To date, few extracolonic manifestations have been observed in MAP patients, and the clinical spectrum of this condition is not yet fully established. Recently, one patient with a diagnosis of endometrial cancer and biallelic MUTYH mutations has been described. We here report on two additional unrelated MAP patients with biallelic MUTYH germline mutations who developed endometrioid endometrial carcinoma. The endometrial tumours were evaluated for PTEN, PIK3CA, KRAS, BRAF and CTNNB1 mutations. A G>T transversion at codon 12 of the KRAS gene was observed in one tumour. A single 1bp frameshift deletion of PTEN was observed in the same sample. Overall, these findings suggest that endometrial carcinoma is a phenotypic manifestations of MAP and that inefficient repair of oxidative damage can be involved in its pathogenesis.
Owuor, Theresa O; Reid, Michaela; Reschke, Lauren; Hagemann, Ian; Greco, Suellen; Modi, Zeel; Moley, Kelle H
2018-01-01
Thirty-eight percent of US adult women are obese, meaning that more children are now born of overweight and obese mothers, leading to an increase in predisposition to several adult onset diseases. To explore this phenomenon, we developed a maternal obesity animal model by feeding mice a diet composed of high fat/ high sugar (HF/HS) and assessed both maternal diet and offspring diet on the development of endometrial cancer (ECa). We show that maternal diet by itself did not lead to ECa initiation in wildtype offspring of the C57Bl/6J mouse strain. While offspring fed a HF/HS post-weaning diet resulted in poor metabolic health and decreased uterine weight (regardless of maternal diet), it did not lead to ECa. We also investigated the effects of the maternal obesogenic diet on ECa development in a Diethylstilbestrol (DES) carcinogenesis mouse model. All mice injected with DES had reproductive tract lesions including decreased number of glands, condensed and hyalinized endometrial stroma, and fibrosis and increased collagen deposition that in some mice extended into the myometrium resulting in extensive disruption and loss of the inner and outer muscular layers. Fifty percent of DES mice that were exposed to maternal HF/HS diet developed several features indicative of the initial stages of carcinogenesis including focal glandular and atypical endometrial hyperplasia versus 0% of their Chow counterparts. There was an increase in phospho-Akt expression in DES mice exposed to maternal HF/HS diet, a regulator of persistent proliferation in the endometrium, and no difference in total Akt, phospho-PTEN and total PTEN expression. In summary, maternal HF/HS diet exposure induces endometrial hyperplasia and other precancerous phenotypes in mice treated with DES. This study suggests that maternal obesity alone is not sufficient for the development of ECa, but has an additive effect in the presence of a secondary insult such as DES.
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Tsogzolmaa Dorjgochoo
Full Text Available In vitro studies have demonstrated the role of the BCL-2 family of genes in endometrial carcinogenesis. The role of genetic variants in BCL-2 genes and their interactions with non-genetic factors in the development of endometrial cancer has not been investigated in epidemiological studies.We examined the relationship between BCL-2 gene family variants and endometrial cancer risk among 1,028 patients and 1,922 age-matched community controls from Shanghai, China. We also investigated possible interactions between genetic variants and established risk factors (demographic, lifestyle and clinical. Individuals were genotyped for 86 tagging single nucleotide polymorphisms (SNPs in the BCL2, BAX, BAD and BAK1 genes.Significant associations with endometrial cancer risk were found for 9 SNPs in the BCL2 gene (P trend<0.05 for all. For SNPs rs17759659 and rs7243091 (minor allele for both: G, the associations were independent. The odds ratio was 1.27 (95% CI: 1.04-1.53 for women with AG genotype for the SNP rs17759659 and 1.82 (95% CI: 1.21-2.73 for women with the GG genotype for the SNP rs7243091. No interaction between these two SNPs and established non-genetic risk factors of endometrial cancer was noticed.Genetic polymorphisms in the BCL2 gene may be associated with the risk of endometrial cancer in Chinese women.
Non-Coding RNAs and Endometrial Cancer
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Cristina Vallone
2018-03-01
Full Text Available Non-coding RNAs (ncRNAs are involved in the regulation of cell metabolism and neoplastic transformation. Recent studies have tried to clarify the significance of these information carriers in the genesis and progression of various cancers and their use as biomarkers for the disease; possible targets for the inhibition of growth and invasion by the neoplastic cells have been suggested. The significance of ncRNAs in lung cancer, bladder cancer, kidney cancer, and melanoma has been amply investigated with important results. Recently, the role of long non-coding RNAs (lncRNAs has also been included in cancer studies. Studies on the relation between endometrial cancer (EC and ncRNAs, such as small ncRNAs or micro RNAs (miRNAs, transfer RNAs (tRNAs, ribosomal RNAs (rRNAs, antisense RNAs (asRNAs, small nuclear RNAs (snRNAs, Piwi-interacting RNAs (piRNAs, small nucleolar RNAs (snoRNAs, competing endogenous RNAs (ceRNAs, lncRNAs, and long intergenic ncRNAs (lincRNAs have been published. The recent literature produced in the last three years was extracted from PubMed by two independent readers, which was then selected for the possible relation between ncRNAs, oncogenesis in general, and EC in particular.
2018-03-05
Cancer Survivor; Endometrial Carcinoma; Stage I Uterine Corpus Cancer AJCC v7; Stage IA Uterine Corpus Cancer AJCC v7; Stage IB Uterine Corpus Cancer AJCC v7; Stage II Uterine Corpus Cancer AJCC v7; Stage IIIA Uterine Corpus Cancer AJCC v7
Tumor estrogen content and clinico-morphological and endocrine features of endometrial cancer.
Berstein, L M; Tchernobrovkina, A E; Gamajunova, V B; Kovalevskij, A J; Vasilyev, D A; Chepik, O F; Turkevitch, E A; Tsyrlina, E V; Maximov, S J; Ashrafian, L A; Thijssen, J H H
2003-04-01
To compare estrogen concentrations in endometrial cancer tissue with those in macroscopically normal endometrium and with certain morphological characteristics of the tumor and endocrine parameters in patients. The estradiol content was evaluated by radioimmunoassay after homogenization and extraction in 78 adenocarcinomas (61 from postmenopausal patients). Higher concentrations of estradiol in tumor tissue samples than in macroscopically normal endometrium were found in patients of both reproductive and postmenopausal age. This difference was the same in patients with either endometrial carcinoma type I or type II. No association between tumor steroid receptor levels, estradiol concentrations in blood serum, and timing of menopause with intratumoral estradiol contents was discovered. Estradiol concentrations in tumor tissues correlated positively with the clinical stage of disease and rate of tumor invasion (in patients with peripheric/lower type of fat topography), and negatively with tumor differentiation stage (in patients with central/upper type of fat topography) and the percentage of intact double-stranded DNA in normal endometrium. Tumor estrogen content in endometrial cancer has clinical significance that is modified in the presence of certain endocrine characteristics related to insulin resistance. The role of local estrogen production (aromatase activity) in this setting deserves special study.
Influence of aspirin and non-aspirin NSAID use on ovarian and endometrial cancer
DEFF Research Database (Denmark)
Verdoodt, F.; Kjaer, S. K.; Friis, S.
2017-01-01
Increasing evidence supports a role for aspirin use in reducing the incidence and mortality of several cancer types. This has spurred a new wave of interest in this widely used drug. In this review, we present and evaluate the epidemiologic evidence of the association between the use of aspirin....... Overall, observational studies indicate modest reductions in risk of ovarian and endometrial cancer with aspirin use, whereas the results for non-aspirin NSAID use are equivocal. The strongest inverse associations have been reported for long-term consistent aspirin use, notably among subgroups of users (e.......g., those with high body mass index). Few studies have evaluated the influence of NSAID use on the mortality of ovarian or endometrial cancer, and substantial heterogeneity of study characteristics and results preclude any conclusions. Additional studies of aspirin and non-aspirin NSAID use and ovarian...
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E Chupryna
2017-10-01
Full Text Available Breast cancer can metastasize to a vast array of organs, but in rare cases cancer can form secondary lesions in the uterus and cervix. In our case report we have a 56 years old female with gynaecologic bleeding, bloating, and difficulty in breathing, fatigue, weakness and polyuria. After performing of dilatation and curettage the result was endometrial and cervical metastases which show histopathological and immunohistochemical results suggesting invasive lobular carcinoma of the breast that leads to primary breast cancer. The treatment was estimated on the basis of her status.
Risk of endometrial cancer in women treated with ovary-stimulating drugs for subfertility.
Skalkidou, Alkistis; Sergentanis, Theodoros N; Gialamas, Spyros P; Georgakis, Marios K; Psaltopoulou, Theodora; Trivella, Marialena; Siristatidis, Charalampos S; Evangelou, Evangelos; Petridou, Eleni
2017-03-25
Medical treatment for subfertility principally involves the use of ovary-stimulating agents, including selective oestrogen receptor modulators (SERMs), such as clomiphene citrate, gonadotropins, gonadotropin-releasing hormone (GnRH) agonists and antagonists, as well as human chorionic gonadotropin. Ovary-stimulating drugs may act directly or indirectly upon the endometrium (lining of the womb). Nulliparity and some causes of subfertility are recognized as risk factors for endometrial cancer. To evaluate the association between the use of ovary-stimulating drugs for the treatment of subfertility and the risk of endometrial cancer. A search was performed in CENTRAL, MEDLINE (Ovid) and Embase (Ovid) databases up to July 2016, using a predefined search algorithm. A search in OpenGrey, ProQuest, ClinicalTrials.gov, ZETOC and reports of major conferences was also performed. We did not impose language and publication status restrictions. Cohort and case-control studies reporting on the association between endometrial cancer and exposure to ovary-stimulating drugs for subfertility in adult women were deemed eligible. Study characteristics and findings were extracted by review authors independently working in pairs. Inconsistency between studies was quantified by estimating I 2 . Random-effects (RE) models were used to calculate pooled effect estimates. Separate analyses were performed, comparing treated subfertile women versus general population and/or unexposed subfertile women, to address the superimposition of subfertility as an independent risk factor for endometrial cancer. Nineteen studies were eligible for inclusion (1,937,880 participants). Overall, the quality of evidence was very low, due to serious risk of bias and indirectness (non-randomised studies (NRS), which was reflected on the GRADE assessment.Six eligible studies, including subfertile women, without a general population control group, found that exposure to any ovary-stimulating drug was not associated
Social Cognitive Theory Predictors of Exercise Behavior in Endometrial Cancer Survivors
Basen-Engquist, Karen; Carmack, Cindy L.; Li, Yisheng; Brown, Jubilee; Jhingran, Anuja; Hughes, Daniel C.; Perkins, Heidi Y.; Scruggs, Stacie; Harrison, Carol; Baum, George; Bodurka, Diane C.; Waters, Andrew
2014-01-01
Objective This study evaluated whether social cognitive theory (SCT) variables, as measured by questionnaire and ecological momentary assessment (EMA), predicted exercise in endometrial cancer survivors. Methods One hundred post-treatment endometrial cancer survivors received a 6-month home-based exercise intervention. EMAs were conducted using hand-held computers for 10- to 12-day periods every 2 months. Participants rated morning self-efficacy and positive and negative outcome expectations using the computer, recorded exercise information in real time and at night, and wore accelerometers. At the midpoint of each assessment period participants completed SCT questionnaires. Using linear mixed-effects models, we tested whether morning SCT variables predicted minutes of exercise that day (Question 1) and whether exercise minutes at time point Tj could be predicted by questionnaire measures of SCT variables from time point Tj-1 (Question 2). Results Morning self-efficacy significantly predicted that day’s exercise minutes (pexercise minutes (p=0.0003), but the relationship was attenuated when self-efficacy was included in the model (p=0.4032). Morning negative outcome expectations was not associated with exercise minutes. Of the questionnaire measures of SCT variables, only exercise self-efficacy predicted exercise at the next time point (p=0.003). Conclusions The consistency of the relationship between self-efficacy and exercise minutes over short (same day) and longer (Tj to Tj-1) time periods provides support for a causal relationship. The strength of the relationship between morning self-efficacy and exercise minutes suggest that real-time interventions that target daily variation in self-efficacy may benefit endometrial cancer survivors’ exercise adherence. PMID:23437853
Effect of MRE11 loss on PARP-inhibitor sensitivity in endometrial cancer in vitro.
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Romana Koppensteiner
Full Text Available To evaluate the frequency of MRE11/RAD50/NBS1 (MRN-complex loss of protein expression in endometrial cancers (EC and to determine whether loss of MRE11 renders the cancer cells sensitive to Poly(ADP-ribose polymerase (PARP-inhibitory treatment.MRN expression was examined in 521 samples of endometrial carcinomas and in 10 cancer cell lines. A putative mutation hotspot in the form of an intronic poly(T allele in MRE11 was sequenced in selected cases (n = 26. Sensitivity to the PARP-inhibitor, BMN673 was tested in colony formation assays before and after MRE11 silencing using siRNA. Homologous recombination (HR DNA repair was evaluated by RAD51-foci formation assay upon irradiation and drug treatment.Loss of MRE11 protein was found in 30.7% of EC tumours and significantly associated with loss of RAD50, NBS1 and mismatch repair protein expression. One endometrial cell line showed a markedly reduced MRE11 expression due to a homozygous poly(T mutation of MRE11, thereby exhibiting an increased sensitivity to BMN673. MRE11 depletion sensitizes MRE11 expressing EC cell lines to the treatment with BMN673. The increased sensitivity to PARP-inhibition correlates with reduced RAD51 foci formation upon ionizing radiation in MRE11-depleted cells.Loss of the MRE11 protein predicts sensitivity to PARP-inhibitor sensitivity in vitro, defining it as an additional synthetic lethal gene with PARP. The high incidence of MRE11 loss in ECs can be potentially exploited for PARP-inhibitor therapy. Furthermore, MRE11 protein expression using immunohistochemistry could be investigated as a predictive biomarker for PARP-inhibitor treatment.
Clinical value of FDG-PET in the follow up of post-operative patients with endometrial cancer
International Nuclear Information System (INIS)
Saga, Tsuneo; Higashi, Tatsuya; Ishimori, Takayoshi
2003-01-01
The clinical usefulness of FDG-PET in the follow up of post-operative patients with endometrial cancer was retrospectively evaluated. Twenty-one post-operative patients with endometrial cancer received 30 FDG-PET examinations to evaluate recurrence or response to treatment. The findings of FDG-PET were compared with their serum levels of tumor markers, CT and/or MRI findings, and the final outcome. Results of FDG-PET were also correlated with the clinical course of each patient. In detecting recurrent lesions and evaluating treatment responses, FDG-PET, with the help in anatomic information by CT/MRI, showed better diagnostic ability (sensitivity 100.0%, specificity 88.2%, accuracy 93.3%) compared with combined conventional imaging (sensitivity 84.6%, specificity 85.7%, accuracy 85.0%) and tumor markers (sensitivity 100.0%, specificity 70.6%, accuracy 83.3%). FDG-PET had no false-negative results, suggesting the possibility of its use as the first-line examination in a patient's follow-up. FDG-PET could detect unknown lesions in 4 cases, and, as reported for other malignancies, FDG-PET affected the patient management in one-third of the cases. Furthermore, the results of FDG-PET correlated well with the clinical outcome of the patients, with patients with negative PET results tending to show disease-free courses. These results suggest that, despite the limited number of patients studied, FDG-PET was accurate in detecting recurrence and evaluating therapeutic response, and could afford important information in the management of post-operative patients with endometrial cancer. FDG-PET also appeared to have a possibility to predict the outcome of each patient. (author)
Schouten, L.J.; Goldbohm, R.A.; Brandt, P.A. van den
2004-01-01
Although obesity is an established risk factor for endometrial cancer, evidence linking risk to height, weight change since age 20, and physical activity is limited. In this case-cohort study, 62 573 women from The Netherlands Cohort Study on Diet and Cancer were followed up from 1986 to 1995, and
Tas, Emre E.; Yavuz, Ayse F.
2017-01-01
Objectives: To determine the associations between serum cancer antigen 15-3 levels and prognostic factors in patients with endometrial carcinomas. Additionally, we investigated the clinical utility of serum cancer antigen 15-3 levels in the selection of low-risk patients with endometrioid type, tumor size <2 cm, myometrial invasion ≤50%, and histological grade 1-2. Methods: Ninety-six patients, who were surgically staged at Ankara Yildirim Beyazit University, Ankara, Turkey, between 2007 and 2016, were retrospectively analyzed. Demographic, clinical, and surgical characteristics were retrieved from the patients’ hospital records. A p<0.05 was considered significant. Results: Fifteen patients had advanced (≥Stage II) disease, 14 patients had Type 2 histology, 20 patients had Grade 3 tumors, 23 patients had lymphovascular space invasion, and 10 patients had positive lymph node involvement. Serum cancer antigen 15-3 levels were significantly higher in patients with advanced (≥Stage II) disease, Type 2 histology, Grade 3 tumors, lymp°hovascular space invasion, and positive lymph node involvement (p<0.05). Serum cancer antigen 15-3 levels were also significantly correlated with tumor size (p=0.006). Serum cancer antigen 15-3 levels were significantly lower (95% confidence interval: 0.57−0.79; p=0.03) in low-risk patients compared to other endometrial carcinoma patients. A cutoff of 25.0 IU/mL was used to identify high-risk patients with a specificity of 100%. Conclusion: Serum cancer antigen 15-3 levels significantly correlated with prognostic factors and were a useful diagnostic tool for endometrial carcinomas. PMID:29114696
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Emre E. Tas
2017-11-01
Full Text Available Objectives: To determine the associations between serum cancer antigen 15-3 levels and prognostic factors in patients with endometrial carcinomas. Additionally, we investigated the clinical utility of serum cancer antigen 15-3 levels in the selection of low-risk patients with endometrioid type, tumor size less than 2 cm, myometrial invasion ≤50%, and histological grade 1-2. Methods: Ninety-six patients, who were surgically staged at Ankara Yildirim Beyazit University, Ankara, Turkey, between 2007 and 2016, were retrospectively analyzed. Demographic, clinical, and surgical characteristics were retrieved from the patients’ hospital records. A p less than 0.05 was considered significant. Results: Fifteen patients had advanced (≥Stage II disease, 14 patients had Type 2 histology, 20 patients had Grade 3 tumors, 23 patients had lymphovascular space invasion, and 10 patients had positive lymph node involvement. Serum cancer antigen 15-3 levels were significantly higher in patients with advanced (≥Stage II disease, Type 2 histology, Grade 3 tumors, lymphovascular space invasion, and positive lymph node involvement (p less than 0.05. Serum cancer antigen 15-3 levels were also significantly correlated with tumor size (p=0.006. Serum cancer antigen 15-3 levels were significantly lower (95% confidence interval: 0.57−0.79; p=0.03 in low-risk patients compared to other endometrial carcinoma patients. A cutoff of 25.0 IU/mL was used to identify high-risk patients with a specificity of 100%. Conclusion: Serum cancer antigen 15-3 levels significantly correlated with prognostic factors and were a useful diagnostic tool for endometrial carcinomas.
Wright, Jason D; Havrilesky, Laura J; Cohn, David E; Huang, Yongmei; Rathbun, Jill; Rice, Laurel W; Brown, Carol L; Alvarez, Ronald D; Ko, Emily M
2018-05-01
To design an endometrial cancer (EC) alternative payment (ECAP) model focused on surgical management of EC, as well as identify drivers of cost in order to develop opportunities for cost-savings while maintaining quality of care. National practice patterns and reimbursements were compared between private payers (MarketScan data, years 2009-13) and public payers (Medicare, year 2014) of EC patients who underwent hysterectomy. An episode of care for EC included the hysterectomy, stratified by surgical approach (laparotomy versus robotic versus laparoscopy), and in- and outpatient reimbursements from 30days preoperatively to 60days postoperatively. Reimbursements were categorized into cost centers. A decision model informed modifiable components influencing overall reimbursements for EC surgical care. Variations in length of stay (LOS), emergency department (ED visits), and readmissions were analyzed to create an optimal care model. A total of MarketScan (n=29,558) and Medicare (n=377) patients were included. Mean total reimbursement for an episode of care was $19,183 (SD $10,844) for Medicare and $30,839 (SD $19,911) for MarketScan. Mean reimbursements were greatest for abdominal cases in Medicare ($25,553; SD $11,870) and MarketScan ($35,357; SD $21,670), followed by robotic and laparoscopic. Among MarketScan patients, 7.6% of women were readmitted within 60days after surgery and 11.7% had an evaluation in the ED. The median reimbursement per patient for readmission was $14,474 (IQR $8584 to $26,149), and for ED visit was $6327 (IQR $1369 to $29,153). In an optimized care model, increasing the rate of minimally invasive surgery by 5% while reducing LOS by 10% and ED visits/readmissions by 10%, lowered the average case reimbursement by $903 (2.9%) for MarketScan and $1243 (5.9%) for Medicare. An ECAP model demonstrates that reimbursements vary by public versus commercial payers in the U.S. for the surgical management of endometrial cancer patients, and that
Validated Competing Event Model for the Stage I-II Endometrial Cancer Population
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Carmona, Ruben; Gulaya, Sachin; Murphy, James D. [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Rose, Brent S. [Harvard Radiation Oncology Program, Harvard Medical School, Boston, Massachusetts (United States); Wu, John; Noticewala, Sonal [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); McHale, Michael T. [Department of Reproductive Medicine, Division of Gynecologic Oncology, University of California San Diego, La Jolla, California (United States); Yashar, Catheryn M. [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Vaida, Florin [Department of Family and Preventive Medicine, Biostatistics and Bioinformatics, University of California San Diego Medical Center, San Diego, California (United States); Mell, Loren K., E-mail: lmell@ucsd.edu [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States)
2014-07-15
Purpose/Objectives(s): Early-stage endometrial cancer patients are at higher risk of noncancer mortality than of cancer mortality. Competing event models incorporating comorbidity could help identify women most likely to benefit from treatment intensification. Methods and Materials: 67,397 women with stage I-II endometrioid adenocarcinoma after total hysterectomy diagnosed from 1988 to 2009 were identified in Surveillance, Epidemiology, and End Results (SEER) and linked SEER-Medicare databases. Using demographic and clinical information, including comorbidity, we sought to develop and validate a risk score to predict the incidence of competing mortality. Results: In the validation cohort, increasing competing mortality risk score was associated with increased risk of noncancer mortality (subdistribution hazard ratio [SDHR], 1.92; 95% confidence interval [CI], 1.60-2.30) and decreased risk of endometrial cancer mortality (SDHR, 0.61; 95% CI, 0.55-0.78). Controlling for other variables, Charlson Comorbidity Index (CCI) = 1 (SDHR, 1.62; 95% CI, 1.45-1.82) and CCI >1 (SDHR, 3.31; 95% CI, 2.74-4.01) were associated with increased risk of noncancer mortality. The 10-year cumulative incidences of competing mortality within low-, medium-, and high-risk strata were 27.3% (95% CI, 25.2%-29.4%), 34.6% (95% CI, 32.5%-36.7%), and 50.3% (95% CI, 48.2%-52.6%), respectively. With increasing competing mortality risk score, we observed a significant decline in omega (ω), indicating a diminishing likelihood of benefit from treatment intensification. Conclusion: Comorbidity and other factors influence the risk of competing mortality among patients with early-stage endometrial cancer. Competing event models could improve our ability to identify patients likely to benefit from treatment intensification.
Validated Competing Event Model for the Stage I-II Endometrial Cancer Population
International Nuclear Information System (INIS)
Carmona, Ruben; Gulaya, Sachin; Murphy, James D.; Rose, Brent S.; Wu, John; Noticewala, Sonal; McHale, Michael T.; Yashar, Catheryn M.; Vaida, Florin; Mell, Loren K.
2014-01-01
Purpose/Objectives(s): Early-stage endometrial cancer patients are at higher risk of noncancer mortality than of cancer mortality. Competing event models incorporating comorbidity could help identify women most likely to benefit from treatment intensification. Methods and Materials: 67,397 women with stage I-II endometrioid adenocarcinoma after total hysterectomy diagnosed from 1988 to 2009 were identified in Surveillance, Epidemiology, and End Results (SEER) and linked SEER-Medicare databases. Using demographic and clinical information, including comorbidity, we sought to develop and validate a risk score to predict the incidence of competing mortality. Results: In the validation cohort, increasing competing mortality risk score was associated with increased risk of noncancer mortality (subdistribution hazard ratio [SDHR], 1.92; 95% confidence interval [CI], 1.60-2.30) and decreased risk of endometrial cancer mortality (SDHR, 0.61; 95% CI, 0.55-0.78). Controlling for other variables, Charlson Comorbidity Index (CCI) = 1 (SDHR, 1.62; 95% CI, 1.45-1.82) and CCI >1 (SDHR, 3.31; 95% CI, 2.74-4.01) were associated with increased risk of noncancer mortality. The 10-year cumulative incidences of competing mortality within low-, medium-, and high-risk strata were 27.3% (95% CI, 25.2%-29.4%), 34.6% (95% CI, 32.5%-36.7%), and 50.3% (95% CI, 48.2%-52.6%), respectively. With increasing competing mortality risk score, we observed a significant decline in omega (ω), indicating a diminishing likelihood of benefit from treatment intensification. Conclusion: Comorbidity and other factors influence the risk of competing mortality among patients with early-stage endometrial cancer. Competing event models could improve our ability to identify patients likely to benefit from treatment intensification
Obama, Kyoko; Maru, Mitsue; Maeda, Rumi; Kubota, Toshiro
2015-09-30
To examine the relationship between cancer-related fatigue (CRF) and physical activity in daily living in premenopausal disease-free cervical and endometrial cancer survivors. A physical activity monitor was used to collect objective data on daily physical activity. CRF and related variables were measured using self-report scales in a cross-sectional manner. The average age was 44.9 years among 64 women. The higher CRF group comprised 22 women (34%), 10% of whom had severe fatigue. The participants had higher physical activity levels compared with the findings in previous studies, and reported an average of 40 min/day of moderate to vigorous activity. Moderate to vigorous levels of physical activity were derived from essential social activities rather than leisure time exercise. There were no significant differences in physical activity levels between the lower and higher CRF groups. Our study results suggested that the higher level of physical activity in daily living itself had no relationship with decreasing CRF among premenopausal cervical and endometrial cancer survivors. It would be better to focus on cognitive and psychological factors before introducing physical activity programs and be careful of the characteristics of the participants' physical activity among this population in daily basis.
Directory of Open Access Journals (Sweden)
Hei-Yu Lau
2015-10-01
Conclusion: Preservation of bilateral ovaries does not increase cancer-related mortality. A more conservative approach to surgical staging may be considered in premenopausal women with early-stage endometrial cancer without risk factors.
A new clinical trial is testing ONC201, an investigational drug that in laboratory studies has been shown to kill breast and endometrial cancer cells most likely by destroying mitochondria within the tumor cells. Mitochondria are the “powerhouse” of the cell, and blocking its activity may kill tumor cells and shrink tumors in human patients.
Radiation therapy for endometrial cancer in patients treated for postoperative recurrence
International Nuclear Information System (INIS)
Hart, Kimberly B.; Han, Ihn; Shamsa, Falah; Court, Wayne S.; Chuba, Paul; Deppe, Gunter; Malone, John; Christensen, Carl; Porter, Arthur T.
1998-01-01
Purpose: To retrospectively evaluate the outcome and risk factors in patients treated with radiation for endometrial cancer at time of recurrence. Materials and Methods: Three hundred ninety-nine women were treated with radiation therapy for endometrial cancer at KCI/WSU from January 1980 to December 1994. Of these, 26 patients treated primarily with surgery received radiation therapy at the time of recurrence. Median time to recurrence after surgery was 8 months, with all recurrences occurring within 24 months. Twenty-four patients had recurrences in the vaginal cuff, vagina, or pelvis. These patients received external-beam radiation to the pelvis (45.00-50.40 Gy) and periaortic lymph nodes (45.00-50.00 Gy), along with a boost given by external-beam radiation or brachytherapy (16.00-30.00 Gy). Mean follow-up was 15 months (range 1-85 months). Results: The 2-year survival was 50% and median survival was 16 months (survival range 1-85 months). Of 26 patients, 54% (14) failed locally following radiation therapy. Factors indicative of poor survival included histology (sarcoma, poorly differentiated adenocarcinoma), grade, and lymph node positivity. Histological differentiation influenced local control; lymphovascular space invasion was of borderline significance with regard to local control. Conclusion: Local control and survival for surgically treated endometrial cancer patients who receive radiation at the time of recurrence are poor, with the exception of those patients with recurrent disease limited to the vagina. Early detection of recurrence may improve outcome. Pathologic risk factors may identify those patients at risk for extrapelvic recurrence. Alternative treatment modalities need to be developed for this high-risk group of patients
Surgical Treatment of Recurrent Endometrial Cancer: Time for a Paradigm Shift.
Papadia, Andrea; Bellati, Filippo; Ditto, Antonino; Bogani, Giorgio; Gasparri, Maria Luisa; Di Donato, Violante; Martinelli, Fabio; Lorusso, Domenica; Benedetti-Panici, Pierluigi; Raspagliesi, Francesco
2015-12-01
Although surgery represents the cornerstone treatment of endometrial cancer at initial diagnosis, scarce data are available in recurrent setting. The purpose of this study was to review the outcome of surgery in these patients. Medical records of all patients undergoing surgery for recurrent endometrial cancer at NCI Milano between January 2003 and January 2014 were reviewed. Survival was determined from the time of surgery for recurrence to last follow-up. Survival was estimated using Kaplan-Meier methods. Differences in survival were analyzed using the log-rank test. The Fisher's exact test was used to compare optimal versus suboptimal cytoreduction against possible predictive factors. Sixty-four patients were identified. Median age was 66 years. Recurrences were multiple in 38 % of the cases. Optimal cytoreduction was achieved in 65.6 %. Median OR time was 165 min, median postoperative hemoglobin drop was 2.4 g/dl, and median length hospital stay was 5.5 days. Eleven patients developed postoperative complications, but only four required surgical management. Estimated 5-year progression-free survival (PFS) was 42 and 19 % in optimally and suboptimally cytoreduced patients, respectively. At multivariate analysis, only residual disease was associated with PFS. Estimated 5-year overall survival (OS) was 60 and 30 % in optimally and suboptimally cytoreduced patients, respectively. At multivariate analysis, residual disease and histotype were associated with OS. At multivariate analysis, only performance status was associated with optimal cytoreduction. Secondary cytoreduction in endometrial cancer is associated with long PFS and OS. The only factors associated with improved long-term outcome are the absence of residual disease at the end of surgical resection and histotype.
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Du, Gui-Qiang; Zhou, Long; Chen, Xiao-Yue [Department of Obstetrics and Gynecology, The International Peace Maternity and Child Health Hospital of the China Welfare Institute Affiliated to Shanghai Jiao Tong University, 910, Hengshan Road, Shanghai (China); Wan, Xiao-Ping, E-mail: wanxiaoping61@126.com [Department of Obstetrics and Gynecology, The International Peace Maternity and Child Health Hospital of the China Welfare Institute Affiliated to Shanghai Jiao Tong University, 910, Hengshan Road, Shanghai (China); He, Yin-Yan [Department of Obstetrics and Gynecology, Shanghai First People' s Hospital, Shanghai Jiao Tong University, Shanghai (China)
2012-04-06
Highlights: Black-Right-Pointing-Pointer We assessed hydroxytamoxifen (OHT) effects in two endometrial cancer cell lines. Black-Right-Pointing-Pointer GPR30 mediates the proliferative effects induced by OHT. Black-Right-Pointing-Pointer GPR30 mediates the invasive effects induced by OHT. Black-Right-Pointing-Pointer GPR30 expression was up-regulated by OHT in endometrial cancer cell line. -- Abstract: The selective ER modulator tamoxifen (TAM) is the most widely used ER antagonist for treatment of women with hormone-dependent breast tumor. However, long-term treatment is associated with an increased risk of endometrial cancer. The aim of the present study was to demonstrate new insight into the role of G-protein coupled receptor 30 (GPR30) in the activity of TAM, which promoted endometrial cancer. In endometrial cancer cell lines ISHIKAWA and KLE, the potential of 4-hydroxytamoxifen (OHT), the active metabolite of TAM, 17{beta}-estradiol (E2) and G1, a non-steroidal GPR30-specific agonist to promote cell proliferation and invasion was evaluated. All agents above induced high proliferative and invasive effects, while the down-regulation of GPR30 or the interruption of MAPK signal pathway partly or completely prevented the action of the regent. Moreover, the RNA and protein expression of GPR30 was up-regulated by G1, E2 or OHT in both cell lines. The present study provided a new insight into the mechanism involved in the agonistic activity exerted by TAM in the uterus.
International Nuclear Information System (INIS)
Du, Gui-Qiang; Zhou, Long; Chen, Xiao-Yue; Wan, Xiao-Ping; He, Yin-Yan
2012-01-01
Highlights: ► We assessed hydroxytamoxifen (OHT) effects in two endometrial cancer cell lines. ► GPR30 mediates the proliferative effects induced by OHT. ► GPR30 mediates the invasive effects induced by OHT. ► GPR30 expression was up-regulated by OHT in endometrial cancer cell line. -- Abstract: The selective ER modulator tamoxifen (TAM) is the most widely used ER antagonist for treatment of women with hormone-dependent breast tumor. However, long-term treatment is associated with an increased risk of endometrial cancer. The aim of the present study was to demonstrate new insight into the role of G-protein coupled receptor 30 (GPR30) in the activity of TAM, which promoted endometrial cancer. In endometrial cancer cell lines ISHIKAWA and KLE, the potential of 4-hydroxytamoxifen (OHT), the active metabolite of TAM, 17β-estradiol (E2) and G1, a non-steroidal GPR30-specific agonist to promote cell proliferation and invasion was evaluated. All agents above induced high proliferative and invasive effects, while the down-regulation of GPR30 or the interruption of MAPK signal pathway partly or completely prevented the action of the regent. Moreover, the RNA and protein expression of GPR30 was up-regulated by G1, E2 or OHT in both cell lines. The present study provided a new insight into the mechanism involved in the agonistic activity exerted by TAM in the uterus.
Interventions for weight reduction in obesity to improve survival in women with endometrial cancer.
Kitson, Sarah; Ryan, Neil; MacKintosh, Michelle L; Edmondson, Richard; Duffy, James Mn; Crosbie, Emma J
2018-02-01
Diagnoses of endometrial cancer are increasing secondary to the rising prevalence of obesity. Obesity plays an important role in promoting the development of endometrial cancer, by inducing a state of unopposed oestrogen excess, insulin resistance and inflammation. It also affects treatment, increasing the risk of surgical complications and the complexity of radiotherapy planning, and may additionally impact on subsequent survival. Weight-loss interventions have been associated with improvements in breast and colorectal cancer-specific survival as well as a reduction in the risk of cardiovascular disease, a frequent cause of death in endometrial cancer survivors. To determine the impact of weight-loss interventions, in addition to standard management of endometrial cancer, on overall survival and the frequency of adverse events.Secondary objectives include an assessment of weight-loss interventions on endometrial cancer-specific survival, weight loss achieved, cardiovascular event frequency and quality of life both overall and stratified according to patient body mass index (BMI), where possible. This review searched Cochrane Central Register of Controlled Trials, MEDLINE, Embase and reference lists of articles, trial registries, and international gynaecological oncology conference abstracts from inception to January 2018. Randomised controlled trials (RCTs) of interventions to facilitate weight loss in overweight or obese women undergoing treatment for, or previously treated for, endometrial cancer were selected. Two review authors independently selected studies, assessed trial quality, and extracted data with disagreements resolved by a third review author. Study authors were contacted to obtain missing data, including details of any adverse events. We included three RCTs in the review, randomising a total of 161 overweight and obese women with endometrial cancer. All studies compared combined behavioural and lifestyle interventions to facilitate weight loss
The Risk of Extra-colonic, Extra-endometrial Cancer in the Lynch Syndrome
Watson, Patrice; Vasen, Hans F.A.; Mecklin, Jukka-Pekka; Bernstein, Inge; Aarnio, Markku; Järvinen, Heikki J.; Myrhøj, Torben; Sunde, Lone; Wijnen, Juul T.; Lynch, Henry T.
2009-01-01
Persons with the Lynch syndrome (LS) are at high risk for cancer, including cancers of the small bowel, stomach, upper urologic tract (renal pelvis and ureter), ovary, biliary tract, and brain tumors, in addition to the more commonly observed colorectal and endometrial cancers. Cancer prevention strategies for these less-common cancers require accurate, age-specific risk estimation. We pooled data from four LS research centers in a retrospective cohort study, to produce absolute incidence estimates for these cancer types, and to evaluate several potential risk modifiers. After elimination of 135 persons missing crucial information, cohort included 6041 members of 261 families with LS-associated MLH1 or MSH2 mutations. All were either mutation carriers by test, probable mutation carriers (endometrial/colorectal cancer-affected), or first-degree relatives of these. Among mutation carriers and probable carriers, urologic tract cancer (N=98) had an overall lifetime risk (to age 70) of 8.4% (95%CI: 6.6–10.8); risks were higher in males (p<0.02) and members of MSH2 families (p<0.0001). Ovarian cancer (N=72) had an lifetime risk of 6.7% (95%CI: 5.3–9.1); risks were higher in women born after the median year of birth (p<0.008) and in members of MSH2 families (p<0.006). Brain tumors and cancers of the small bowel, stomach, breast, and biliary tract were less common. Urologic tract cancer and ovarian cancer occur frequently enough in some LS subgroups to justify trials to evaluate promising prevention interventions. Other cancer types studied occur too infrequently to justify strenuous cancer control interventions. PMID:18398828
小濵, 京子; 丸, 光惠; 前田, 留美; 久保田, 俊郎
2015-01-01
Purpose: To examine the relationship between cancer-related fatigue (CRF) and physical activity in daily living in premenopausal disease-free cervical and endometrial cancer survivors. Methods: A physical activity monitor was used to collect objective data on daily physical activity. CRF and related variables were measured using self-report scales in a cross-sectional manner. Results: The average age was 44.9 years among 64 women. The higher CRF group comprised 22 women (34%), 10% of whom had...
Xiong, Siyuan; Cheng, Jung-Chien; Klausen, Christian; Zhao, Jianfang; Leung, Peter C K
2016-09-20
PTEN acts as a tumor suppressor primarily by antagonizing the PI3K/AKT signaling pathway. PTEN is frequently mutated in human cancers; however, in type II endometrial cancers its mutation rate is very low. Overexpression of TGF-β1 and its receptors has been reported to correlate with metastasis of human cancers and reduced survival rates. Although TGF-β1 has been shown to regulate PTEN expression through various mechanisms, it is not yet known if the same is true in type II endometrial cancer. In the present study, we show that treatment with TGF-β1 stimulates the migration of two type II endometrial cancer cell lines, KLE and HEC-50. In addition, TGF-β1 treatment down-regulates both mRNA and protein levels of PTEN. Overexpression of PTEN or inhibition of PI3K abolishes TGF-β1-stimulated cell migration. TGF-β1 induces SMAD2/3 phosphorylation and knockdown of common SMAD4 inhibits the suppressive effects of TGF-β1 on PTEN mRNA and protein. Interestingly, TGF-β1 induces ERK1/2 phosphorylation and pre-treatment with a MEK inhibitor attenuates the suppression of PTEN protein, but not mRNA, by TGF-β1. This study provides important insights into the molecular mechanisms mediating TGF-β1-induced down-regulation of PTEN and demonstrates an important role of PTEN in the regulation of type II endometrial cancer cell migration.
Kitchener, H; Swart, A M C; Qian, Q; Amos, C; Parmar, M K B
2009-01-10
Hysterectomy and bilateral salpingo-oophorectomy (BSO) is the standard surgery for stage I endometrial cancer. Systematic pelvic lymphadenectomy has been used to establish whether there is extra-uterine disease and as a therapeutic procedure; however, randomised trials need to be done to assess therapeutic efficacy. The ASTEC surgical trial investigated whether pelvic lymphadenectomy could improve survival of women with endometrial cancer. From 85 centres in four countries, 1408 women with histologically proven endometrial carcinoma thought preoperatively to be confined to the corpus were randomly allocated by a minimisation method to standard surgery (hysterectomy and BSO, peritoneal washings, and palpation of para-aortic nodes; n=704) or standard surgery plus lymphadenectomy (n=704). The primary outcome measure was overall survival. To control for postsurgical treatment, women with early-stage disease at intermediate or high risk of recurrence were randomised (independent of lymph-node status) into the ASTEC radiotherapy trial. Analysis was by intention to treat. This study is registered, number ISRCTN 16571884. After a median follow-up of 37 months (IQR 24-58), 191 women (88 standard surgery group, 103 lymphadenectomy group) had died, with a hazard ratio (HR) of 1.16 (95% CI 0.87-1.54; p=0.31) in favour of standard surgery and an absolute difference in 5-year overall survival of 1% (95% CI -4 to 6). 251 women died or had recurrent disease (107 standard surgery group, 144 lymphadenectomy group), with an HR of 1.35 (1.06-1.73; p=0.017) in favour of standard surgery and an absolute difference in 5-year recurrence-free survival of 6% (1-12). With adjustment for baseline characteristics and pathology details, the HR for overall survival was 1.04 (0.74-1.45; p=0.83) and for recurrence-free survival was 1.25 (0.93-1.66; p=0.14). Our results show no evidence of benefit in terms of overall or recurrence-free survival for pelvic lymphadenectomy in women with early
Ricciardi, E; Maniglio, P; Frega, A; Marci, R; Caserta, D; Moscarini, M
2012-12-01
Early-stage endometrial cancer and complex atypical hyperplasia are treated with hysterectomy and bilateral salpingo-oophorectomy. An emerging issue among younger women affected is the possibility of a fertility-sparing treatment with progestative therapy and close follow-up. To assess the possibility of conceiving after a diagnosis of atypical endometrial hyperplasia among women younger than 40 years old, in term of delaying definitive treatment and achieving pregnancy. 15 women younger than 40 years old with complex CAH or early carcinoma of the endometrium and a wish to preserve fertility. Progestins were administered orally for at least a 12 weeks period. Endometrial biopsies were used at follow-up. In 11 women, a complete pathological remission of the disease was observed. 4 pregnancies were attained in 4 women. 3 showed progression and underwent definitive surgery at 18 months. 1 showed no response at 24 months and 3 cycles and was counseled to receive a hysterectomy. A conservative approach in patients younger than 40 years appears a valid option, and a progestative therapy trial should be attempted whether a valid consensus is attained. Considering the risk to find AEH at biopsies and eventually a carcinoma at hysterectomy (25% of cases) a careful management is strictly required.
Isolated port-site metastasis after laparoscopic surgery for endometrial cancer: A case report
Palomba, Stefano; Falbo, Angela; Oppedisano, Rosamaria; Russo, Tiziana; Zullo, Fulvio
2012-01-01
► Isolated port-site metastasis is a rare event after laparoscopy in the surgical staging of endometrial cancer. ► More aggressive strategies in case of potentially increased risk for port-site metastasis are needed.
Endometriosis and risks for ovarian, endometrial and breast cancers
DEFF Research Database (Denmark)
Mogensen, Julie Brøchner; Kjær, Susanne K.; Mellemkjær, Lene
2016-01-01
Objective A growing body of evidence suggests that endometriosis increases the risk for ovarian cancer, but it is less well studied whether the excess risk is confined to certain histotypes. Furthermore, it is not fully resolved if endometriosis is associated with endometrial- and breast cancer....... The aim was to study overall- and histotype-specific risks for these hormone-dependent cancers in women with endometriosis. Methods In the Danish National Patient Register, we identified 45,790 women with a clinical diagnosis of endometriosis during 1977–2012. We linked the cohort to the Danish Cancer...... Register and calculated standardized incidence ratios (SIRs) with corresponding 95% confidence intervals (CIs). Results Endometriosis was associated with increased risks for ovarian cancer (SIR 1.34; 95% CI: 1.16–1.55), due primarily to endometrioid (SIR 1.64; 95% CI: 1.09–2.37) and clear-cell types (SIR 3...
Directory of Open Access Journals (Sweden)
Chelsea Zhang
2015-08-01
Conclusion: In this retrospective cohort analysis, Lumbee Native American ancestry was not a significant independent predictor of rates of high-risk histological subtypes of endometrial cancer or poor survival outcomes.
The risk of extra-colonic, extra-endometrial cancer in the Lynch syndrome
DEFF Research Database (Denmark)
Watson, Patrice; Vasen, Hans F A; Mecklin, Jukka-Pekka
2008-01-01
persons missing crucial information, cohort included 6,041 members of 261 families with LS-associated MLH1 or MSH2 mutations. All were either mutation carriers by test, probable mutation carriers (endometrial/colorectal cancer-affected), or first-degree relatives of these. Among mutation carriers...
Gee, Michael S; Atri, Mostafa; Bandos, Andriy I; Mannel, Robert S; Gold, Michael A; Lee, Susanna I
2018-04-01
Purpose To assess the accuracy of staging positron emission tomography (PET)/computed tomography (CT) in detecting distant metastasis in patients with local-regionally advanced cervical and high-risk endometrial cancer in the clinical trial by the American College of Radiology Imaging Network (ACRIN) and the Gynecology Oncology Group (GOG) (ACRIN 6671/GOG 0233) and to compare central and institutional reader performance. Materials and Methods In this prospective multicenter trial, PET/CT and clinical data were reviewed for patients enrolled in ACRIN 6671/GOG 0233. Two central readers, blinded to site read and reference standard, reviewed PET/CT images for distant metastasis. Central review was then compared with institutional point-of-care interpretation. Reference standard was pathologic and imaging follow-up. Test performance for central and site reviews of PET/CT images was calculated and receiver operating characteristic analysis was performed. Generalized estimating equations and nonparametric bootstrap procedure for clustered data were used to assess statistical significance. Results There were 153 patients with cervical cancer and 203 patients with endometrial cancer enrolled at 28 sites. Overall prevalence of distant metastasis was 13.7% (21 of 153) for cervical cancer and 11.8% (24 of 203) for endometrial cancer. Central reader PET/CT interpretation demonstrated sensitivity, specificity, positive predictive value (PPV), and negative predictive value of 54.8%, 97.7%, 79.3%, and 93.1% for cervical cancer metastasis versus 64.6%, 98.6%, 86.1%, and 95.4% for endometrial cancer, respectively. By comparison, local institutional review demonstrated sensitivity, specificity, PPV, and negative predictive value of 47.6%, 93.9%, 55.6%, and 91.9% for cervical cancer metastasis and 66.7%, 93.9%, 59.3%, and 95.5% for endometrial cancer, respectively. For central readers, the specificity and PPV of PET/CT detection of cervical and endometrial cancer metastases were all
Bredholt, Geir; Mannelqvist, Monica; Stefansson, Ingunn M; Birkeland, Even; Bø, Trond Hellem; Øyan, Anne M; Trovik, Jone; Kalland, Karl-Henning; Jonassen, Inge; Salvesen, Helga B; Wik, Elisabeth; Akslen, Lars A
2015-11-24
Tumor necrosis is associated with aggressive features of endometrial cancer and poor prognosis. Here, we investigated gene expression patterns and potential treatment targets related to presence of tumor necrosis in primary endometrial cancer lesions. By DNA microarray analysis, expression of genes related to tumor necrosis reflected multiple tumor-microenvironment interactions like tissue hypoxia, angiogenesis and inflammation pathways. A tumor necrosis signature of 38 genes and a related patient cluster (Cluster I, 67% of the cases) were associated with features of aggressive tumors such as type II cancers, estrogen receptor negative tumors and vascular invasion. Further, the tumor necrosis signature was increased in tumor cells grown in hypoxic conditions in vitro. Multiple genes with increased expression are known to be activated by HIF1A and NF-kB. Our findings indicate that the presence of tumor necrosis within primary tumors is associated with hypoxia, angiogenesis and inflammation responses. HIF1A, NF-kB and PI3K/mTOR might be potential treatment targets in aggressive endometrial cancers with presence of tumor necrosis.
Vaginal brachytherapy alone is sufficient adjuvant treatment of surgical stage I endometrial cancer
International Nuclear Information System (INIS)
Solhjem, Matthew C.; Petersen, Ivy A.; Haddock, Michael G.
2005-01-01
Purpose To determine the efficacy and complications of adjuvant vaginal high-dose-rate brachytherapy alone for patients with Stage I endometrial cancer in whom complete surgical staging had been performed. Methods and Materials Between April 1998 and March 2004, 100 patients with Stage I endometrial cancer underwent surgical staging (total abdominal hysterectomy and bilateral salpingo-oophorectomy with pelvic ± paraaortic nodal sampling) and postoperative vaginal high-dose-rate brachytherapy at our institution. The total dose was 2100 cGy in three fractions. Results With a median follow-up of 23 months (range 2-62), no pelvic or vaginal recurrences developed. All patients underwent pelvic dissection, and 42% underwent paraaortic nodal dissection. A median of 29.5 pelvic nodes (range 1-67) was removed (84% had >10 pelvic nodes removed). Most patients (73%) had endometrioid (or unspecified) adenocarcinoma, 16% had papillary serous carcinoma, and 11% had other histologic types. The International Federation of Gynecology and Obstetrics stage and grade was Stage IA, grade III in 5; Stage IB, grade I, II, or III in 6, 27, or 20, respectively; and Stage IC, grade I, II, or III in 13, 17, or 10, respectively. The Common Toxicity Criteria (version 2.0) complications were mild (Grade 1-2) and consisted primarily of vaginal mucosal changes, temporary urinary irritation, and temporary diarrhea. Conclusion Adjuvant vaginal high-dose-rate brachytherapy alone may be a safe and effective alternative to pelvic external beam radiotherapy for surgical Stage I endometrial cancer
Sleep quality of endometrial cancer survivors and the effect of treatments
Directory of Open Access Journals (Sweden)
Tolgay Tuyan İlhan
2017-12-01
Full Text Available Objective Sleep disorders affect 54.9% of gynaecologic cancer survivors. The effect of treatment methods on sleep quality is not clear. This study evaluated the sleep quality of survivors of endometrial cancer and compared the effects of different treatments on sleep quality. Materials and Methods Patients were categorised as surgery (group 1, surgery + brachytherapy (BRT (group 2, surgery + external beam radiation therapy (EBRT (group 3, and surgery + EBRT + BRT + chemotherapy (group 4. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI questionnaire. The PSQI was completed by the participants before surgery, 1, 3, and 6 months after each treatment was completed. The PSQI scores were compared between the different measurement times and different study groups. Results This study enrolled 114 patients with a mean age of 58.1±11 years. The number of participants in each group was 53 (46.5%, 14 (12.3%, 12 (10.5%, and 35 (30.7%, respectively. At baseline, 28 (24.6% patients reported poor sleep quality. The mean PSQI score reached the maximum level at the second measurement and decreased slightly during follow-up and the change in the PSQI score was significant (p=0.001. Group 3 and group 4 had significantly higher scores from baseline (p<0.008. At time point 3, the differences between the groups were significant. At time point 4, the most prominent effect of treatment on sleep quality was observed in patients with combined chemo-radiotherapy when compared with the other study groups. Conclusion Most survivors of endometrial cancer are affected by poor sleep quality during their treatment. To improve these patients’ quality of life, this disorder must be considered at each visit and tailored care plans should be developed to meet the women’s needs. Further studies are needed to evaluate the long-term results of sleep quality on patients with endometrial cancer.
Clinical Utility of Preoperative Computed Tomography in Patients With Endometrial Cancer.
Bogani, Giorgio; Gostout, Bobbie S; Dowdy, Sean C; Multinu, Francesco; Casarin, Jvan; Cliby, William A; Frigerio, Luigi; Kim, Bohyun; Weaver, Amy L; Glaser, Gretchen E; Mariani, Andrea
2017-10-01
The aim of this study was to determine the clinical utility of routine preoperative pelvic and abdominal computed tomography (CT) examinations in patients with endometrial cancer (EC). We retrospectively reviewed records from patients with EC who underwent a preoperative endometrial biopsy and had surgery at our institution from January 1999 through December 2008. In the subset with an abdominal CT scan obtained within 3 months before surgery, we evaluated the clinical utility of the CT scan. Overall, 224 patients (18%) had a preoperative endometrial biopsy and an available CT scan. Gross intra-abdominal disease was observed in 10% and 20% of patients with preoperative diagnosis of endometrioid G3 and type II EC, respectively, whereas less than 5% of patients had a preoperative diagnosis of hyperplasia or low-grade EC. When examining retroperitoneal findings, we observed that a negative CT scan of the pelvis did not exclude the presence of pelvic node metastasis. Alternately, a negative CT scan in the para-aortic area generally reduced the probability of finding para-aortic dissemination but with an overall low sensitivity (42%). However, the sensitivity for para-aortic dissemination was as high as 67% in patients with G3 endometrioid cancer. In the case of negative para-aortic nodes in the CT scan, the risk of para-aortic node metastases decreased from 18.8% to 7.5% in patients with endometrioid G3 EC. Up to 15% of patients with endometrioid G3 cancer had clinically relevant incidental findings that necessitated medical or surgical intervention. In patients with endometrioid G3 and type II EC diagnosed by the preoperative biopsy, CT scans may help guide the operative plan by facilitating preoperative identification of gross intra-abdominal disease and enlarged positive para-aortic nodes that are not detectable during physical examinations. In addition, CT may reveal other clinically relevant incidental findings.
Estrogen sulfotransferases in breast and endometrial cancers.
Pasqualini, Jorge Raul
2009-02-01
Estrogen sulfotransferase is significantly more active in the normal breast cell (e.g., Human 7) than in the cancer cell (e.g., MCF-7). The data suggest that in breast cancer sulfoconjugated activity is carried out by another enzyme, the SULT1A, which acts at high concentration of the substrates. In breast cancer cells sulfotransferase (SULT) activity can be stimulated by various progestins: medrogestone, promegestone, and nomegestrol acetate, as well as by tibolone and its metabolites. SULT activities can also be controlled by other substances including phytoestrogens, celecoxib, flavonoids (e.g., quercetin, resveratrol), and isoflavones. SULT expression was localized in breast cancer cells, which can be stimulated by promegestone and correlated with the increase of the enzyme activity. The estrogen sulfotransferase (SULT1E1), which acts at nanomolar concentration of estradiol, can inactivate most of this hormone present in the normal breast; however, in the breast cancer cells, the sulfotransferase denoted as SULT1A1 is mainly present, and this acts at micromolar concentrations of E(2). A correlation was postulated among breast cancer cell proliferation, the effect of various progestins, and sulfotransferase stimulation. In conclusion, it is suggested that factors involved in the stimulation of the estrogen sulfotransferases could provide new possibilities for the treatment of patients with hormone-dependent breast and endometrial cancers.
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Buchanan DD
2014-10-01
Full Text Available Daniel D Buchanan,1,2 Christophe Rosty,1,3,4 Mark Clendenning,1 Amanda B Spurdle,5 Aung Ko Win2 1Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, VIC, Australia; 2Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, VIC, Australia; 3Envoi Specialist Pathologists, Herston, QLD, Australia; 4School of Medicine, University of Queensland, Herston, QLD, Australia; 5Molecular Cancer Epidemiology Laboratory, Genetics and Computational Biology Division, QIMR Berghofer Medical Research Institute, Herston, QLD, AustraliaAbstract: Carriers of a germline mutation in one of the DNA mismatch repair (MMR genes have a high risk of developing numerous different cancers, predominantly colorectal cancer and endometrial cancer (known as Lynch syndrome. MMR gene mutation carriers develop tumors with MMR deficiency identified by tumor microsatellite instability or immunohistochemical loss of MMR protein expression. Tumor MMR deficiency is used to identify individuals most likely to carry an MMR gene mutation. However, MMR deficiency can also result from somatic inactivation, most commonly methylation of the MLH1 gene promoter. As tumor MMR testing of all incident colorectal and endometrial cancers (universal screening is becoming increasingly adopted, a growing clinical problem is emerging for individuals who have tumors that show MMR deficiency who are subsequently found not to carry an MMR gene mutation after genetic testing using the current diagnostic approaches (Sanger sequencing and multiplex ligation-dependent probe amplification and who also show no evidence of MLH1 methylation. The inability to determine the underlying cause of tumor MMR deficiency in these "Lynch-like" or "suspected Lynch syndrome" cases has significant implications on the clinical management of these individuals and their relatives. When the
Safety of laparoscopy versus laparotomy in early-stage endometrial cancer : a randomised trial
Mourits, M.J.E.; Bijen, C.B.; Arts, H.J.; Ter Brugge, H.G.; van der Sijde, R.; Paulsen, L.; Wijma, J.; Bongers, M.Y.; Post, W.J.; van der Zee, A.G.; de Bock, G.H.
Background The standard surgery for early-stage endometrial cancer is total abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy, which is associated with substantial morbidity. Total laparoscopic hysterectomy (TLH) and bilateral salpingo-oophorectomy is less invasive and is assumed to
Bolton, Katherine A; Holliday, Elizabeth G; Attia, John; Bowden, Nikola A; Avery-Kiejda, Kelly A; Scott, Rodney J
2016-05-26
The estrogen-induced gene 121 (EIG121) has been associated with breast and endometrial cancers, but its mechanism of action remains unknown. In a genome-wide search for tandem repeats, we found that EIG121 contains a short tandem repeat (STR) in its upstream regulatory region which has the potential to alter gene expression. The presence of this STR has not previously been analysed in relation to breast or endometrial cancer risk. In this study, the lengths of this STR were determined by PCR, fragment analysis and sequencing using DNA from 223 breast cancer patients, 204 endometrial cancer patients and 220 healthy controls to determine if they were associated with the risk of developing breast or endometrial cancer. We found this repeat to be highly variable with the number of copies of the AG motif ranging from 27 to 72 and having a bimodal distribution. No statistically significant association was identified between the length of this STR and the risk of developing breast or endometrial cancer or age at diagnosis. The STR in the upstream regulatory region of EIG121 is highly polymorphic, but is not associated with the risk of developing breast or endometrial cancer in the cohorts analysed here. While this polymorphic STR in the regulatory region of EIG121 appears to have no impact on the risk of developing breast or endometrial cancer, its association with disease recurrence or overall survival remains to be determined.
Bantysh, B B; Paukov, v S; Kogan, E A
2012-01-01
The results of a immunomorphologic comprehensive study of epithelial-stromal relationships in the uterus hyperplasia and endometrial cancer suggest that the suppressor gene of cancer (PTEN) plays a key role in the process of neoplastic transformation of endometrial hyperplasia and adenocarcinoma development. For the first time the existence of two highly differentiated endometrial adenocarcinoma immunophenotype were detected The first one is a PTEN-negative endometrial aedenocarcinoma, characterized by an almost complete inhibition of tumor suppressor gene PTEN in the epithelium of the glands and stromal cell of the tumor The second type is a PTEN-positive endometrial adenocarcinoma, in which epithelial and stromal tumor suppressor gene PTEN activity has retained Based on these results we have formulated a hypothesis about the different types of endometrial hyperplasia morphogenesis and its possible transfer to cervical cancer associated with features of tumor suppressor gene PTEN.
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Pinilla, James
1998-01-01
Purpose: Endometrial cancer is a common, usually curable malignancy whose treatment frequently involves low-dose-rate (LDR) or high-dose-rate (HDR) brachytherapy. These treatments involve substantial resource commitments and this is increasingly important. This paper presents a cost minimization analysis of HDR versus LDR brachytherapy in the treatment of endometrial cancer. Methods and Materials: The perspective of the analysis is that of the payor, in this case the Ministry of Health. One course of LDR treatment is compared to two courses of HDR treatment. The two alternatives are considered to be comparable with respect to local control, survival, and toxicities. Labor, overhead, and capital costs are accounted for and carefully measured. A 5% inflation rate is used where applicable. A univariate sensitivity analysis is performed. Results: The HDR regime is 22% less expensive compared to the LDR regime. This is $991.66 per patient or, based on the current workload of this department (30 patients per year) over the useful lifetime of the after loader, $297,498 over 10 years in 1997 dollars. Conclusion: HDR brachytherapy minimizes costs in the treatment of endometrial cancer relative to LDR brachytherapy. These results may be used by other centers to make rational decisions regarding brachytherapy equipment replacement or acquisition
Dong, Ruofan; Pu, Hong; Wang, Yuan; Yu, Jinjin; Lian, Kuixian; Mao, Caiping
2015-05-01
We previously reported frequent loss of TESTIN in human endometrial carcinoma, which significantly suppressed tumor proliferation and invasion. Herein, we further explored the mechanisms underlying TESTIN loss and its roles in the epithelial-mesenchymal transition (EMT, a key step for tumor spreading). Methylation-specific PCR was performed to investigate the promoter status of TESTIN in a panel of endometrial cancer and normal endometrium tissues. The expression of TESTIN mRNA was determined by real-time PCR. Up- and down-regulation of TESTIN were achieved by transient transfection with pcDNA3.1-TESTIN and shRNA-TESTIN plasmids, respectively. The EMT alterations were observed under the optical microscope and EMT-related markers were detected by real-time PCR and western blot. Compared to the control (3.6%), TESTIN was hypermethylated in 43.7% endometrial cancer tissues (p < 0.001). Moreover, TESTIN hypermethylation was significantly correlated with advanced tumor stage, deep myometrial invasion and lymphatic node metastasis. In vitro, the demethylating agent dramatically restored the expression of TESTIN. In addition, up-regulation of TESTIN significantly suppressed the EMT procedure; whereas down-regulation of TESTIN enhanced EMT. In conclusion, we demonstrated that loss of TESTIN was mainly caused by hypermethylation, which might be a potent prognostic marker. Furthermore, we proved that TESTIN significantly suppressed the EMT procedure, proposing restoration of TESTIN to be a novel therapeutic strategy for endometrial carcinoma. © 2015 APMIS. Published by John Wiley & Sons Ltd.
van Hanegem, Nehalennia; Prins, Marileen M C; Bongers, Marlies Y; Opmeer, Brent C; Sahota, Daljit Singh; Mol, Ben Willem J; Timmermans, Anne
2016-02-01
Postmenopausal bleeding (PMB) can be the first sign of endometrial cancer. In case of thickened endometrium, endometrial sampling is often used in these women. In this systematic review, we studied the accuracy of endometrial sampling for the diagnoses of endometrial cancer, atypical hyperplasia and endometrial disease (endometrial pathology, including benign polyps). We systematically searched the literature for studies comparing the results of endometrial sampling in women with postmenopausal bleeding with two different reference standards: blind dilatation and curettage (D&C) and hysteroscopy with histology. We assessed the quality of the detected studies by the QUADAS-2 tool. For each included study, we calculated the fraction of women in whom endometrial sampling failed. Furthermore, we extracted numbers of cases of endometrial cancer, atypical hyperplasia and endometrial disease that were identified or missed by endometrial sampling. We detected 12 studies reporting on 1029 women with postmenopausal bleeding: five studies with dilatation and curettage (D&C) and seven studies with hysteroscopy as a reference test. The weighted sensitivity of endometrial sampling with D&C as a reference for the diagnosis of endometrial cancer was 100% (range 100-100%) and 92% (71-100) for the diagnosis of atypical hyperplasia. Only one study reported sensitivity for endometrial disease, which was 76%. When hysteroscopy was used as a reference, weighted sensitivities of endometrial sampling were 90% (range 50-100), 82% (range 56-94) and 39% (21-69) for the diagnosis of endometrial cancer, atypical hyperplasia and endometrial disease, respectively. For all diagnosis studied and the reference test used, specificity was 98-100%. The weighted failure rate of endometrial sampling was 11% (range 1-53%), while insufficient samples were found in 31% (range 7-76%). In these women with insufficient or failed samples, an endometrial (pre) cancer was found in 7% (range 0-18%). In women with
Goebel, Emily A; Vidal, August; Matias-Guiu, Xavier; Blake Gilks, C
2017-12-12
Uterine cancer was first subclassified based on anatomic site, separating those tumours arising from the endometrium from cervical cancers. There was then further subclassification of endometrial cancers based on cell type, and this correlated with the Type I and Type II categories identified through the epidemiological studies of Bokhman, with endometrioid carcinoma corresponding (approximately) to Type I and serous carcinoma to Type II. These histotypes are not clearly separable in practice, however, with considerable interobserver variability in histotype diagnosis, especially for high-grade tumours. There followed studies of immunomarkers and then mutational studies of single genes, in attempts to improve subclassification. While these have revealed significant differences in protein expression and mutation profiles between endometrioid and serous carcinomas, there is also considerable overlap, so that there remain challenges in subclassification of endometrial carcinoma. Gene panel testing, using next-generation sequencing, was applied to endometrial cancers and highlighted that there are tumours that show genetic alterations intermediate between classic Type I/endometrioid and Type II/serous carcinomas. The Cancer Genome Atlas studies of endometrioid and serous carcinoma offered revolutionary insight into the subclassification of endometrial carcinoma, i.e. that there are four distinct categories of endometrial carcinoma, rather than two, based on genomic architecture. In this review, we provide an overview of immunohistochemical and molecular markers in endometrial carcinoma and comment on the important future directions in endometrial carcinoma subclassification arising from The Cancer Genome Atlas results.
The relationship of local and distant failure from endometrial cancer: defining a clinical paradigm
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Corn, Benjamin W.; Lanciano, Rachelle; D'Agostino, Ralph; Kiggundu, Edward; Purser, Phillip; Greven, Kathryn M.
1996-01-01
PURPOSE: The Gynecologic Oncology Group (GOG) has recently activated a phase III protocol (no. 156) that randomizes women with intermediate risk endometrial cancer to pelvic irradiation (RT) vs. chemotherapy (cisplatin, doxorubicin). This study design presumes that chemotherapy will be able to control local disease, or that local disease is a minimal problem and that distant metastases arise independent of local failure. Recently, statistical methods have been developed to rigorously assess the relationship between local and distant failures. Such methodology has successfully been applied to a variety of tumors including those arising in the prostate, breast, and cervix. To date, no published data are available to generate an hypothesis to characterize the relationship between local and distant failure for endometrial cancer. The present analysis was undertaken to determine the effect of loco-regional control on subsequent metastatic dissemination among women with pathologically staged endometrial cancer treated by hysterectomy followed by adjuvant radiotherapy. METHODS: The series consisted of 394 patients with FIGO stages I-IVa endometrial cancer who were surgically staged prior to irradiation [median external beam dose 46 Gy +/- brachytherapy (median vaginal surface dose=30 Gy)]. The duration of follow-up ranged from 2 to 80 months, with a median of 50 months. Multiple factors were evaluated to determine the associations with distant relapse including FIGO pathological stage, grade, histopathologic subtype (adeno, vs papillary/papillary-serous/clear cell), depth of myometrial penetration, age, and local disease status. Time dependent survival models were generated to assess the influence of local failure on distant metastases. RESULTS: For the entire series, the 5 year actuarial rates of local and distant failures were 9% and 20%, respectively. Women who failed locally had a >6-fold risk of failing distantly compared to those who remained locally controlled (p=0
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Cymbaluk-Płoska A
2018-03-01
Full Text Available Aneta Cymbaluk-Płoska,1 Anita Chudecka-Głaz,1 Anna Jagodzińska,1 Ewa Pius-Sadowska,2 Agnieszka Sompolska-Rzechuła,3 Bogusław Machaliński,2 Janusz Menkiszak1 1Department of Gynecological Surgery and Gynecological Oncology of Adults and Adolescents, Pomeranian Medical University, Szczecin, Poland; 2General Pathology Department, Pomeranian Medical University, Szczecin, Poland; 3Department of Statistics, West Pomeranian University of Technology, Szczecin, Poland Introduction: Adipose tissue is considered an endocrine organ and produces a number of biologically active substances. Aims: To consider the role that four adipokines – leptin, omentin-1, vaspin, and galectin-3 – play in the diagnosis of endometrium cancer and to investigate the association between serum concentrations of adipose tissue metabolism products and the diagnostics and prognosis in endometrial cancer. Patients and methods: The study included 168 patients with body mass index (BMI >20 kg/m2 admitted due to post-menopausal bleeding. Results: A receiver operating characteristic curves test was performed to determine the diagnostic values of the proteins tested. For leptin and galectin-3 the area under the curve (AUC values were 0.79/0.68, while for vaspin and omentin-1 the AUC values were 0.82/0.86 for all study patients. The final model identified the following independent risk factors: glucose concentration, BMI, waist circumference, leptin, and vaspin concentrations. Diagnostic values of leptin and galectin-3 with regard to differentiation between high (Fédération Internationale de Gynécologie Obstétrique [FIGO] III and IV and low (FIGO I and II stages of clinical tumor advancement and prediction of tumor grading (G1 vs G3 based on the AUC curve were 0.82/0.70 and 0.80/0.74. The AUC values for vaspin and omentin-1 with respect to differentiation between histopathological advancement and grading were 0.86/0.81 and 0.83/0.77, respectively. Significantly lower values of
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Ballester Marcos
2010-08-01
Full Text Available Abstract Background Lymphadenectomy is debated in early stages endometrial cancer. Moreover, a new FIGO classification of endometrial cancer, merging stages IA and IB has been recently published. Therefore, the aims of the present study was to evaluate the relevance of the sentinel node (SN procedure in women with endometrial cancer and to discuss whether the use of the 2009 FIGO classification could modify the indications for SN procedure. Methods Eighty-five patients with endometrial cancer underwent the SN procedure followed by pelvic lymphadenectomy. SNs were detected with a dual or single labelling method in 74 and 11 cases, respectively. All SNs were analysed by both H&E staining and immunohistochemistry. Presumed stage before surgery was assessed for all patients based on MR imaging features using the 1988 FIGO classification and the 2009 FIGO classification. Results An SN was detected in 88.2% of cases (75/85 women. Among the fourteen patients with lymph node metastases one-half were detected by serial sectioning and immunohistochemical analysis. There were no false negative case. Using the 1988 FIGO classification and the 2009 FIGO classification, the correlation between preoperative MRI staging and final histology was moderate with Kappa = 0.24 and Kappa = 0.45, respectively. None of the patients with grade 1 endometrioid carcinoma on biopsy and IA 2009 FIGO stage on MR imaging exhibited positive SN. In patients with grade 2-3 endometrioid carcinoma and stage IA on MR imaging, the rate of positive SN reached 16.6% with an incidence of micrometastases of 50%. Conclusions The present study suggests that sentinel node biopsy is an adequate technique to evaluate lymph node status. The use of the 2009 FIGO classification increases the accuracy of MR imaging to stage patients with early stages of endometrial cancer and contributes to clarify the indication of SN biopsy according to tumour grade and histological type.
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Ballester, Marcos; Koskas, Martin; Coutant, Charles; Chéreau, Elisabeth; Seror, Jeremy; Rouzier, Roman; Daraï, Emile
2010-01-01
Lymphadenectomy is debated in early stages endometrial cancer. Moreover, a new FIGO classification of endometrial cancer, merging stages IA and IB has been recently published. Therefore, the aims of the present study was to evaluate the relevance of the sentinel node (SN) procedure in women with endometrial cancer and to discuss whether the use of the 2009 FIGO classification could modify the indications for SN procedure. Eighty-five patients with endometrial cancer underwent the SN procedure followed by pelvic lymphadenectomy. SNs were detected with a dual or single labelling method in 74 and 11 cases, respectively. All SNs were analysed by both H&E staining and immunohistochemistry. Presumed stage before surgery was assessed for all patients based on MR imaging features using the 1988 FIGO classification and the 2009 FIGO classification. An SN was detected in 88.2% of cases (75/85 women). Among the fourteen patients with lymph node metastases one-half were detected by serial sectioning and immunohistochemical analysis. There were no false negative case. Using the 1988 FIGO classification and the 2009 FIGO classification, the correlation between preoperative MRI staging and final histology was moderate with Kappa = 0.24 and Kappa = 0.45, respectively. None of the patients with grade 1 endometrioid carcinoma on biopsy and IA 2009 FIGO stage on MR imaging exhibited positive SN. In patients with grade 2-3 endometrioid carcinoma and stage IA on MR imaging, the rate of positive SN reached 16.6% with an incidence of micrometastases of 50%. The present study suggests that sentinel node biopsy is an adequate technique to evaluate lymph node status. The use of the 2009 FIGO classification increases the accuracy of MR imaging to stage patients with early stages of endometrial cancer and contributes to clarify the indication of SN biopsy according to tumour grade and histological type
Broeders, F.M.; Wurff, A.A. van der; Pijnenborg, J.M.A.; Vos, M.C.
2012-01-01
OBJECTIVE: For treatment of patients with both endometrial and ovarian cancer, it is important to discriminate between 2 primary tumors and metastatic disease. Currently, criteria are based on postoperative findings. The aim of this study was to determine whether clinical parameters can discriminate
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Diaz-Valdivia, Natalia; Bravo, Denisse; Huerta, Hernán; Henriquez, Soledad; Gabler, Fernando; Vega, Margarita; Romero, Carmen; Calderon, Claudia; Owen, Gareth I.; Leyton, Lisette; Quest, Andrew F. G.
2015-01-01
Caveolin-1 (CAV1) has been implicated both in tumor suppression and progression, whereby the specific role appears to be context dependent. Endometrial cancer is one of the most common malignancies of the female genital tract; however, little is known about the role of CAV1 in this disease. Here, we first determined by immunohistochemistry CAV1 protein levels in normal proliferative human endometrium and endometrial tumor samples. Then using two endometrial cancer cell lines (ECC: Ishikawa and Hec-1A) we evaluated mRNA and protein levels of CAV1 by real time qPCR and Western blot analysis, respectively. The role of CAV1 expression in ECC malignancy was further studied by either inducing its expression in endometrial cancer cells with the tumor promotor 12-O-tetradecanoyl-phorbol-13-acetate (4β-TPA) or decreasing expression using short-hairpin RNA constructs, and then evaluating the effects of these changes on ECC proliferation, transmigration, matrigel invasion, and colony formation in soft agar. Immunohistochemical analysis of endometrial epithelia revealed that substantially higher levels of CAV1 were present in endometrial tumors than the normal proliferative epithelium. Also, in Ishikawa and Hec-1A endometrial cancer cells CAV1 expression was readily detectable. Upon treatment with 4β-TPA CAV1 levels increased and coincided with augmented cell transmigration, matrigel invasion, as well as colony formation in soft agar. Reduction of CAV1 expression using short-hairpin RNA constructs ablated these effects in both cell types whether treated or not with 4β-TPA. Alternatively, CAV1 expression appeared not to modulate significantly proliferation of these cells. Our study shows that elevated CAV1, observed in patients with endometrial cancer, is linked to enhanced malignancy of endometrial cancer cells, as evidenced by increased migration, invasion and anchorage-independent growth. The online version of this article (doi:10.1186/s12885-015-1477-5) contains
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Masakazu Kitagawa
2017-02-01
Conclusion: Total laparoscopic modified radical hysterectomy is safe and feasible for the treatment of early stage endometrial cancer. This procedure can be an alternative to total laparoscopic hysterectomy, especially when the uterus must be removed completely.
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Nyholm, H C; Nielsen, Anette Lynge; Norup, P
1993-01-01
Clinical and histopathological features of postmenopausal endometrial cancer were studied in 63 patients who had received exogenous estrogens previously and in 76 patients who had never been exposed to estrogens. All treatments were primarily surgical. Estrogen users were younger than nonusers (P...... metaplasia and "foam" cells were not related to tumor grade or use of estrogens. The receptor content correlated inversely with grade but was not related to estrogen use. Duration of estrogen treatment was not associated with tumor stage and grade. Our findings support the theory that endometrial cancer...
Markowska, Anna; Pawałowska, Monika; Filas, Violetta; Korski, Konstanty; Gryboś, Marian; Sajdak, Stefan; Olejek, Anita; Bednarek, Wiesława; Spiewankiewicz, Beata; Lubin, Jolanta; Markowska, Janina
2013-12-05
Diabetes mellitus, as a risk factor for endometrial cancer (EC), causes an increase in insulin and IGF-1 concentrations in the blood serum. The increase in insulin and IGF-1 are considered mitogenic factors contributory to cancer development. Studies suggest that metformin has preventive activity, decreasing mortality and the risk of neoplasms. Since estrogen (ER), progesterone (PR) and IGF-1 (IGF-1R) receptor expression and β-catenin and PAX-2 mutations are significant in the development of endometrial cancer, it was decided to study these factors in patients with endometrial cancer and type 2 diabetes mellitus (DM2), and to establish the effects of metformin on their expression. The expression of ER, PR, IGF-1R, β-catenin and PAX-2 have been immunohistochemically investigated in 86 type I endometrial cancer specimens. Patients were grouped according to the presence of DM2 and the type of hypoglycemic treatment administered. Comparing EC patients with DM2 and normal glycemic status, we found increased IGF-1R expression in women with DM2. A decrease in ER expression was noted in women with EC and DM2 receiving metformin as compared to women treated with insulin (p = 0.004). There was no statistically significant difference in PR, IGF-1R, β-catenin and PAX-2 expression among women receiving metformin and other hypoglycemic treatment. Although epidemiological studies suggest the beneficial role of metformin in many human cancers, there are still few studies confirming its favorable effect on endometrial cancer. Decreased ER expression in patients receiving metformin needs further research to allow evaluation of its clinical significance.
A Common Variant at the 14q32 Endometrial Cancer Risk Locus Activates AKT1 through YY1 Binding
Painter, Jodie N.; Kaufmann, Susanne; O’Mara, Tracy A.; Hillman, Kristine M.; Sivakumaran, Haran; Darabi, Hatef; Cheng, Timothy H.T.; Pearson, John; Kazakoff, Stephen; Waddell, Nicola; Hoivik, Erling A.; Goode, Ellen L.; Scott, Rodney J.; Tomlinson, Ian; Dunning, Alison M.
2016-01-01
A recent meta-analysis of multiple genome-wide association and follow-up endometrial cancer case-control datasets identified a novel genetic risk locus for this disease at chromosome 14q32.33. To prioritize the functional SNP(s) and target gene(s) at this locus we employed an in silico fine-mapping approach using genotyped and imputed SNP data for 6,608 endometrial cancer cases and 37,925 controls of European ancestry. Association and functional analyses provide evidence that the best candida...
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Cantinha, Rebeca S.; Santos, Mariana L.O.; Franca, Elvis J.; Pessoa, Juanna G.; Melo, Ana M.M.A.; Amancio, Francisco F.
2014-01-01
Cancer is a worldwide public health problem, its prevention and control are included within 16 strategic objectives of the Brazilian Ministry of Health for the period 2011-2015. Cervical cancer is the fourth most common tumor in the female population, being new 15,590 cases estimated for 2014 according to the Brazilian National Cancer Institute (INCA). Pernambuco is the fifth state with the highest number of cases of cervical cancer and the seventh in cases of endometrial ones, both estimative for 2014. The understanding of the epidemiological profile of these pathologies corroborates strategies for prevention, control and treatment. As Pernambuco has implemented the radiotherapy for cancer treatment since 1998-1999, this work encompassed the comparison of the 1998-1999 epidemiological profile of patients treated by radiotherapy for cervical and endometrial cancer in the State of Pernambuco, Brazil, with 2008-2009 profile - ten years after. Medical record of 490 patients treated at the Center of Radiotherapy of Pernambuco (CERAPE) were compiled according to the patient origin, the affected uterus region, the staging of disease, the type and cell differentiation of the tumor, the age group, and, finally, the realization of hysterectomy as part of the treatment. More than 90% of the patients were affected by cervical cancer in the two investigated periods. For the interval of 1998-1999 the proportion of patients submitted to hysterectomy was quite higher compared to those after ten years. The results also showed a change in the origin of the patients, in which, in 1999, most of the patients were from the capital and the metropolitan area, while, after ten years, patients were mostly from the interior of the State. There was a predominance of squamous cell type tumors in both periods evaluated. For the 1998-1999 interval, tumors were stage 2, moderately differentiated type. Differently, the tumors were mostly stage 3, not differentiated type, for the 2008-2009 period
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Cantinha, Rebeca S.; Santos, Mariana L.O.; Franca, Elvis J., E-mail: ejfranca@yahoo.com.br, E-mail: marianasantos_ufpe@hotmail.com, E-mail: rebecanuclear@gmail.com [Centro Regional de Ciencias Nucleares do Nordeste (CRCN-NE/CNEN-PE), Recife, PE (Brazil); Pessoa, Juanna G.; Melo, Ana M.M.A.; Amancio, Francisco F., E-mail: amdemelo@hotmail.com, E-mail: amanciobike@gmail.com, E-mail: juannapessoa@gmail.com, E-mail: marianasantos_ufpe@hotmail.com [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil). Departamento de Biofisica e Radiobiologia; Oliveira Neto, Aristides M.; Melo, Jonathan A., E-mail: aristidesoliveira466@hotmail.com, E-mail: jonathan@truenet.com.br [Centro de Radioterapia de Pernambuco (CERAPE), Santo Amaro, PE (Brazil)
2014-07-01
Cancer is a worldwide public health problem, its prevention and control are included within 16 strategic objectives of the Brazilian Ministry of Health for the period 2011-2015. Cervical cancer is the fourth most common tumor in the female population, being new 15,590 cases estimated for 2014 according to the Brazilian National Cancer Institute (INCA). Pernambuco is the fifth state with the highest number of cases of cervical cancer and the seventh in cases of endometrial ones, both estimative for 2014. The understanding of the epidemiological profile of these pathologies corroborates strategies for prevention, control and treatment. As Pernambuco has implemented the radiotherapy for cancer treatment since 1998-1999, this work encompassed the comparison of the 1998-1999 epidemiological profile of patients treated by radiotherapy for cervical and endometrial cancer in the State of Pernambuco, Brazil, with 2008-2009 profile - ten years after. Medical record of 490 patients treated at the Center of Radiotherapy of Pernambuco (CERAPE) were compiled according to the patient origin, the affected uterus region, the staging of disease, the type and cell differentiation of the tumor, the age group, and, finally, the realization of hysterectomy as part of the treatment. More than 90% of the patients were affected by cervical cancer in the two investigated periods. For the interval of 1998-1999 the proportion of patients submitted to hysterectomy was quite higher compared to those after ten years. The results also showed a change in the origin of the patients, in which, in 1999, most of the patients were from the capital and the metropolitan area, while, after ten years, patients were mostly from the interior of the State. There was a predominance of squamous cell type tumors in both periods evaluated. For the 1998-1999 interval, tumors were stage 2, moderately differentiated type. Differently, the tumors were mostly stage 3, not differentiated type, for the 2008-2009 period
An inhibitor of K+ channels modulates human endometrial tumor-initiating cells
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Leslie Kimberly K
2011-08-01
Full Text Available Abstract Background Many potassium ion (K+ channels function as oncogenes to sustain growth of solid tumors, but their role in cancer progression is not well understood. Emerging evidence suggests that the early progenitor cancer cell subpopulation, termed tumor initiating cells (TIC, are critical to cancer progression. Results A non-selective antagonist of multiple types of K+ channels, tetraethylammonium (TEA, was found to suppress colony formation in endometrial cancer cells via inhibition of putative TIC. The data also indicated that withdrawal of TEA results in a significant enhancement of tumorigenesis. When the TIC-enriched subpopulation was isolated from the endometrial cancer cells, TEA was also found to inhibit growth in vitro. Conclusions These studies suggest that the activity of potassium channels significantly contributes to the progression of endometrial tumors, and the antagonists of potassium channels are candidate anti-cancer drugs to specifically target tumor initiating cells in endometrial cancer therapy.
Identification of HNPCC by Molecular Analysis of Colorectal and Endometrial Tumors
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H. F. A. Vasen
2004-01-01
Full Text Available Hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome is a dominantly inherited syndrome characterized by the development of colorectal cancer, endometrial cancer and other cancers and the presence of microsatellite instability (MSI in tumors. The Bethesda guidelines have been proposed for the identification of families suspected of HNPCC that require further molecular analysis. We have evaluated the yield of MSI-analysis in a large series of Dutch families suspected of HNPCC. We also analysed whether the loss of mismatch repair (MMR protein detected by immunohistochemistry (IHC of colorectal cancer (CRC and endometrial cancer correlated with the presence of MSI and/or a MMR gene mutation. The results showed that the Bethesda criteria with a few modifications are appropriate to identify families eligible for genetic testing. In addition, we found that MSI and IHC-analysis of CRC using antibodies against MLH1, MSH2, MSH6 and PMS2 proteins are equally effective for identifying carriers of the known MMR gene defects. However, as long as the role of other putative MMR genes in hereditary CRC has not been elucidated, IHC-analysis cannot completely replace MSI. For this reason, we prefer MSI-analysis as first step in families suspected of HNPCC. On the other hand, in families fulfilling the revised Amsterdam criteria in which the probability of detecting a mutation is relatively high, we would recommend IHC as first diagnostic step because the result might predict the specific underlying MMR gene mutation. MSI or IHC-analysis of endometrial cancer alone was found to be less sensitive compared with these tests performed in colorectal cancer. Therefore, probably the best approach in the analysis of this cancer is to perform both techniques. The identification of HNPCC is important as it makes it possible to target effective preventative measures. Our studies showed that MSI and IHC analysis of colorectal and endometrial cancer, are reliable
Sirohi, Vijay Kumar; Popli, Pooja; Sankhwar, Pushplata; Kaushal, Jyoti Bala; Gupta, Kanchan; Manohar, Murli; Dwivedi, Anila
2017-06-01
Although curcumin shows anti-proliferative and anti-inflammatory activities in various cancers, the effect of curcumin on cellular migration in endometrial adenocarcinoma cells remains to be understood. The current investigation was aimed to explore the anti-proliferative and anti-migratory effects of curcumin and its mechanism of action in endometrial cancer cells. Our in-vitro and in-vivo experimental studies showed that curcumin inhibited the proliferation of endometrial cancer cells and suppressed the tumor growth in Ishikawa xenograft mouse model. Curcumin induced ROS-mediated apoptosis in endometrial cancer cells. Curcumin suppressed the migration rate of Ishikawa and Hec-1B cells as analyzed by scratch wound assay. In transwell migration studies, knock down of Slit-2 reversed the anti-migratory effect of curcumin in these cell lines. Curcumin significantly up-regulated the expression of Slit-2 in Ishikawa, Hec-1B and primary endometrial cancer cells while it down-regulated the expression of stromal cell-derived factor-1 (SDF-1) and CXCR4 which in turn, suppressed the expression of matrix metallopeptidases (MMP) 2 and 9, thus attenuating the migration of endometrial cancer cells. In summary, we have demonstrated that curcumin has inhibitory effect on cellular migration via Slit-2 mediated down-regulation of CXCR4, SDF-1, and MMP2/MMP9 in endometrial carcinoma cells. These findings helped explore the role of Slit-2 in endometrial cancer cells. Copyright © 2017 Elsevier Inc. All rights reserved.
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Young, Amy V.; Wortham, Angela; Wernick, Iddo; Evans, Andrew; Ennis, Ronald D.
2011-01-01
Purpose: Accurate target delineation of the nodal volumes is essential for three-dimensional conformal and intensity-modulated radiotherapy planning for endometrial cancer adjuvant therapy. We hypothesized that atlas-based segmentation ('autocontouring') would lead to time savings and more consistent contours among physicians. Methods and Materials: A reference anatomy atlas was constructed using the data from 15 postoperative endometrial cancer patients by contouring the pelvic nodal clinical target volume on the simulation computed tomography scan according to the Radiation Therapy Oncology Group 0418 trial using commercially available software. On the simulation computed tomography scans from 10 additional endometrial cancer patients, the nodal clinical target volume autocontours were generated. Three radiation oncologists corrected the autocontours and delineated the manual nodal contours under timed conditions while unaware of the other contours. The time difference was determined, and the overlap of the contours was calculated using Dice's coefficient. Results: For all physicians, manual contouring of the pelvic nodal target volumes and editing the autocontours required a mean ± standard deviation of 32 ± 9 vs. 23 ± 7 minutes, respectively (p = .000001), a 26% time savings. For each physician, the time required to delineate the manual contours vs. correcting the autocontours was 30 ± 3 vs. 21 ± 5 min (p = .003), 39 ± 12 vs. 30 ± 5 min (p = .055), and 29 ± 5 vs. 20 ± 5 min (p = .0002). The mean overlap increased from manual contouring (0.77) to correcting the autocontours (0.79; p = .038). Conclusion: The results of our study have shown that autocontouring leads to increased consistency and time savings when contouring the nodal target volumes for adjuvant treatment of endometrial cancer, although the autocontours still required careful editing to ensure that the lymph nodes at risk of recurrence are properly included in the target volume.
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Ruth M Pfeiffer
Full Text Available Breast, endometrial, and ovarian cancers share some hormonal and epidemiologic risk factors. While several models predict absolute risk of breast cancer, there are few models for ovarian cancer in the general population, and none for endometrial cancer.Using data on white, non-Hispanic women aged 50+ y from two large population-based cohorts (the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial [PLCO] and the National Institutes of Health-AARP Diet and Health Study [NIH-AARP], we estimated relative and attributable risks and combined them with age-specific US-population incidence and competing mortality rates. All models included parity. The breast cancer model additionally included estrogen and progestin menopausal hormone therapy (MHT use, other MHT use, age at first live birth, menopausal status, age at menopause, family history of breast or ovarian cancer, benign breast disease/biopsies, alcohol consumption, and body mass index (BMI; the endometrial model included menopausal status, age at menopause, BMI, smoking, oral contraceptive use, MHT use, and an interaction term between BMI and MHT use; the ovarian model included oral contraceptive use, MHT use, and family history or breast or ovarian cancer. In independent validation data (Nurses' Health Study cohort the breast and ovarian cancer models were well calibrated; expected to observed cancer ratios were 1.00 (95% confidence interval [CI]: 0.96-1.04 for breast cancer and 1.08 (95% CI: 0.97-1.19 for ovarian cancer. The number of endometrial cancers was significantly overestimated, expected/observed = 1.20 (95% CI: 1.11-1.29. The areas under the receiver operating characteristic curves (AUCs; discriminatory power were 0.58 (95% CI: 0.57-0.59, 0.59 (95% CI: 0.56-0.63, and 0.68 (95% CI: 0.66-0.70 for the breast, ovarian, and endometrial models, respectively.These models predict absolute risks for breast, endometrial, and ovarian cancers from easily obtainable risk factors and may
Boretto, Matteo; Cox, Benoit; Noben, Manuel; Hendriks, Nikolai; Fassbender, Amelie; Roose, Heleen; Amant, Frédéric; Timmerman, Dirk; Tomassetti, Carla; Vanhie, Arne; Meuleman, Christel; Ferrante, Marc; Vankelecom, Hugo
2017-05-15
The endometrium, which is of crucial importance for reproduction, undergoes dynamic cyclic tissue remodeling. Knowledge of its molecular and cellular regulation is poor, primarily owing to a lack of study models. Here, we have established a novel and promising organoid model from both mouse and human endometrium. Dissociated endometrial tissue, embedded in Matrigel under WNT-activating conditions, swiftly formed organoid structures that showed long-term expansion capacity, and reproduced the molecular and histological phenotype of the tissue's epithelium. The supplemented WNT level determined the type of mouse endometrial organoids obtained: high WNT yielded cystic organoids displaying a more differentiated phenotype than the dense organoids obtained in low WNT. The organoids phenocopied physiological responses of endometrial epithelium to hormones, including increased cell proliferation under estrogen and maturation upon progesterone. Moreover, the human endometrial organoids replicated the menstrual cycle under hormonal treatment at both the morpho-histological and molecular levels. Together, we established an organoid culture system for endometrium, reproducing tissue epithelium physiology and allowing long-term expansion. This novel model provides a powerful tool for studying mechanisms underlying the biology as well as the pathology of this key reproductive organ. © 2017. Published by The Company of Biologists Ltd.
Endometrial biopsy findings in postmenopausal bleeding
International Nuclear Information System (INIS)
Sarfraz, T.; Tariq, H.
2007-01-01
To study endometrial histopathology in women presenting with postmenopausal bleeding. A two-year study from January 2003 to December 2004 of 100 cases of postmenopausal bleeding was conducted at Combined Military Hospital, Sialkot. The histopathology of endometrial biopsy specimens was done to find out the causes of postmenopausal bleeding in these ladies. All these 100 patients had confirmed menopause and the average age was 55 years and above. The most common histopathological diagnosis was senile endometrial atrophy (27%), followed by simple cystic hyperplasia in (17%). Three cases of simple cystic hyperplasia had coexistent ovarian tumors. Glandular hyperplasia without atypia was seen in 6% and with atypia in 4%. Other causes were endometritis (13%), endometrial polyps (8%), proliferative phase endometrium (6%) and secretary phase endometrium (5%). Endometrial carcinoma was seen in (6%) cases, (8%) biopsy specimens were non-representative. Although senile endometrial atrophy was most commonly found in these ladies but a significant percentage of endometrial hyperplasia and endometrial cancer implies the need for investigating all cases of postmenopausal bleeding. Bimanual examination and pelvic ultrasonography should be combined with endometrial sampling so that rare pelvic pathologies may not be missed. (author)
Gehrig, Paola A; Cantrell, Leigh A; Shafer, Aaron; Abaid, Lisa N; Mendivil, Alberto; Boggess, John F
2008-10-01
Thirty-three percent of U.S. women are either obese or morbidly obese. This is associated with an increased risk of death from all causes and is also associated with an increased risk of endometrial carcinoma. We sought to compare minimally invasive surgical techniques for staging the obese and morbidly obese woman with endometrial cancer. Consecutive robotic endometrial cancer staging procedures were collected from 2005-2007 and were compared to consecutive laparoscopic cases (2000-2004). Demographics including age, weight, body mass index (BMI), operative time, estimated blood loss, lymph node retrieval, hospital stay and complications were collected and compared. During the study period, there were 36 obese and 13 morbidly obese women who underwent surgery with the DaVinci robotic system and 25 obese and 7 morbidly obese women who underwent traditional laparoscopy. For both the obese and morbidly obese patient, robotic surgery was associated with shorter operative time (p=0.0004), less blood loss (ptool for the comprehensive surgical staging of the obese and morbidly obese woman with endometrial cancer. As this patient population is at increased risk of death from all causes, including post-operative complications, all efforts should be made to improve their outcomes and minimally invasive surgery provides a useful platform by which this can occur.
Nicklin, James; Janda, Monika; Gebski, Val; Jobling, Thomas; Land, Russell; Manolitsas, Tom; McCartney, Anthony; Nascimento, Marcelo; Perrin, Lewis; Baker, Jannah F; Obermair, Andreas
2012-08-15
Surgical staging in early-stage uterine cancer is controversial. Preoperative serum CA-125 may be of clinical value in predicting the presence of extra-uterine disease in patients with apparent early-stage endometrial cancer. Between October 6, 2005, and June 17, 2010, 760 patients were enrolled in an international, multicentre, prospective randomized trial (LACE) comparing laparotomy with laparoscopy in the management of endometrial cancer apparently confined to the uterus. Of these, 657 patients with endometrial adenocarcinoma had a preoperative serum CA-125 value recorded. Multiple cross-validation analysis was undertaken to correlate preoperative serum CA-125 with stage of disease (Stage I vs. Stage II+) after surgery. Patients' median preoperative serum CA-125 was 14 U/ml. A cutoff point of 30 U/ml was associated with the smallest misclassification error, and using this cutoff, 98 patients (14.9%) had elevated CA-125 levels. Of those, 36 (36.7%) had evidence of extra-uterine disease. Of the 116 patients (17.7%) with evidence of extra-uterine disease, 31.0% had an elevated CA-125 level. On univariate and multivariable logistic regression analysis, only preoperative CA-125 level, but no other preoperative clinical characteristics were found to be associated with extra-uterine spread of disease. Utilizing a cutoff point of 30 U/ml achieved a sensitivity, specificity, positive predictive value and negative predictive value of 31.0, 88.5, 36.7 and 85.7%, respectively. Elevated CA-125 above 30 U/ml in patients with apparent early-stage disease is a risk factor for the presence of extra-uterine disease and may assist clinicians in the management of patients with clinical Stage I endometrial cancer. Copyright © 2011 UICC.
Bese, Tugan; Sal, Veysel; Kahramanoglu, Ilker; Tokgozoglu, Nedim; Demirkiran, Fuat; Turan, Hasan; Ilvan, Sennur; Arvas, Macit
2016-02-01
The purpose of this study was to evaluate the clinicopathological characteristics and survival outcomes of women with simultaneous endometrial and ovarian carcinomas having the same histopathologic type. A review of medical records from 1997 to 2015 identified 72 patients with simultaneous carcinomas of the endometrium and ovary with the same histopathologic type. Patients with synchronous primary cancers of endometrium and ovary (SCEOs) were compared with patients with primary endometrial cancer with ovarian metastasis (ECOM). Clinical and pathological data were obtained from the patients' medical records. Clinicopathological variables including categorical data were analyzed by χ(2) or Fisher exact test and continuous data by a Student t test. A Kaplan-Meier survival analysis was performed and compared by using the log-rank test. A univariate and multivariate analysis of 72 patients with SCEO with the same histopathologic type revealed that SCEO is an independent prognostic factor of 10-year overall survival. There were 31 patients in the SCEO group and 41 patients in the ECOM group. With a mean follow-up time of 68.2 months, the 10-year overall survival rates were 61.3% and 36.6% in SCEO and ECOM groups, respectively (P = 0.029). Age, menopausal status, stage of ovarian cancer, performing lymphadenectomy, grade of endometrial tumor, omental metastasis, and residual tumor were found to be significant risk factors for recurrence in the synchronous group. The differentiation between SCEO and ECOM is of great clinical importance while our results showed a better prognosis for patients with SCEO compared with patients with ECOM. More aggressive therapeutic approaches may be considered for patients with SCEO who are older, postmenopausal, and/or have advanced grade of endometrial tumor, omental metastasis, and residual tumor. Lymphadenectomy should be performed in every patient with SCEO.
Diao, Zhen-yu; Lu, Wu-guang; Cao, Peng; Hu, Yun-long; Zhou, Xing; Xue, Ping-ping; Shen, Li; Sun, Hai-xiang
2012-10-01
Nanobody is a kind of antibody from camel, which misses light chain. Nanobody has the same antigen binding specificity and affinity as mAb. Moreover, because of its small molecular weight, high stability and easy preparation, nanobody has great value of biomedical applications. In this study, we successfully prepared highly pure antiEGFR nanobody in E.coli using genetic engineering techniques. Cell proliferation assay (CCK-8 assay) and migration experiments (cell scratch test and Transwell assay) indicated that the recombinant antiEGFRnano can significantly inhibit the proliferation and migration of endometrial cancer cells. These results provide a new way of thinking and methods for EGFR-targeted therapy of endometrial cancer.
Staging of endometrial cancer with MRI: Guidelines of the European Society of Urogenital Imaging
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Kinkel, K. [Geneva University Hospital and Institut de Radiologie, Clinique des Grangettes, Chene-Bougeries/Geneva (Switzerland); Clinique des Grangettes, Institut de radiologie, Chene-Bougerie/Geneva (Switzerland); Forstner, R. [LandesklinikenSalzburg, Zentralroentgeninstitut, Salzburg (Austria); Danza, F.M. [Universita Cattolica del S. Cuore, Dipartimento di Bioimmagini e scienze radiologiche, Rome (Italy); Oleaga, L. [Hospital Clinic, Radiology Department, Barcelona (Spain); Cunha, T.M. [Instituto Portugues de Oncologia de Lisboa Francisco Gentil, Department of Radiology, Lisboa Codex (Portugal); Bergman, A. [Uppsala University Hospital, Department of Radiology, Uppsala (Sweden); Barentsz, J.O. [Radboud University Nijmegen Medical Center, Department of Radiology, Nijmegen (Netherlands); Balleyguier, C. [Institut de Cancerologie Gustave Roussy, Department of Radiology, Villejuif Cedex (France); Brkljacic, B. [University Hospital ' ' Dubrava' ' , Department of Diagnostic and Interventional Radiology, Zagreb (Croatia); University of Zagreb, Medical School, Zagreb (Croatia); Spencer, J.A. [St James' s Institute of Oncology, Department of Clinical Radiology, Leeds (United Kingdom)
2009-07-15
The purpose of this study was to define guidelines for endometrial cancer staging with MRI. The technique included critical review and expert consensus of MRI protocols by the female imaging subcommittee of the European Society of Urogenital Radiology, from ten European institutions, and published literature between 1999 and 2008. The results indicated that high field MRI should include at least two T2-weighted sequences in sagittal, axial oblique or coronal oblique orientation (short and long axis of the uterine body) of the pelvic content. High-resolution post-contrast images acquired at 2 min {+-} 30 s after intravenous contrast injection are suggested to be optimal for the diagnosis of myometrial invasion. If cervical invasion is suspected, additional slice orientation perpendicular to the axis of the endocervical channel is recommended. Due to the limited sensitivity of MRI to detect lymph node metastasis without lymph node-specific contrast agents, retroperitoneal lymph node screening with pre-contrast sequences up to the level of the kidneys is optional. The likelihood of lymph node invasion and the need for staging lymphadenectomy are also indicated by high-grade histology at endometrial tissue sampling and by deep myometrial or cervical invasion detected by MRI. In conclusion, expert consensus and literature review lead to an optimized MRI protocol to stage endometrial cancer. (orig.)
Vaginal vault recurrences of endometrial cancer in non-irradiated patients — Radiotherapy or surgery
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Hordur Alexander Hardarson
2015-01-01
Conclusion: This study indicates that ST is an appropriate treatment for locally recurrent endometrial cancer. Our study involves a limited number of patients and is made retrospectively, therefore prospective and ideally randomized trials evaluating both survival and complications are warranted.
Barry, John A; Azizia, Mallika M; Hardiman, Paul J
2014-01-01
Polycystic ovary syndrome (PCOS) is a common condition affecting ∼8% of women. The objective of the present study was to quantify separately the risk of endometrial cancer, ovarian cancer and breast cancer in women with PCOS compared with non-PCOS controls, and quantify separately the risk to women of all ages as well as the risk to premenopausal women. We conducted a systematic review and meta-analysis of observational studies. Studies were eligible for inclusion if they compared women with PCOS to non-PCOS groups for fatal or non-fatal gynaecological cancers. Studies listed in MEDLINE and EMBASE published up to 7 October 2013 in any language were identified, and relevant papers were also searched by hand. Relevant data (for example, study design, source of control data, diagnostic criteria) were extracted and tabulated. From 698 references, 11 studies (5 of endometrial cancer and 3 each of ovarian and breast cancer) met the inclusion criteria for the meta-analysis (919 women with PCOS and 72054 non-PCOS controls). Using the Mantel-Haenszel method, with fixed or random effects model as appropriate, women with PCOS were at a significantly increased risk of endometrial cancer (odds ratio (OR), 2.79; 95% confidence interval (CI), 1.31-5.95, P cancers was not significantly increased (OR, 1.41; 95% CI, 0.93-2.15, P cancer (OR, 4.05; 95% CI, 2.42-6.76, P cancer (OR, 2.52; 95% CI, 1.08-5.89, P cancer (OR, 0.78; 95% CI, 0.46-1.32, P cancers in women with PCOS younger than 54 years of age compared with controls of similar age. Current data suggest that women of all ages with PCOS are at an increased risk of endometrial cancer but the risk of ovarian and breast cancer was not significantly increased overall. These results highlight the potential risk of gynaecological cancer morbidities associated with PCOS. However, the available evidence is far from robust and variation in diagnostic criteria for PCOS, associated risk factors (particularly obesity), and selection bias
Hughes, Daniel; Baum, George; Jovanovic, Jennifer; Carmack, Cindy; Greisinger, Anthony; Basen-Engquist, Karen
2010-11-01
Self-efficacy can be affected by mastery experiences and somatic sensations. A novel exercise experience and associated sensations may impact self-efficacy and subsequent behaviors. We investigated the effect of a single exercise session on self-efficacy for sedentary endometrial cancer survivors compared with sedentary women of a similar age, but with no cancer history. Twenty survivors and 19 controls completed an exercise session performed as a submaximal cycle ergometry test. Sensations and efficacy were measured before and after exercise. Repeated measures analysis of variance (ANOVA) was performed. Regression models were used to determine predictors of self-efficacy and subsequent exercise. Self-efficacy increased for both survivors and controls, but survivors had a higher rate of increase, and the change predicted subsequent exercise. The association between exercise-related somatic sensations and self-efficacy differed between the 2 groups. A novel exercise experience had a larger effect on self-efficacy and subsequent exercise activity for endometrial cancer survivors than controls. Somatic sensations experienced during exercise may differ for survivors, which may be related to the experience of having cancer. Understanding factors affecting confidence in novel exercise experiences for populations with specific cancer histories is of the utmost importance in the adoption of exercise behaviors.
Frequency of endometrial carcinoma in patients with postmenopausal bleeding
International Nuclear Information System (INIS)
Yousaf, S.; Shaheen, M.; Rana, T.
2010-01-01
Introduction: Postmenopausal bleeding (PMB) is defined as bleeding that occurs after 1 year of amenorrhea in a woman who is not receiving hormone replacement therapy (HRT). About 10% of women with postmenopausal bleeding have a primary or secondary malignancy. Common malignancies among them are endometrial cancer (80%), cervical cancer or an ovarian tumour. Endometrial cancer is the second most common cancer associated with hereditary non-polyposis colorectal cancer. Ninety percent of patients have benign causes. Objective: The objective of this study was to determine the frequency of endometrial carcinoma in patients with post-menopausal bleeding. Study Design: Descriptive case series study. Setting: Department of obstetrics and gynaecology, Lady Willingdon, Lahore. Duration of Study: This study was conducted over a period of six months from January, 1 2009 to June 30, 2009. Subjects and Methods: 50 cases with postmenopausal bleeding. Results: During the period of this study a total number of 50 consecutive patients who met inclusion criteria were enrolled in the study. Ages of the patients who presented with PMB ranged between 48 years and 80 years with a mean age of 59 years. Malignancy was found in 18 out of 50 cases (36%).Cases with endometrial CA were 14 out of 50 cases (28%) and CA cervix constituted 4 out of 50 cases (8%). Benign pathology was more frequent (64%). 13 of 50 cases (26%) had hyperplasia out of which 1 case (2%) was of atypical hyperplasia. Endometrial polyp was found in 4 of 50 cases (8%). 3 of 50 cases (6%) had chronic endometritis. 5 of 50 cases (10%) had chronic cervicitis. While 7 cases (14%) had postmenopausal bleeding due to decubitus ulcer of uterovaginal prolapse. Among malignancies (36%), endometrial cancer is the most frequent malignancy in women with postmenopausal bleeding with mean age of 65 years. Conclusion: In this study it was concluded that the majority of cases of PMB would be expected to be suffering from benign problems
van Hanegem, Nehalennia; Prins, Marileen M. C.; Bongers, Marlies Y.; Opmeer, Brent C.; Sahota, Daljit Singh; Mol, Ben Willem J.; Timmermans, Anne
2016-01-01
Postmenopausal bleeding (PMB) can be the first sign of endometrial cancer. In case of thickened endometrium, endometrial sampling is often used in these women. In this systematic review, we studied the accuracy of endometrial sampling for the diagnoses of endometrial cancer, atypical hyperplasia and
Clinical and cytological definition of endometrial cancer during radiotherapy
International Nuclear Information System (INIS)
Titova, V.A.; Titova, N.P.
1981-01-01
The state of primary tumor in 45 patients with adenocarcinoma of the endometrium, stage 1-3, during concomitant radical radio-and hormonotherapy according to the data of hysterocervicography, hysterometry and cytohistology have been studied. Contact irradiation was performed in single fractions of 9.5-10.0 Gy per week. The time course of primary uterine tumor regression was observed with regard to various radiation dose levels in accordance with cytological data. The cytological method is regarded as an important quantitative criterion in the evaluation of radio- and hormonotherapeutic efficacy of inoperable endometrial cancer [ru
Directory of Open Access Journals (Sweden)
Chunxiao Zhou
Full Text Available Given that prolonged exposure to estrogen and increased telomerase activity are associated with endometrial carcinogenesis, our objective was to evaluate the interaction between the MAPK pathway and estrogen induction of telomerase activity in endometrial cancer cells. Estradiol (E2 induced telomerase activity and hTERT mRNA expression in the estrogen receptor (ER-α positive, Ishikawa endometrial cancer cell line. UO126, a highly selective inhibitor of MEK1/MEK2, inhibited telomerase activity and hTERT mRNA expression induced by E2. Similar results were also found after transfection with ERK 1/2-specific siRNA. Treatment with E2 resulted in rapid phosphorylation of p44/42 MAPK and increased MAPK activity which was abolished by UO126. The hTERT promoter contains two estrogen response elements (EREs, and luciferase assays demonstrate that these EREs are activated by E2. Exposure to UO126 or ERK 1/2-specific siRNA in combination with E2 counteracted the stimulatory effect of E2 on luciferase activity from these EREs. These findings suggest that E2-induction of telomerase activity is mediated via the MAPK pathway in human endometrial cancer cells.
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Kim, Ji Young; Lee, Kyung Ja; Park, Kyung Ran [Dept. of Radiation Oncology, Ewha Womans University School of Medicine, Seoul (Korea, Republic of); and others
2016-12-15
The purpose of this study is to evaluate the treatment outcomes of adjuvant radiotherapy using vaginal brachytherapy (VB) with a lower dose per fraction and/or external beam radiotherapy (EBRT) following surgery for patients with stage I endometrial carcinoma. The subjects were 43 patients with the International Federation of Gynecology and Obstetrics (FIGO) stage I endometrial cancer who underwent adjuvant radiotherapy following surgery between March 2000 and April 2014. Of these, 25 received postoperative VB alone, while 18 received postoperative EBRT to the whole pelvis; 3 of these were treated with EBRT plus VB. The median EBRT dose was 50.0 Gy (45.0–50.4 Gy) and the VB dose was 24 Gy in 6 fractions. Tumor dose was prescribed at a depth of 5 mm from the cylinder surface and delivered twice per week. The median follow-up period for all patients was 57 months (range, 9 to 188 months). Five-year disease-free survival (DFS) and overall survival (OS) for all patients were 92.5% and 95.3%, respectively. Adjuvant radiotherapy was performed according to risk factors and stage IB, grade 3 and lymphovascular invasion were observed more frequently in the EBRT group. Five-year DFS for EBRT and VB alone were 88.1% and 96.0%, respectively (p = 0.42), and 5-year OS for EBRT and VB alone were 94.4% and 96%, respectively (p = 0.38). There was no locoregional recurrence in any patient. Two patients who received EBRT and 1 patient who received VB alone developed distant metastatic disease. Two patients who received EBRT had severe complications, one each of grade 3 gastrointestinal complication and pelvic bone insufficiency fracture. Adjuvant radiotherapy achieved high DFS and OS with acceptable toxicity in stage I endometrial cancer. VB (with a lower dose per fraction) may be a viable option for selected patients with early-stage endometrial cancer following surgery.
DEFF Research Database (Denmark)
Greimel, Elfriede; Nordin, Andy; Lanceley, Anne
2011-01-01
A validation study was conducted to evaluate the psychometric properties of the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Endometrial Cancer Module (EORTC QLQ-EN24). This module was designed to assess disease and treatment specific aspects of...
Altwerger, Gary; Bonazzoli, Elena; Bellone, Stefania; Egawa-Takata, Tomomi; Menderes, Gulden; Pettinella, Francesca; Bianchi, Anna; Riccio, Francesco; Feinberg, Jacqueline; Zammataro, Luca; Han, Chanhee; Yadav, Ghanshyam; Dugan, Katherine; Morneault, Ashley; Ponte, Jose F; Buza, Natalia; Hui, Pei; Wong, Serena; Litkouhi, Babak; Ratner, Elena; Silasi, Dan-Arin; Huang, Gloria S; Azodi, Masoud; Schwartz, Peter E; Santin, Alessandro D
2018-05-01
Grade 3 endometrioid and uterine serous carcinomas (USC) account for the vast majority of endometrial cancer deaths. The purpose of this study was to determine folic acid receptor alpha (FRα) expression in these biologically aggressive (type II) endometrial cancers and evaluate FRα as a targetable receptor for IMGN853 (mirvetuximab soravtansine). The expression of FRα was evaluated by immunohistochemistry (IHC) and flow cytometry in 90 endometrioid and USC samples. The in vitro cytotoxic activity and bystander effect were studied in primary uterine cancer cell lines expressing differential levels of FRα. In vivo antitumor efficacy of IMGN853 was evaluated in xenograft/patient-derived xenograft (PDX) models. Semiquantitative IHC analysis indicated that 41% of the USC patients overexpress FRα. Further, overexpression of FRα (i.e., 2+) was detected via flow cytometry in 22% (2/9) of primary endometrioid and in 27% (3/11) of primary USC cell lines. Increased cytotoxicity was seen with IMGN853 treatment compared with control in 2+ expressing uterine tumor cell lines. In contrast, tumor cell lines with low FRα showed no difference when exposed to IMGN853 versus control. IMGN853 induced bystander killing of FRα = 0 tumor cells. In an endometrioid xenograft model (END(K)265), harboring 2+ FRα, IMGN853 treatment showed complete resolution of tumors ( P USC PDX model (BIO(K)1), expressing 2+ FRα, induced twofold increase in median survival ( P < 0.001). IMGN853 shows impressive antitumor activity in biologically aggressive FRα 2+ uterine cancers. These preclinical data suggest that patients with chemotherapy resistant/recurrent endometrial cancer overexpressing FRα may benefit from this treatment. Mol Cancer Ther; 17(5); 1003-11. ©2018 AACR . ©2018 American Association for Cancer Research.
Endometrial Intraepithelial Neoplasia (EIN In An Endometrial Polyp
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Devic Ana
2015-12-01
Full Text Available Endometrial intraepithelial neoplasia (EIN is a monoclonal neoplastic cell proliferation of the endometrium associated with a significantly increased risk of endometrioid endometrial adenocarcinoma. We herein present the case of a 58-year-old female patient who underwent a hysterectomy with bilateral salpingo-oophorectomy because of the existence of endometrial intraepithelial neoplasia in an endometrial polyp. The patient had irregular uterine bleeding, which lasted 10 days. An endometrial polyp was diagnosed by ultrasound examination. The polyp was located in the isthmus of the uterus, on the back wall, and measured 32 mm × 25 mm. The patient underwent fractional dilation and curettage, and the specimens were subjected to a histopathological examination. The histopathological findings were EIN, endometrioid type, a focus of which was found within the endometrial polyps, as well as the endometrial polyp and proliferative endometrium. The endocervical tissue was normal. Given the age of the patient and the histopathological findings, she underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy. The final histopathological findings were EIN, endometrioid type with a focus found within the endometrial polyp; endometrial polyp; simple hyperplasia; chronic inflammation of the uterine cervix; hyperkeratosis of the cervical squamous epithelium; and cervicitis chronica. There was also hydrosalpinx of the left fallopian tube, and cystic follicles in the left ovary. There was no significant morphological change in the right ovary or fallopian tube. The surgical and postoperative course were normal. The patient was sent home on the fifth postoperative day in good general condition. A check-up performed one month after surgery showed normal findings.
Antitumor effects of cecropin B-LHRH’ on drug-resistant ovarian and endometrial cancer cells
International Nuclear Information System (INIS)
Li, Xiaoyong; Shen, Bo; Chen, Qi; Zhang, Xiaohui; Ye, Yiqing; Wang, Fengmei; Zhang, Xinmei
2016-01-01
Luteinizing hormone-releasing hormone receptor (LHRHr) represents a promising therapeutic target for treating sex hormone-dependent tumors. We coupled cecropin B, an antimicrobial peptide, to LHRH’, a form of LHRH modified at carboxyl-terminal residues 4–10, which binds to LHRHr without interfering with luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion. This study aimed to assess the antitumor effects of cecropin B-LHRH’ (CB-LHRH’) in drug-resistant ovarian and endometrial cancers. To evaluate the antitumor effects of CB-LHRH’, three drug resistant ovarian cancer cell lines (SKOV-3, ES-2, NIH:OVCAR-3) and an endometrial cancer cell line (HEC-1A) were treated with CB-LHRH’. Cell morphology changes were assessed using inverted and electron microscopes. In addition, cell growth and cell cytotoxicity were measured by MTT assay and LDH release, respectively. In addition, hemolysis was measured. Furthermore, radioligand receptor binding, hypersensitization and minimal inhibitory concentrations (against Staphylococcus aureus, Klebsiella pneumoniae, Escherichia coli, Enterobacter cloacae, Pseudomonas aeruginosa, and Acinetobacter baumannii) were determined. Finally, the impact on tumor growth in BALB/c-nu mice was assessed in an ES-2 xenograft model. CB-LHRH’ bound LHRHr with high-affinity (dissociation constant, Kd = 0.252 ± 0.061nM). Interestingly, CB-LHRH’ significantly inhibited the cell viability of SKOV-3, ES-2, NIH:OVCAR-3 and HEC-1A, but not that of normal eukaryotic cells. CB-LHRH’ was active against bacteria at micromolar concentrations, and caused no hypersensitivity in guinea pigs. Furthermore, CB-LHRH’ inhibited tumor growth with a 23.8 and 20.4 % reduction in tumor weight at 50 and 25 mg/kg.d, respectively. CB-LHRH’ is a candidate for targeted chemotherapy against ovarian and endometrial cancers
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Ota, Takashi; Hori, Masatoshi; Onishi, Hiromitsu; Sakane, Makoto; Tsuboyama, Takahiro; Tatsumi, Mitsuaki; Tomiyama, Noriyuki [Osaka University Graduate School of Medicine, Department of Diagnostic and Interventional Radiology, Suita, Osaka (Japan); Nakamoto, Atsushi; Narumi, Yoshifumi [Osaka Medical College, Department of Radiology, Osaka (Japan); Kimura, Tadashi [Osaka University Graduate School of Medicine, Department of Obstetrics and Gynaecology, Osaka (Japan)
2017-12-15
To compare the image quality and diagnostic performance of reduced field-of-view (rFOV) versus conventional full field-of-view (fFOV) diffusion-weighted (DW) imaging of endometrial cancer. Fifty women with endometrial cancer underwent preoperative rFOV and fFOV DW imaging. Two radiologists compared the image qualities of both techniques, and five radiologists assessed superficial and deep myometrial invasion using both techniques. The statistical analysis included the Wilcoxon signed-rank test and paired t-test for comparisons of image quality and mean diagnostic values. Distortion, tumour delineation, and overall image quality were significantly better with rFOV DW imaging, compared to fFOV DW imaging (P < 0.05); however, the former was inferior in noise (P < 0.05). Regarding superficial invasion, the mean accuracies of the techniques did not differ statistically (rFOV, 58.0% versus fFOV, 56.0%; P = 0.30). Regarding deep myometrial invasion, rFOV DW imaging yielded significantly better mean accuracy, specificity, and positive predictive values (88.4%, 97.8%, and 91.7%, respectively), compared with fFOV DW imaging (84.8%, 94.1%, and 77.4%, respectively; P = 0.009, 0.005, and 0.011, respectively). Compared with fFOV DW imaging, rFOV DW imaging yielded less distortion, improved image quality and, consequently, better diagnostic performance for deep myometrial invasion of endometrial cancer. (orig.)
International Nuclear Information System (INIS)
Rechichi, Gilda; Sironi, Sandro; Galimberti, Stefania; Valsecchi, Maria Grazia; Signorelli, Mauro; Perego, Patrizia
2010-01-01
To determine the diagnostic accuracy of diffusion-weighted (DW) magnetic resonance (MR) imaging in the preoperative assessment of myometrial invasion by endometrial cancer. In this prospective study, 47 patients with histologically confirmed endometrial cancer underwent preoperative MR imaging and total hysterectomy. The MR protocol included spin-echo multishot T2-weighted, dynamic T1-weighted and DW images acquired with b-values of 0 and 500 s/mm 2 . Myometrial tumour spread was classified as superficial (<50%) or deep (≥50% myometrial thickness). Postoperative histopathological findings served as a reference standard. Indices of diagnostic performance were assessed for each sequence. At histopathological examination, superficial myometrial invasion was found in 34 patients and deep myometrial invasion in 13. In the assessment of tumour invasion, sensitivity, specificity, positive and negative predictive values of T2-weighted images were 92.3%, 76.5%, 60.0% and 96.3%, respectively. The corresponding values for dynamic images were 69.2%, 61.8%, 40.9% and 84.0%, and for DW images 84.6%, 70.6%, 52.4% and 92.3%. T2-weighted and DW imaging proved to be the most accurate techniques for tumour spread determination. DW imaging proved to be accurate in assessing myometrial invasion, and it could replace dynamic imaging as an adjunct to routine T2-weighted imaging for preoperative evaluation of endometrial cancer. (orig.)
Prevalence of Lynch syndrome among patients with newly diagnosed endometrial cancers.
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Cecilia Egoavil
Full Text Available Lynch syndrome (LS is a hereditary condition that increases the risk for endometrial and other cancers. The identification of endometrial cancer (EC patients with LS has the potential to influence life-saving interventions. We aimed to study the prevalence of LS among EC patients in our population.Universal screening for LS was applied for a consecutive series EC. Tumor testing using microsatellite instability (MSI, immunohistochemistry (IHC for mismatch-repair (MMR protein expression and MLH1-methylation analysis, when required, was used to select LS-suspicious cases. Sequencing of corresponding MMR genes was performed.One hundred and seventy-three EC (average age, 63 years were screened. Sixty-one patients (35% had abnormal IHC or MSI results. After MLH1 methylation analysis, 27 cases were considered suspicious of LS. From these, 22 were contacted and referred for genetic counseling. Nineteen pursued genetic testing and eight were diagnosed of LS. Mutations were more frequent in younger patients (<50 yrs. Three cases had either intact IHC or MSS and reinforce the need of implement the EC screening with both techniques.The prevalence of LS among EC patients was 4.6% (8/173; with a predictive frequency of 6.6% in the Spanish population. Universal screening of EC for LS is recommended.
BAG3 Protein Is Over-Expressed in Endometrioid Endometrial Adenocarcinomas.
Esposito, Veronica; Baldi, Carlo; Zeppa, Pio; Festa, Michelina; Guerriero, Luana; d'Avenia, Morena; Chetta, Massimiliano; Zullo, Fulvio; De Laurenzi, Vincenzo; Turco, Maria Caterina; Rosati, Alessandra; Guida, Maurizio
2017-02-01
Endometrioid endometrial cancer is the most common gynaecological tumor in developed countries, and its incidence is increasing. The definition of subtypes, based on clinical and endocrine features or on histopathological characteristics, correlate to some extent with patient's prognosis, but there is substantial heterogeneity within tumor types. The search for molecules and mechanisms implied in determining the progression and the response to therapy for this cancer is still ongoing. BAG3 protein, a member of BAG family of co-chaperones, has a pro-survival role in several tumor types. BAG3 anti-apoptotic properties rely on its characteristic to bind several intracellular partners, thereby, modulating crucial events such as apoptosis, differentiation, cell motility, and autophagy. BAG3 expression in human endometrial cancer tissues was not investigated so far. Here, we show that BAG3 protein levels are elevated in tumoral and hyperplastic cells in respect to normal glands. Furthermore, BAG3 subcellular localization appears to be changed in tumoral compared to normal cells. Our results indicate a possible role for BAG3 protein in the maintenance of cell survival in endometrioid endometrial cancer and suggest that this field of studies is worthy of further investigations. J. Cell. Physiol. 232: 309-311, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
Staging of endometrial cancer with MRI: Guidelines of the European Society of Urogenital Imaging
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Kinkel, K.; Forstner, R.; Danza, F.M.; Oleaga, L.; Cunha, T.M.; Bergman, A.; Barentsz, J.O.; Balleyguier, C.; Brkljacic, B.; Spencer, J.A.
2009-01-01
The purpose of this study was to define guidelines for endometrial cancer staging with MRI. The technique included critical review and expert consensus of MRI protocols by the female imaging subcommittee of the European Society of Urogenital Radiology, from ten European institutions, and published literature between 1999 and 2008. The results indicated that high field MRI should include at least two T2-weighted sequences in sagittal, axial oblique or coronal oblique orientation (short and long axis of the uterine body) of the pelvic content. High-resolution post-contrast images acquired at 2 min ± 30 s after intravenous contrast injection are suggested to be optimal for the diagnosis of myometrial invasion. If cervical invasion is suspected, additional slice orientation perpendicular to the axis of the endocervical channel is recommended. Due to the limited sensitivity of MRI to detect lymph node metastasis without lymph node-specific contrast agents, retroperitoneal lymph node screening with pre-contrast sequences up to the level of the kidneys is optional. The likelihood of lymph node invasion and the need for staging lymphadenectomy are also indicated by high-grade histology at endometrial tissue sampling and by deep myometrial or cervical invasion detected by MRI. In conclusion, expert consensus and literature review lead to an optimized MRI protocol to stage endometrial cancer. (orig.)
The prognostic role of classical and nonclassical MHC class I expression in endometrial cancer
Bijen, C.B.; Bantema-Joppe, E.J.; de Jong, Renske; Leffers, N.; Mourits, M.J.; Eggink, Henk F.; van der Zee, A.G.; Hollema, H.; de Bock, G.H.; Nijman, H.W.
2010-01-01
The aim of this study was to investigate classical MHC class I and nonclassical MHC (human leukocyte antigen-G [HLA-GJ) expression in a large cohort of patients with endometrial cancer, to determine the prognostic value of these cell surface markers and their relation with clinicopathological
A systematic review of tests for lymph node status in primary endometrial cancer.
Selman, Tara J; Mann, Christopher H; Zamora, Javier; Khan, Khalid S
2008-05-05
The lymph node status of a patient is a key determinate in staging, prognosis and adjuvant treatment of endometrial cancer. Despite this, the potential additional morbidity associated with lymphadenectomy makes its role controversial. This study systematically reviews the accuracy literature on sentinel node biopsy; ultra sound scanning, magnetic resonance imaging (MRI) and computer tomography (CT) for determining lymph node status in endometrial cancer. Relevant articles were identified form MEDLINE (1966-2006), EMBASE (1980-2006), MEDION, the Cochrane library, hand searching of reference lists from primary articles and reviews, conference abstracts and contact with experts in the field. The review included 18 relevant primary studies (693 women). Data was extracted for study characteristics and quality. Bivariate random-effect model meta-analysis was used to estimate diagnostic accuracy of the various index tests. MRI (pooled positive LR 26.7, 95% CI 10.6 - 67.6 and negative LR 0.29 95% CI 0.17 - 0.49) and successful sentinel node biopsy (pooled positive LR 18.9 95% CI 6.7 - 53.2 and negative LR 0.22, 95% CI 0.1 - 0.48) were the most accurate tests. CT was not as accurate a test (pooled positive LR 3.8, 95% CI 2.0 - 7.3 and negative LR of 0.62, 95% CI 0.45 - 0.86. There was only one study that reported the use of ultrasound scanning. MRI and sentinel node biopsy have shown similar diagnostic accuracy in confirming lymph node status among women with primary endometrial cancer than CT scanning, although the comparisons made are indirect and hence subject to bias. MRI should be used in preference, in light of the ASTEC trial, because of its non invasive nature.
A systematic review of tests for lymph node status in primary endometrial cancer
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Zamora Javier
2008-05-01
Full Text Available Abstract Background The lymph node status of a patient is a key determinate in staging, prognosis and adjuvant treatment of endometrial cancer. Despite this, the potential additional morbidity associated with lymphadenectomy makes its role controversial. This study systematically reviews the accuracy literature on sentinel node biopsy; ultra sound scanning, magnetic resonance imaging (MRI and computer tomography (CT for determining lymph node status in endometrial cancer. Methods Relevant articles were identified form MEDLINE (1966–2006, EMBASE (1980–2006, MEDION, the Cochrane library, hand searching of reference lists from primary articles and reviews, conference abstracts and contact with experts in the field. The review included 18 relevant primary studies (693 women. Data was extracted for study characteristics and quality. Bivariate random-effect model meta-analysis was used to estimate diagnostic accuracy of the various index tests. Results MRI (pooled positive LR 26.7, 95% CI 10.6 – 67.6 and negative LR 0.29 95% CI 0.17 – 0.49 and successful sentinel node biopsy (pooled positive LR 18.9 95% CI 6.7 – 53.2 and negative LR 0.22, 95% CI 0.1 – 0.48 were the most accurate tests. CT was not as accurate a test (pooled positive LR 3.8, 95% CI 2.0 – 7.3 and negative LR of 0.62, 95% CI 0.45 – 0.86. There was only one study that reported the use of ultrasound scanning. Conclusion MRI and sentinel node biopsy have shown similar diagnostic accuracy in confirming lymph node status among women with primary endometrial cancer than CT scanning, although the comparisons made are indirect and hence subject to bias. MRI should be used in preference, in light of the ASTEC trial, because of its non invasive nature.
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Yen Ling Low
2010-07-01
Full Text Available Despite the central role of estrogen exposure in breast and endometrial cancer development and numerous studies of genes in the estrogen metabolic pathway, polymorphisms within the pathway have not been consistently associated with these cancers. We posit that this is due to the complexity of multiple weak genetic effects within the metabolic pathway that can only be effectively detected through multi-variant analysis. We conducted a comprehensive association analysis of the estrogen metabolic pathway by interrogating 239 tagSNPs within 35 genes of the pathway in three tumor samples. The discovery sample consisted of 1,596 breast cancer cases, 719 endometrial cancer cases, and 1,730 controls from Sweden; and the validation sample included 2,245 breast cancer cases and 1,287 controls from Finland. We performed admixture maximum likelihood (AML-based global tests to evaluate the cumulative effect from multiple SNPs within the whole metabolic pathway and three sub-pathways for androgen synthesis, androgen-to-estrogen conversion, and estrogen removal. In the discovery sample, although no single polymorphism was significant after correction for multiple testing, the pathway-based AML global test suggested association with both breast (p(global = 0.034 and endometrial (p(global = 0.052 cancers. Further testing revealed the association to be focused on polymorphisms within the androgen-to-estrogen conversion sub-pathway, for both breast (p(global = 0.008 and endometrial cancer (p(global = 0.014. The sub-pathway association was validated in the Finnish sample of breast cancer (p(global = 0.015. Further tumor subtype analysis demonstrated that the association of the androgen-to-estrogen conversion sub-pathway was confined to postmenopausal women with sporadic estrogen receptor positive tumors (p(global = 0.0003. Gene-based AML analysis suggested CYP19A1 and UGT2B4 to be the major players within the sub-pathway. Our study indicates that the composite
The impact of 27-hydroxycholesterol on endometrial cancer proliferation.
Gibson, Douglas A; Collins, Frances; Cousins, Fiona L; Esnal Zufiaurre, Arantza; Saunders, Philippa T K
2018-04-01
Endometrial cancer (EC) is the most common gynaecological malignancy. Obesity is a major risk factor for EC and is associated with elevated cholesterol. 27-hydroxycholesterol (27HC) is a cholesterol metabolite that functions as an endogenous agonist for Liver X receptor (LXR) and a selective oestrogen receptor modulator (SERM). Exposure to oestrogenic ligands increases risk of developing EC; however, the impact of 27HC on EC is unknown. Samples of stage 1 EC ( n = 126) were collected from postmenopausal women undergoing hysterectomy. Expression of LXRs ( NR1H3 , LXRα; NR1H2 , LXRβ) and enzymes required for the synthesis ( CYP27A1 ) or breakdown ( CYP7B1 ) of 27HC were detected in all grades of EC. Cell lines originating from well-, moderate- and poorly-differentiated ECs (Ishikawa, RL95, MFE 280 respectively) were used to assess the impact of 27HC or the LXR agonist GW3965 on proliferation or expression of a luciferase reporter gene under the control of LXR- or ER-dependent promoters (LXRE, ERE). Incubation with 27HC or GW3965 increased transcription via LXRE in Ishikawa, RL95 and MFE 280 cells ( P MFE 280 cells, 27HC did not alter proliferation but selective targeting of LXR with GW3965 significantly reduced cell proliferation ( P < 0.0001). These novel results suggest that 27HC can contribute to risk of EC by promoting proliferation of endometrial cancer epithelial cells and highlight LXR as a potential therapeutic target in the treatment of advanced disease. © 2018 The authors.
TET1-GPER-PI3K/AKT pathway is involved in insulin-driven endometrial cancer cell proliferation
International Nuclear Information System (INIS)
Xie, Bing-ying; Lv, Qiao-ying; Ning, Cheng-cheng; Yang, Bing-yi; Shan, Wei-wei; Cheng, Ya-li; Gu, Chao; Luo, Xue-zhen; Zhang, Zhen-bo; Chen, Xiao-jun; Xi, Xiao-wei; Feng, You-ji
2017-01-01
Large amount of clinical evidence has demonstrated that insulin resistance is closely related to oncogenesis of endometrial cancer (EC). Despite recent studies showed the up-regulatory role of insulin in G protein-coupled estrogen receptor (GPER/GPR30) expression, GPER expression was not decreased compared to control when insulin receptor was blocked even in insulin treatment. The purpose of this study was to explore the possible mechanism by which insulin up-regulates GPER that drives EC cell proliferation. For this purpose, we first investigated the GPER expression in tissues of endometrial lesions, further explored the effect of GPER on EC cell proliferation in insulin resistance context. Then we analyzed the role of Ten-Eleven Translocation 1 (TET1) in insulin-induced GEPR expression and EC cell proliferation. The results showed that GPER was highly expressed in endometrial atypical hyperplasia and EC tissues. Mechanistically, insulin up-regulated TET1 expression and the latter played an important role in up-regulating GPER expression and activating PI3K/AKT signaling pathway. TET1 mediated GPER up-regulation was another mechanism that insulin promotes EC cell proliferation. - Highlights: • GPER acts as an oncogene to drive EC cell growth in insulin resistance context. • TET1 is associated with insulin-induced GPER expression. • Insulin resistance contributed to EC through TET1-GPER-PI3K/AKT pathway.
Palomba, Stefano; Falbo, Angela; Russo, Tiziana; La Sala, Giovanni Battista
2012-01-01
Port-site metastases, also called trocar-site metastasis, have been described after laparoscopic surgery for non-gynecological and gynecological cancers. The aim of this review was to obtain evidence for port-site metastases after laparoscopic surgical staging of endometrial cancer. A systematic search of published and unpublished cases of port-site metastases after laparoscopic staging of endometrial cancer was conducted. All the authors responsible for correspondence were contacted to obtain any missing data. The patients' characteristics and oncologic, surgical, and safety data were recorded and analyzed. Twelve cases of port-site metastases were identified and examined. In 4 cases they were "isolated," that is, recurrence without association with peritoneal carcinomatosis, whereas in 8 cases they were "nonisolated." The port-site metastases did not occur as a result of trocar site localization or dimension. No univocal strategy to prevent port-site metastases was adopted. Among patients with nonisolated port-site metastases, an aggressive histologic condition and a high grade were found in 3 of 6 patients and in 3 of 5 patients, respectively. Among patients with isolated port-site metastases, an early-stage endometrioid adenocarcinoma G2 endometrial cancer and a stage IIB G2 endometrioid adenocarcinoma were described in 3 of 4 patients and in only 1 case, respectively. All the patients with nonisolated port-site metastases died of disease. Similarly, among patients with isolated port-site metastases, only 1 was alive and free of disease after 10 months from recurrence diagnosis. Port-site metastases of endometrial cancer are an entity rarely reported but probably the expression of an aggressive disease. The available data do not allow us to draw conclusions or suggestions for their prevention and the treatment. Copyright © 2012 AAGL. Published by Elsevier Inc. All rights reserved.
Alonso-Alconada, Lorena; Muinelo-Romay, Laura; Madissoo, Kadri; Diaz-Lopez, Antonio; Krakstad, Camilla; Trovik, Jone; Wik, Elisabeth; Hapangama, Dharani; Coenegrachts, Lieve; Cano, Amparo; Gil-Moreno, Antonio; Chiva, Luis; Cueva, Juan; Vieito, Maria; Ortega, Eugenia; Mariscal, Javier; Colas, Eva; Castellvi, Josep; Cusido, Maite; Dolcet, Xavier; Nijman, Hans W.; Bosse, Tjalling; Green, John A.; Romano, Andrea; Reventos, Jaume; Lopez-Lopez, Rafael; Salvesen, Helga B.; Amant, Frederic; Matias-Guiu, Xavier; Moreno-Bueno, Gema; Abal, Miguel
2014-01-01
Background: About 20% of patients diagnosed with endometrial cancer (EC) are considered high-risk with unfavorable prognosis. In the framework of the European Network for Individualized Treatment in EC (ENITEC), we investigated the presence and phenotypic features of Circulating Tumor Cells (CTC) in
Franchi, Matteo; Asciutto, Rosario; Nicotra, Federica; Merlino, Luca; La Vecchia, Carlo; Corrao, Giovanni; Bosetti, Cristina
2017-05-01
Metformin may reduce the risk of endometrial cancer whereas other drugs for the treatment of type 2 diabetes mellitus appear to increase it, although the evidence is still limited. We investigated this issue using data from a nested case-control study within the healthcare utilization databases of the Lombardy Region, Italy. This study included 376 diabetic women with endometrial cancer and 7485 diabetic controls matched for cases on age, date at cohort entry, and duration of follow-up. We used conditional logistic regression models to estimate the odds ratio (OR) of endometrial cancer in relation to use of antidiabetic drugs, adjusted for the Charlson's comorbidity index, selected medical conditions, prescription of selected drugs, and concomitant use of other antidiabetic drugs. At cohort entry, no significant associations were observed for metformin [OR=0.99, 95% confidence interval (CI) 0.80-1.23], sulfonylureas (OR=1.14, 95% CI 0.91-1.42), insulin (OR=0.72, 95% CI 0.34-1.56), and other antidiabetic drugs (OR=1.21, 95% CI 0.75-1.95). When we considered use during follow-up, a borderline significant excess risk was found for metformin (OR=1.30, 95% CI 1.00-1.70). However, this estimate decreased to 1.07 (95% CI 0.82-1.41) when taking into account BMI using a Monte Carlo sensitivity analysis. No significant associations were found for sulfonylureas (OR=1.16, 95% CI 0.91-1.47), thiazolidinediones (OR=0.77, 95% CI 0.48-1.24), repaglinide (OR=1.32, 95% CI 0.94-1.87), incretins (OR=1.21, 95% CI 0.63-2.32), and insulin (OR=1.19, 95% CI 0.82-1.71). Our data indicate that metformin, insulin, and other antidiabetic drugs did not meaningfully affect the risk of endometrial cancer.
An update of the classical Bokhman’s dualistic model of endometrial cancer
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Miłosz Wilczyński
2016-07-01
Full Text Available According to the classical dualistic model introduced by Bokhman in 1983, endometrial cancer (EC is divided into two basic types. The prototypical histological type for type I and type II of EC is endometrioid carcinoma and serous carcinoma, respectively. The traditional classification is based on clinical, endocrine and histopathological features, however, it sometimes does not reflect the full heterogeneity of EC. New molecular evidence, supported by clinical diversity of the cancer, indicates that the classical dualistic model is valid only to some extent. The review updates a mutational diversity of EC, introducing a new molecular classification of the tumour in regard to data presented by The Cancer Genome Atlas Research Network (TGCA.
Needs and priorities of women with endometrial and cervical cancer
DEFF Research Database (Denmark)
Jeppesen, Mette Moustgaard; Mogensen, Ole; Dehn, Pernille
2015-01-01
modality and marital status severely impacted on coping, suggesting that irradiated and single women are at higher risk of developing rehabilitation needs. Additionally, women younger than 55 years more often requested help dealing with sexual and psychological complications. DISCUSSION: Women......INTRODUCTION: Rehabilitation after cancer is important, and efficient rehabilitation requires knowledge of patient's needs. This study aimed to identify short-term rehabilitation needs of women with endometrial and cervical cancer. METHODS: Ninety-six women (82.6%) were included in an exploratory...... questionnaire study from Odense University Hospital from September 2011 to March 2012. Needs were assessed pre-treatment and 3 months later using the three-levels-of-needs questionnaire. Furthermore, 16 women participated in focus group interviews following the treatment. The interviews were audio...
International Nuclear Information System (INIS)
Barney, Brandon M.; Petersen, Ivy A.; Mariani, Andrea; Dowdy, Sean C.; Bakkum-Gamez, Jamie N.; Haddock, Michael G.
2013-01-01
Objectives: The optimal adjuvant therapy for International Federation of Gynecology and Obstetrics (FIGO) stage I papillary serous (UPSC) or clear cell (CC) endometrial cancer is unknown. We report on the largest single-institution experience using adjuvant high-dose-rate vaginal brachytherapy (VBT) for surgically staged women with FIGO stage I UPSC or CC endometrial cancer. Methods and Materials: From 1998-2011, 103 women with FIGO 2009 stage I UPSC (n=74), CC (n=21), or mixed UPSC/CC (n=8) endometrial cancer underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy followed by adjuvant high-dose-rate VBT. Nearly all patients (n=98, 95%) also underwent extended lymph node dissection of pelvic and paraortic lymph nodes. All VBT was performed with a vaginal cylinder, treating to a dose of 2100 cGy in 3 fractions. Thirty-five patients (34%) also received adjuvant chemotherapy. Results: At a median follow-up time of 36 months (range, 1-146 months), 2 patients had experienced vaginal recurrence, and the 5-year Kaplan Meier estimate of vaginal recurrence was 3%. The rates of isolated pelvic recurrence, locoregional recurrence (vaginal + pelvic), and extrapelvic recurrence (including intraabdominal) were similarly low, with 5-year Kaplan-Meier estimates of 4%, 7%, and 10%, respectively. The estimated 5-year overall survival was 84%. On univariate analysis, delivery of chemotherapy did not affect recurrence or survival. Conclusions: VBT is effective at preventing vaginal relapse in women with surgical stage I UPSC or CC endometrial cancer. In this cohort of patients who underwent comprehensive surgical staging, the risk of isolated pelvic or extrapelvic relapse was low, implying that more extensive adjuvant radiation therapy is likely unnecessary.
de Boer, Stephanie M.; Powell, Melanie E.; Mileshkin, Linda; Katsaros, Dionyssios; Bessette, Paul; Haie-Meder, Christine; Ottevanger, Petronella B.; Ledermann, Jonathan A.; Khaw, Pearly; Colombo, Alessandro; Fyles, Anthony; Baron, Marie-Helene; Kitchener, Henry C.; Nijman, Hans W.; Kruitwagen, Roy F.; Nout, Remi A.; Verhoeven-Adema, Karen W.; Smit, Vincent T.; Putter, Hein; Creutzberg, Carien L.
Background About 15% of patients with endometrial cancer have high-risk features and are at increased risk of distant metastases and endometrial cancer-related death. We designed the PORTEC-3 trial to investigate the benefit of adjuvant chemoradiotherapy compared with radiotherapy alone for women
Boer, S.M. de; Powell, M.E.; Mileshkin, L.; Katsaros, D.; Bessette, P.; Haie-Meder, C.; Ottevanger, P.B.; Ledermann, J.A.; Khaw, P.; Colombo, A.; Fyles, A.; Baron, M.H.; Kitchener, H.C.; Nijman, H.W.; Kruitwagen, R.F.; Nout, R.A.; Verhoeven-Adema, K.W.; Smit, V.T.; Putter, H.; Creutzberg, C.L.
2016-01-01
BACKGROUND: About 15% of patients with endometrial cancer have high-risk features and are at increased risk of distant metastases and endometrial cancer-related death. We designed the PORTEC-3 trial to investigate the benefit of adjuvant chemoradiotherapy compared with radiotherapy alone for women
Metformin Use and Endometrial Cancer Survival
Nevadunsky, Nicole S.; Van Arsdale, Anne; Strickler, Howard D.; Moadel, Alyson; Kaur, Gurpreet; Frimer, Marina; Conroy, Erin; Goldberg, Gary L.; Einstein, Mark H.
2013-01-01
Objective Impaired glucose tolerance and diabetes are risk factors for the development of uterine cancer. Although greater progression free survival among diabetic patients with ovarian and breast cancer using metformin have been reported, no studies have assessed the association of metformin use with survival in women with endometrial cancer (EC). Methods We conducted a single-institution retrospective cohort study of all patients treated for uterine cancer from January 1999 through December 2009. Demographic, medical, social, and survival data were abstracted from medical records and the national death registry. Overall survival (OS) was estimated using Kaplan-Meier methods. Cox models were utilized for multivariate analysis. All statistical tests were two-sided. Results Of 985 patients, 114 (12%) had diabetes and were treated with metformin, 136 (14%) were diabetic but did not use metformin, and 735 (74%) had not been diagnosed with diabetes. Greater OS was observed in diabetics with non-endometrioid EC who used metformin than in diabetic cases not using metformin and non-endometrioid EC cases without diabetes (log rank test (p=0.02)). This association remained significant (hazard ratio = 0.54, 95% CI: 0.30–0.97, p<0.04) after adjusting for age, clinical stage, grade, chemotherapy treatment, radiation treatment and presence of hyperlipidemia in multivariate analysis. No association between metformin use and OS in diabetics with endometrioid histology was observed. Conclusion Diabetic EC patients with non-endometrioid tumors who used metformin had lower risk of death than women with EC who did not use metformin. These data suggest that metformin might be useful as adjuvant therapy for non-endometrioid EC. PMID:24189334
DEFF Research Database (Denmark)
Robinson, Kirstine M; Christensen, Karl Bang; Ottesen, Bent
2012-01-01
This study investigates the association between diagnostic delay (total delay), quality of life (QoL) and patient satisfaction, and the associations between QoL and patient satisfaction scores and survival for women diagnosed with ovarian or endometrial cancer....
De Boer, Stephanie M.; Nout, Remi A.; Jurgenliemk-Schulz, Ina M.; Jobsen, Jan J; Lutgens, Ludy C.H.W.; Van Der Steen-Banasik, Elzbieta M.; Mens, Jan Willem M.; Slot, Annerie; Stenfert Kroese, Marika C.; Oerlemans, Simone; Putter, Hein; Verhoeven-Adema, Karen W.; Nijman, Hans W; Creutzberg, Carien L.
2015-01-01
Purpose: To evaluate the long-term health-related quality of life (HRQL) after external beam radiation therapy (EBRT) or vaginal brachytherapy (VBT) among PORTEC-2 trial patients, evaluate long-term bowel and bladder symptoms, and assess the impact of cancer on these endometrial cancer (EC)
de Boer, Stephanie M.; Nout, Remi A.; Jurgenliemk-Schulz, Ina M.; Jobsen, Jan J.; Lutgens, Ludy C. H. W.; van der Steen-Banasik, Elzbieta M.; Mens, Jan Willem M.; Slot, Annerie; Kroese, Marika C. Stenfert; Oerlemans, Simone; Putter, Hein; Verhoeven-Adema, Karen W.; Nijman, Hans W.; Creutzberg, Carien L.
2015-01-01
Purpose To evaluate the long-term health-related quality of life (HRQL) after external beam radiation therapy (EBRT) or vaginal brachytherapy (VBT) among PORTEC-2 trial patients, evaluate long-term bowel and bladder symptoms, and assess the impact of cancer on these endometrial cancer (EC)
de Boer, Stephanie M.; Nout, Remi A.; Jurgenliemk-Schulz, Ina M.; Jobsen, Jan J.; Lutgens, Ludy C. H. W.; van der Steen-Banasik, Elzbieta M.; Mens, Jan Willem M.; Slot, Annerie; Kroese, Marika C. Stenfert; Oerlemans, Simone; Putter, Hein; Verhoeven-Adema, Karen W.; Nijman, Hans W.; Creutzberg, Carien L.
2015-01-01
Purpose: To evaluate the long-term health-related quality of life (HRQL) after external beam radiation therapy (EBRT) or vaginal brachytherapy (VBT) among PORTEC-2 trial patients, evaluate long-term bowel and bladder symptoms, and assess the impact of cancer on these endometrial cancer (EC)
Ko, Emily M; Havrilesky, Laura J; Alvarez, Ronald D; Zivanovic, Oliver; Boyd, Leslie R; Jewell, Elizabeth L; Timmins, Patrick F; Gibb, Randall S; Jhingran, Anuja; Cohn, David E; Dowdy, Sean C; Powell, Matthew A; Chalas, Eva; Huang, Yongmei; Rathbun, Jill; Wright, Jason D
2018-05-01
Health care in the United States is in the midst of a significant transformation from a "fee for service" to a "fee for value" based model. The Medicare Access and CHIP Reauthorization Act of 2015 has only accelerated this transition. Anticipating these reforms, the Society of Gynecologic Oncology developed the Future of Physician Payment Reform Task Force (PPRTF) in 2015 to develop strategies to ensure fair value based reimbursement policies for gynecologic cancer care. The PPRTF elected as a first task to develop an Alternative Payment Model for thesurgical management of low risk endometrial cancer. The history, rationale, and conceptual framework for the development of an Endometrial Cancer Alternative Payment Model are described in this white paper, as well as directions forfuture efforts. Copyright © 2018 Elsevier Inc. All rights reserved.
Endometrial cancer survivors' assessment of the benefits of exercise.
Lukowski, Jessica; Gil, Karen M; Jenison, Eric; Hopkins, Michael; Basen-Engquist, Karen
2012-03-01
The majority of women who have had endometrial cancer remain at risk for obesity related diseases. The social cognitive theory was used to explore their beliefs about exercise to aid in the development of effective interventions. Women who had been treated for Stage I endometrial cancer were asked about their level of exercise to determine if they had been exercising regularly for more than 6 months (exercisers vs non-exercisers). They were asked to rate the likelihood that exercise would result in various health outcomes (expectations) and to rate the importance of these outcomes (expectancies). Scores for how likely exercise would result in an outcome of importance were calculated. Height and weight were obtained from nurses for calculation of BMI. Statistics were conducted using SPSS v 15. There were 106 valid questionnaires (86% participation rate); 41% were exercisers. Mean BMI was significantly lower in exercisers (31.6 ± 1.2 vs. 37.3 ± 1.2, p=0.001); a significantly greater proportion reported not having diabetes, heart disease or hypertension (69.8% vs. 49.2%, p=0.035). Exercisers were significantly more likely to report that feeling better physically and emotionally versus reducing the risk of diseases were likely and important outcomes of exercise (18.2 ± 0.8 vs 15.0 ± 1.0, p=0.002). Exercisers identified outcomes of exercise that are more immediate and subjective as being important and likely outcomes of exercise. Focusing on these aspects of exercise (feeling better physically and emotionally) may aid in the development of effective interventions for non-exercisers. Copyright © 2011. Published by Elsevier Inc.
Yıldırım, Malik Ejder; Karakuş, Savas; Kurtulgan, Hande Küçük; Kılıçgün, Hasan; Erşan, Serpil; Bakır, Sevtap
2017-08-01
Plasminogen activator inhibitor type 1 (PAI-1) is a serine protease inhibitor (Serpine 1), and it inhibits both tissue plasminogen activator and urokinase plasminogen activator which are important in fibrinolysis. We aimed to find whether there is a possible association between PAI-1 level, PAI-1 4G/5G polymorphism, and endometrial cancer. PAI-1 levels in peripheral blood were determined in 82 patients with endometrial carcinoma and 76 female healthy controls using an enzyme-linked immunoassay (ELISA). Then, the genomic DNA was extracted and screened by reverse hybridization procedure (Strip assay) to detect PAI 1 4G/5G polymorphism. The levels of PAI-1 in the patients were higher statistically in comparison to controls (P 5G polymorphism was quite different between patients and controls (P = 0.008), and 4G allelic frequency was significantly higher in the patients of endometrial cancer than in controls (P = 0.026). We found significant difference between Grade 1 and Grade 2+3 patients in terms of the PAI-1 levels (P = 0.047). There was no association between PAI-1 4G/5G polymorphism and the grades of endometrial cancer (P = 0.993). Our data suggest that the level of PAI-1 and PAI-1 4G/5G gene polymorphism are effective in the formation of endometrial cancer. PAI-1 levels are also associated with the grades of endometrial cancer.
Analysis of abnormally thickened endometrial patterns on transvaginal sonography
International Nuclear Information System (INIS)
Lee, Myung Sook; Cho, Hyeun Cha
1999-01-01
To determine whether the transvaginal sonographic appearance of the thickened endometrium can help to predict the underlying endometrial pathologic process. The sonogram reports of fall 41 pre- and 21 postmenopausal women who underwent transvaginal sonogram were retrospectively analyzed. The women undergoing estrogen replacement therapy, tamoxifen therapy or having abnormal cervical cytology were excluded from this study. The analysis of sonographic and histologic results was performed in all patients. Three distinct sonographic patterns were encountered. Type I consisted of heterogeneous endometrial thickening with internal hypoechoic areas (normal [n=4], polyp [n=1] and cancer [n=4] in premenopausal women and cancer [n=4] in postmenopausal women). Type II consisted of echogenic endometrial thickening with or without tiny cysts (normal[n=5], and hyperplasia [n=7] in premenopausal women and normal [n=4], polyp [n=2], and hyperplasia [n=1] in postmenopausal women). Type III consisted of localized well defined endoluminal lesion (normal [n=1], polyp [n=14], hyperplasia [n=1], cancer [n=1], and submucosal mass [n=3] in premenopausal women and normal [n=4], polyp [n=2],submucosal mass [n=3], and hematoma [n=1] in postmenopausal women). The measurement of the endometrial thickness combined with analysis of sonographic echo patterns may be helpful in prediction and differentiation of endometrial disease in pre- and postmenopausal women. Also it can contribute to avoiding unnecessary D and C.
Lin-Hurtubise, Kevin M; Yheulon, Christopher G; Gagliano, Ronald A; Lynch, Henry T
2013-12-01
The lynch syndrome (LS) tumor spectrum involves colorectal cancer (CRC), endometrial cancer (EC), and less frequently various extracolonic non-endometrial cancers (non-EC). The organ-specific survival rates of these patients are well defined, however, the collective survival of all-cancers combined (CRC + EC + non-EC) are unclear. Fifty-two MSH2 patients and 68 MLH1 patients were followed for a median of 6.3 years after diagnosis of first cancer, regardless of type. The proportions of CRC only, EC, non-EC, and multiple primary cancers were compared between the two genotypes. Kaplan-Meier curves were developed for survival comparisons. MSH2 patients present less frequently with only CRC (37% MSH2, 62% MLH1, P = 0.0096), manifest more multiple primary cancers (38% MSH2, 18% MLH1, P = 0.013), develop more extracolonic cancers (62% MSH2, 38% MLH1, P = 0.003), non-EC only cancers (46% MSH2, 24% MLH1, P = 0.028) and carry a greater risk for urinary tract cancer (UTC) (13.4% MSH2, 1.5% MLH1, P = 0.024). There was no difference in 10-year survival between the two groups (P = 0.4). The additional propensity for UTC in MSH2 carriers argues in favor of UTC screening in MSH2 individuals. Other types of cancer screening should be tailored to the expression history of the specific LS mutation. © 2013 Wiley Periodicals, Inc.
De Vivo, Immaculata; Huggins, Gordon S; Hankinson, Susan E; Lescault, Pamela J; Boezen, Hendrika; Colditz, Graham A; Hunter, David J
2002-01-01
Excessive estrogen stimulation unopposed by progesterone strongly predisposes to endometrial cancer. Because the antiproliferative effect of progesterone requires the progesterone receptor (PR), which exists in two isoforms, PR-A and -B, we reasoned that variants in the PR gene may predispose to
L1CAM in Early-Stage Type I Endometrial Cancer: Results of a Large Multicenter Evaluation
Zeimet, A.G.; Reimer, D.; Huszar, M.; Winterhoff, B.; Puistola, U.; Azim, S.A.; Muller-Holzner, E.; Ben-Arie, A.; Kempen, L.C.L.T. van; Petru, E.; Jahn, S.; Geels, Y.P.; Massuger, L.F.A.G.; Amant, F.; Polterauer, S.; Lappi-Blanco, E.; Bulten, J.; Meuter, A.; Tanouye, S.; Oppelt, P.; Stroh-Weigert, M.; Reinthaller, A.; Mariani, A.; Hackl, W.; Netzer, M.; Schirmer, U.; Vergote, I.; Altevogt, P.; Marth, C.; Fogel, M.
2013-01-01
BACKGROUND: Despite the excellent prognosis of Federation Internationale de Gynecologie et d'Obstetrique (FIGO) stage I, type I endometrial cancers, a substantial number of patients experience recurrence and die from this disease. We analyzed the value of immunohistochemical L1CAM determination to
Gaber, Charles; Meza, Rafael; Ruterbusch, Julie J; Cote, Michele L
2016-10-17
The aim of this study is to explore incidence and incidence-based mortality trends for endometrial cancer in the USA and project future incident cases, accounting for differences by race and histological subtype. Data on age-adjusted and age-specific incidence and mortality rates of endometrial cancer were obtained from the Surveillance, Epidemiology, and End Results 18 registries. Trends in rates were analyzed using Joinpoint regression, and average annual percent change (AAPC) in recent years (2006-2011) was computed for histological subtypes by race. Age, histological, and race-specific rates were applied to US Census Bureau population census estimates to project new cases from 2015 to 2040, accounting for observed AAPC trends, which were progressively attenuated for the future years. The annual number of cases is projected to increase substantially from 2015 to 2040 across all racial groups. Considerable variation in incidence and mortality trends was observed both between and within racial groups when considering histology. As the US population undergoes demographic changes, incidence of endometrial cancer is projected to rise. The increase will occur in all racial groups, but larger increases will be seen in aggressive histology subtypes that disproportionately affect black women.
Total laparoscopic radical hysterectomy with pelvic lymphadenectomy for endometrial cancer.
Vasilescu, C; Stănciulea, Oana; Popa, Monica; Anghel, Rodica; Herlea, V; Florescu, Arleziana
2008-01-01
The surgical treatment of endometrial cancer is still a matter of debate. Two of the most controversial issues are the beneficial effect of lymphadenectomy and the feasibility of laparoscopy. The aim of the case report was to describe the feasibility of total laparoscopic radical hysterectomy with pelvic lymphadenectomy in a 56-years-old Caucasian woman diagnosed with endometrial cancer. After a CO2 pneumoperitoneum was created the peritoneum was incised cranially to the para-colic fossa just above the external iliac vessels until the psoas muscle is visualized. The external iliac vessels were identified and lymph nodes from the anterior and the medial surface were removed until the iliac bifurcation and placed in an Endo-bag. The procedure continued with the identification of the hypo-gastric and the umbilical artery which were pulled medially in order to open the obturator fossa and remove the lymphatic tissue superior to the obturator nerve. The next step was the opening of the para-vesical and pararectal spaces by using blunt dissection; this maneuver was facilitated by pulling the uterine fundus towards the opposite direction with the uterine manipulator. The parametrium being isolated between the two spaces can be safely divided. At the superior limit of the parametrium the uterine artery is identified and divided at its origin. Thereafter, by placing the uterine fundus in median and posterior position, the vesicouterine peritoneal fold was opened by scissors and a bladder dissection from the low uterine segment down to the vagina was performed. Then the ureter is dissected, freed from its attachments to the parametria and de-crossed from the uterine artery down to its entry into the bladder. Next the rectovaginal space is opened and the utero-sacral ligaments divided; this allows the division of para-vaginal attachments. The vagina is sectioned and the specimen is extracted transvaginally. Then the vaginal stump was sutured by laparoscopy. Total laparoscopic
18F-FDG-PET/CT in Endometrial Carcinoma
International Nuclear Information System (INIS)
Jeon, Tae Joo
2008-01-01
Endometrial carcinoma is one of the most common gynecologic malignancies and which is predominant in postmenopausal women. Clinically many patients are hospitalized in early stage due to clinical sign and symptom such as vaginal bleeding and in this case, patient's prognosis is known to be good. However, considerable number of patients with advanced and relapsed disease reveal poor prognosis. Therefore, exact staging work up is essential for proper treatment as is primary lesion detection. 18 F-FDG-PET has been widely used for the evaluation of gynecologic malignancies such as cervical carcinoma and ovarian cancer. In contrast, FDG PET application to endometrial carcinoma is limited until now and there is no sufficient data to validate the usefulness of FDG PET for this disease yet. However, several studies showed promising results that FDG PET is sensitive and specific in detection of recurrent or metastatic lesions. Therefore further active investigation in this field can facilitate the use of FDG PET for endometrial carcinoma
International Nuclear Information System (INIS)
Greven, Kathryn M.; D'Agostino, Ralph B.; Lanciano, Rachelle M.; Corn, Benjamin W.
1998-01-01
Purpose/Objective: Many patients who have uterine-confined endometrial cancer with prognostic factors predictive of recurrence are treated with adjuvant pelvic radiation. The addition of a brachytherapy vaginal cuff boost is controversial. Materials and Methods: Between 1983 and 1993, 270 patients received adjuvant postoperative pelvic irradiation following hysterectomy for Stage I or II endometrial cancer. Group A includes 173 patients who received external beam irradiation alone (EBRT), while group B includes 97 patients who received EBRT with a vaginal brachytherapy application. The median dose of EBRT was 45 Gy. Vaginal brachytherapy consisted of a low dose rate ovoid or cylinder in 41 patients, a high dose rate cylinder in 54 patients, and a radioactive gold seed implant in two patients. The median follow-up time was 64 months. The two groups were compared in terms of age, histologic grade, favorable versus unfavorable histology, capillary space invasion, depth of myometrial invasion, and pathologic stage. Results: Chi-square analysis revealed that the only difference between the two groups was the presence of more Stage II patients in group B (38% versus 14%). No difference was detected for 5 year pelvic control and disease-free survival rates between groups A and B. Conclusion: There is no suggestion that the addition of a vaginal cuff brachytherapy boost to pelvic radiation is beneficial for pelvic control or disease-free survival for patients with Stage I or II endometrial cancer. Prospective randomized trials designed to study external irradiation alone versus external beam treatment plus vaginal brachytherapy are unlikely to show a positive result. Because EBRT provides excellent pelvic control, protocol development for uterine-confined corpus cancer should focus on identifying patients at risk for recurrence as well as other means of augmenting EBRT (e.g. addition of chemotherapy) in order to improve disease free survival in those subgroups
2017-01-01
Objective To compare the diagnostic accuracy of transvaginal ultrasound (TVS) and magnetic resonance imaging (MRI) for detecting myometrial infiltration (MI) in endometrial carcinoma. Methods An extensive search of papers comparing TVS and MRI in assessing MI in endometrial cancer was performed in MEDLINE (PubMed), Web of Science, and Cochrane Database from January 1989 to January 2017. Quality was assessed using Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Results Our extended search identified 747 citations but after exclusions we finally included in the meta-analysis 8 articles. The risk of bias for most studies was low for most 4 domains assessed in QUADAS-2. Overall, pooled estimated sensitivity and specificity for diagnosing deep MI were 75% (95% confidence interval [CI]=67%–82%) and 82% (95% CI=75%–93%) for TVS, and 83% (95% CI=76%–89%) and 82% (95% CI=72%–89%) for MRI, respectively. No statistical differences were found when comparing both methods (p=0.314). Heterogeneity was low for sensitivity and high for specificity for TVS and MRI. Conclusion MRI showed a better sensitivity than TVS for detecting deep MI in women with endometrial cancer. However, the difference observed was not statistically significant. PMID:29027404
Bregar, Amy J; Alejandro Rauh-Hain, J; Spencer, Ryan; Clemmer, Joel T; Schorge, John O; Rice, Laurel W; Del Carmen, Marcela G
2017-04-01
To examine patterns of care and survival for Hispanic women compared to white and African American women with high-grade endometrial cancer. We utilized the National Cancer Data Base (NCDB) to identify women diagnosed with uterine grade 3 endometrioid adenocarcinoma, carcinosarcoma, clear cell carcinoma and papillary serous carcinoma between 2003 and 2011. The effect of treatment on survival was analyzed using the Kaplan-Meier method. Factors predictive of outcome were compared using the Cox proportional hazards model. 43,950 women were eligible. African American and Hispanic women had higher rates of stage III and IV disease compared to white women (36.5% vs. 36% vs. 33.5%, p<0.001). African American women were less likely to undergo surgical treatment for their cancer (85.2% vs. 89.8% vs. 87.5%, p<0.001) and were more likely to receive chemotherapy (36.8% vs. 32.4% vs. 32%, p<0.001) compared to white and Hispanic women. Over the entire study period, after adjusting for age, time period of diagnosis, region of the country, urban or rural setting, treating facility type, socioeconomic status, education, insurance, comorbidity index, pathologic stage, histology, lymphadenectomy and adjuvant treatment, African American women had lower overall survival compared to white women (Hazard Ratio 1.21, 95% CI 1.16-1.26). Conversely, Hispanic women had improved overall survival compared to white women after controlling for the aforementioned factors (HR 0.87, 95% CI 0.80-0.93). Among women with high-grade endometrial cancer, African American women have lower all-cause survival while Hispanic women have higher all-cause survival compared to white women after controlling for treatment, sociodemographic, comorbidity and histopathologic variables. Copyright © 2017 Elsevier Inc. All rights reserved.
Clinical significance of inadequate endometrial biopsies prior to hysterectomy.
Turney, Emily H; Farghaly, Hanan; Eskew, Ashley M; Parker, Lynn P; Milam, Michael R
2012-01-01
To evaluate preoperative clinical risk factors associated with significant uterine histopathologic abnormalities in final hysterectomy specimens in patients with inadequate preoperative endometrial biopsies. This is an institutional review board-approved, retrospective cohort analysis of 469 consecutive patients who underwent preoperative endometrial biopsies with subsequent hysterectomy from January 1, 2005, to December 31, 2009, at the University of Louisville Medical Center. We analyzed risk factors for inadequate biopsy and for final diagnosis of endometrial pathology (defined as endometrial hyperplasia or uterine cancer). Of the 469 preoperative endometrial biopsies reviewed, 26.2% (123/469) were inadequate (IBx) and 73.8% (346/469) were adequate and benign. IBx on endometrial biopsies was associated with a greater risk of having significant uterine histopathologic abnormalities on final hysterectomy specimens (6.5% vs. 2.3%, RR 2.8 [95% CI 1.1-7.3], p = 0.04). Although inadequate endometrial biopsies are a common finding, they can be associated with significant uterine histopathologic abnormalities on final hysterectomy specimens.
High dose rate brachytherapy for medically inoperable stage I endometrial cancer
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Petereit, Daniel G; Sarkaria, Jann N; Schink, Julian; Springman, Scott R; Kinsella, Timothy J; Buchler, Dolores A
1995-07-01
Purpose/Objective: To determine the efficacy of high dose rate (HDR) brachytherapy in patients with medically inoperable endometrial cancer clinically confined to the corpus. Materials and Methods: Forty-two patients with endometrial cancer and an intact uterus have been treated since 1989 with HDR brachytherapy. Twenty-six patients with medically inoperable Stage I disease were treated with radiation alone and form the basis of this study. Obesity was assessed using the body mass index (BMI kg/m{sup 2}) scale. Patients with a BMI above 28 were considered obese and those above 35 morbidly obese, per standard anesthesia guidelines. Brachytherapy was delivered in 5 HDR insertions, 1 week apart, without any external beam radiation. The following doses were delivered per insertion: 5.7 Gy to point S, 7.0 Gy to point W, 8.2 Gy to the vaginal surface and 9.2 Gy to point M. Point M represents the conventional point A dose, while points S and W are myometrial points. A single tandem with either ovoids or cylinders was placed, unless the uterine cavity would accommodate 2 tandems. All treatments were outpatient using intravenous fentanyl and midazolam for sedation. Pelvic ultrasound was commonly used at the time of brachytherapy to verify tandem placement. Three year clinical endpoints were calculated using the Kaplan Meier method. Results: The median follow-up for the study cohort was 21 months with follow-up greater than 36 months in 11 patients. Seventeen of the 26 patients were inoperable due to morbid obesity (median weight and BMI; 316 lbs and 55 kg/m{sup 2}, respectively); the other patients had poor cardiopulmonary reserve {+-} obesity. The median age, KPS (Karnofsky Performance Status), weight, ASA (American Society of Anesthesiologists' Physical Class System) and BMI were 63 yrs, 80%, 285 lbs, 3 and 49 kg/m{sup 2}, respectively. Two patients with an ASA of 3 and 4 died from acute cardio-pulmonary events within 30 days of the last insertion, emphasizing the need
High dose rate brachytherapy for medically inoperable stage I endometrial cancer
International Nuclear Information System (INIS)
Petereit, Daniel G.; Sarkaria, Jann N.; Schink, Julian; Springman, Scott R.; Kinsella, Timothy J.; Buchler, Dolores A.
1995-01-01
Purpose/Objective: To determine the efficacy of high dose rate (HDR) brachytherapy in patients with medically inoperable endometrial cancer clinically confined to the corpus. Materials and Methods: Forty-two patients with endometrial cancer and an intact uterus have been treated since 1989 with HDR brachytherapy. Twenty-six patients with medically inoperable Stage I disease were treated with radiation alone and form the basis of this study. Obesity was assessed using the body mass index (BMI kg/m 2 ) scale. Patients with a BMI above 28 were considered obese and those above 35 morbidly obese, per standard anesthesia guidelines. Brachytherapy was delivered in 5 HDR insertions, 1 week apart, without any external beam radiation. The following doses were delivered per insertion: 5.7 Gy to point S, 7.0 Gy to point W, 8.2 Gy to the vaginal surface and 9.2 Gy to point M. Point M represents the conventional point A dose, while points S and W are myometrial points. A single tandem with either ovoids or cylinders was placed, unless the uterine cavity would accommodate 2 tandems. All treatments were outpatient using intravenous fentanyl and midazolam for sedation. Pelvic ultrasound was commonly used at the time of brachytherapy to verify tandem placement. Three year clinical endpoints were calculated using the Kaplan Meier method. Results: The median follow-up for the study cohort was 21 months with follow-up greater than 36 months in 11 patients. Seventeen of the 26 patients were inoperable due to morbid obesity (median weight and BMI; 316 lbs and 55 kg/m 2 , respectively); the other patients had poor cardiopulmonary reserve ± obesity. The median age, KPS (Karnofsky Performance Status), weight, ASA (American Society of Anesthesiologists' Physical Class System) and BMI were 63 yrs, 80%, 285 lbs, 3 and 49 kg/m 2 , respectively. Two patients with an ASA of 3 and 4 died from acute cardio-pulmonary events within 30 days of the last insertion, emphasizing the need for accurate pre
International Nuclear Information System (INIS)
Nagar, Himanshu; Boothe, Dustin; Parikh, Amar; Yondorf, Menachem; Parashar, Bhupesh; Gupta, Divya; Holcomb, Kevin; Caputo, Thomas; Chao, K. S. Clifford; Nori, Dattatreyudu; Wernicke, A. Gabriella
2013-01-01
Purpose: To evaluate the tolerability and toxicity of administering vaginal brachytherapy (VB) concurrently during chemotherapy compared with the sequential approach for patients with endometrial cancer. Methods and Materials: A retrospective analysis of 372 surgically staged patients with endometrial cancer American Joint Committee on Cancer 2009 stages I to IV treated with adjuvant postoperative radiation therapy (RT) at our institution from 2001 to 2012 was conducted. All patients received VB + external beam RT (EBRT) + 6 cycles of adjuvant carboplatin- and paclitaxel-based chemotherapy. The VB mean dose was 15.08 Gy (range, 15-20 Gy), with 3 to 4 weekly applications, and the EBRT mean dose was 45 Gy delivered with 3-dimensional or intensity modulated RT techniques. Hematologic, gastrointestinal (GI), and genitourinary (GU) toxicities were assessed by Common Toxicity Criteria (CTC) and compared between sequential and concurrent chemotherapy and VB schedules. Results: Among patients who received RT and adjuvant chemotherapy, 180 of 372 patients (48%) received RT sandwiched between cycles 3 and 4 of chemotherapy. A separate group of 192 patients (52%) were treated with VB during the first 3 cycles of chemotherapy, with a weekly application on nonchemotherapy days, and received the EBRT portion in a sandwiched fashion. Patients treated with VB during chemotherapy had a decreased overall treatment time by 4 weeks (P .05). CTC grade 3 or 4 hematologic, GI, and GU toxicities were zero. Conclusions: VB during chemotherapy is well tolerated, decreases overall treatment time, and does not render more toxicity than the sequential regimen
Endometrial Carcinoma in a 26-Year-Old Patient with Bardet-Biedl Syndrome
Directory of Open Access Journals (Sweden)
Olga Grechukhina
2018-01-01
Full Text Available Background. Bardet-Biedl Syndrome (BBS is a rare genetic condition characterized by cognitive impairment, dysmorphism, central obesity, and diabetes mellitus, among other abnormalities. Although some of these characteristics are known independent risk factors for endometrial cancer and its precursors, the association between BBS and endometrial cancer is underreported. Case. We present the case of a 26-year-old patient with BBS and clinical signs of hyperestrogenism who presented with abnormal uterine bleeding and was diagnosed with endometrioid adenocarcinoma. She ultimately underwent definitive surgical treatment with hysterectomy and bilateral salpingectomy. Conclusions. This is one of only a few reports in the literature describing the association of BBS and endometrioid endometrial adenocarcinoma. Given the association of BBS with risk factors for hyperestrogenism such as truncal obesity, hyperinsulinemia, and ovulatory dysfunction, providers should have increased suspicion for endometrial cancer in young patients with BBS and abnormal uterine bleeding.
Hu, Yi-Cheng; Wu, Chien-Tung; Lai, Jung-Nien; Tsai, Yueh-Ting
2015-07-01
Tamoxifen users sometimes seek complementary and alternative medicine advice for treatment of a variety of illness and co-administer with phytoestrogen-containing herbs, resulting in an increasing concern of its influence in subsequent endometrial cancer risk. Our study aims to determine the prevalence of Chinese herbal products containing coumestrol, genistein, or daidzein and their association with subsequent endometrial cancer risk among tamoxifen-treated breast cancer survivors in Taiwan. We selected all patients who were newly diagnosed with invasive breast cancer and received tamoxifen treatment between January 1, 1998, and December 31, 2008, from the National Health Insurance Research Database. Among the 26,656 tamoxifen-treated breast cancer survivors, we evaluated the usage, frequency of service, and prescription of Chinese herbal products containing coumestrol, genistein, or daidzein. The logistic regression method was employed to calculate the odds ratios for utilization of those herbal products. Cox proportional hazard regression was set to calculate the hazard ratios of endometrial cancer associated with such usage. Of the patients surveyed, 36.2% (n=9652) of the tamoxifen-treated breast cancer survivors examined in the study had consumed Chinese herbal products containing coumestrol, genistein, or daidzein during the study period. Exposure to Ge Gen(Puerariae Radix) specifically was the most extensive. For it, the population consumed an average cumulative dose of above 180g. Compared to those who had never used Chinese herbal products, breast cancer survivors who had taken Chinese herbal products containing coumestrol, genistein, or daidzein concurrently with tamoxifen treatment did not have a higher hazard ratio for subsequent development of endometrial cancer. Among those tamoxifen-treated female breast cancer survivors in Taiwan, consumption of Chinese herbal products containing coumestrol, genistein, or daidzein is negatively correlated with
Mautone, Daniele; Dall'asta, Andrea; Monica, Michela; Galli, Letizia; Capozzi, Vito Andrea; Marchesi, Federico; Giordano, Giovanna; Berretta, Roberto
2016-07-01
Port-site metastases (PSMs) are well-known potential complications of laparoscopic surgery for gynaecologic malignancies. The present case study reports PSM following laparoscopic surgery for Stage IA Grade 1 endometrioid endometrial cancer (EEC). The recurrence developed within 7 months following primary surgery and required surgical excision followed by adjuvant chemo-radio therapy. After 9 months, the patient remains disease-free. PSMs are rare complications following laparoscopic surgery. Amongst the 23 cases of endometrial cancer PSMs reported so far, only 4 followed EEC Stage IA Grade 1-2. The present study reports a rare case of PSM after Stage IA Grade 1 EEC. The clinical and prognostic relevance of PSMs has not been identified so far; and it is not known whether PSMs represent a local recurrence or a systemic recurrence. Surgeons should be aware that even low-risk EEC may be followed by PSMs and should take steps to prevent these rare recurrences.
Directory of Open Access Journals (Sweden)
Bingyi Yang
Full Text Available We aimed to evaluate the value of immunohistochemical markers and serum CA125 in predicting the risk of lymph node metastasis (LNM in women with endometrial cancer and to identify a low-risk group of LNM. The medical records of 370 patients with endometrial endometrioid adenocarcinoma who underwent surgical staging in the Obstetrics & Gynecology Hospital of Fudan University were collected and retrospectively reviewed. Immunohistochemical markers were screened. A model using serum cancer antigen 125 (CA125 level, the immunohistochemical markers progesterone receptor (PR and Ki67 was created for prediction of LNM. A predicted probability of 4% among these patients was defined as low risk. The developed model was externally validated in 200 patients from Shanghai Cancer Center. The efficiency of the model was compared with three other reported prediction models. Patients with serum CA125 50% and Ki67 < 40% in cancer lesion were defined as low risk for LNM. The model showed good discrimination with an area under the receiver operating characteristic curve of 0.82. The model classified 61.9% (229/370 of patients as being at low risk for LNM. Among these 229 patients, 6 patients (2.6% had LNM and the negative predictive value was 97.4% (223/229. The sensitivity and specificity of the model were 84.6% and 67.4% respectively. In the validation cohort, the model classified 59.5% (119/200 of patients as low-risk, 3 out of these 119 patients (2.5% has LNM. Our model showed a predictive power similar to those of two previously reported prediction models. The prediction model using serum CA125 and the immunohistochemical markers PR and Ki67 is useful to predict patients with a low risk of LNM and has the potential to provide valuable guidance to clinicians in the treatment of patients with endometrioid endometrial cancer.
Mitsuhashi, A; Sato, Y; Kiyokawa, T; Koshizaka, M; Hanaoka, H; Shozu, M
2016-02-01
Metformin, widely used in the treatment of type 2 diabetes mellitus, reduces the risk of cancer and relapse after treatment. Fertility-sparing treatment for endometrial cancer (EC) with progestin is associated with a high chance of disease regression, and the high relapse rate continues to be a problem. We assessed the efficacy of metformin in preventing recurrence after medroxyprogesterone acetate (MPA) as fertility-sparing treatment for atypical endometrial hyperplasia (AEH) and EC. This phase II study enrolled 17 patients with AEH and 19 patients with EC limited to the endometrium (age, 20-40 years). MPA (400 mg/day) and metformin (750-2250 mg/day) were administered for 24-36 weeks to achieve a complete response (CR). Metformin was administered until conception, even after MPA discontinuation. The primary end point was relapse-free survival (RFS) after remission. We analyzed all efficacy end points in the full analysis set. The body mass index was ≥25 kg/m(2) in 27 patients (mean, 31 kg/m(2); range, 19-51 kg/m(2)), and the homeostasis model assessment for insulin resistance index was ≥2.5 in 24 patients (mean, 4.7; range, 0.7-21). Two patients showed progression at 12 weeks [6%; 95% confidence interval (CI) 2-18]. At 36 weeks, 29 (81%; 95% CI 65-90) patients achieved CR, and 5 (14%; 95% CI 6-29) patients achieved partial response. During a median follow-up of 38 months (range, 9-66 months) after remission, relapse was confirmed in three of the patients who had achieved CR (relapse rate, 10%). The 3-year estimated RFS rate was 89%. No patients experienced severe toxicity. Metformin inhibited disease relapse after MPA therapy. The combination of metformin and MPA in EC treatment should be studied further. UMIN 000002210. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
Endometrial cancers occurring 10 or more years after pelvic irradiation for carcinoma
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Rodriguez, J.; Hart, W.R.
1982-01-01
Fifteen patients who developed cancer of the endometrium 10 or more years after pelvic irradiation for carcinoma were selected for study from a group of 64 cases of postirradiation malignant pelvic tumors diagnosed during a 48-year span. The average interval between radiotherapy and diagnosis of the subsequent endometrial cancer was 17.2 years. Irradiation initially had been done for squamous cell carcinoma of the cervix in 13 cases (87%) and for ovarian tumors in two instances. Almost all patients had received megavoltage external radiation combined with radium implants. Two-thirds of the tumors were adenocarcinomas and one-third were carcinosarcomas (either homologous or heterologous). Although the risk of second primary malignant tumors following therapeutic irradiation for pelvic tumors probably is very low, the emergence of new genital tract cancers in long-term survivors must be anticipated, regardless of whether the postirradiation cancers are spontaneous or radiation-induced
Two Cases of Endometrial Cancer in Twin Sisters with Myotonic Dystrophy
Directory of Open Access Journals (Sweden)
Ezra Y. Koh
2016-01-01
Full Text Available We describe two cases of endometrial cancer (EC occurring in nulligravid twin sisters with myotonic dystrophy. Both tested negative for Lynch syndrome and both were treated with laparoscopic hysterectomy with bilateral salpingooophorectomy and adjuvant radiotherapy. Although EC tends to run in families, the diagnosis in itself is not considered sufficient cause for screening or prophylactic measures in close relatives. However, the presence of additional risk factors, such as nulligravidity and myotonic dystrophy in the underlying cases, may call for extra vigilance in first-degree family members.
Directory of Open Access Journals (Sweden)
Stacker Steven A
2010-07-01
Full Text Available Abstract Background It has been hypothesised that increased VEGF-D expression may be an independent prognostic factor for endometrial cancer progression and lymph node metastasis; however, the mechanism by which VEGF-D may promote disease progression in women with endometrial cancer has not been investigated. Our aim was to describe the distribution of lymphatic vessels in mouse uterus and to examine the effect of VEGF-D over-expression on these vessels in a model of endometrial cancer. We hypothesised that VEGF-D over-expression would stimulate growth of new lymphatic vessels into the endometrium, thereby contributing to cancer progression. Methods We initially described the distribution of lymphatic vessels (Lyve-1, podoplanin, VEGFR-3 and VEGF-D expression in the mouse uterus during the estrous cycle, early pregnancy and in response to estradiol-17beta and progesterone using immunohistochemistry. We also examined the effects of VEGF-D over-expression on uterine vasculature by inoculating uterine horns in NOD SCID mice with control or VEGF-D-expressing 293EBNA tumor cells. Results Lymphatic vessels positive for the lymphatic endothelial cell markers Lyve-1, podoplanin and VEGFR-3 profiles were largely restricted to the connective tissue between the myometrial circular and longitudinal muscle layers; very few lymphatic vessel profiles were observed in the endometrium. VEGF-D immunostaining was present in all uterine compartments (epithelium, stroma, myometrium, although expression was generally low. VEGF-D immunoexpression was slightly but significantly higher in estrus relative to diestrus; and in estradiol-17beta treated mice relative to vehicle or progesterone treated mice. The presence of VEGF-D over-expressing tumor cells did not induce endometrial lymphangiogenesis, although changes were observed in existing vessel profiles. For myometrial lymphatic and endometrial blood vessels, the percentage of profiles containing proliferating
Incisional Recurrences After Endometrial Cancer Surgery.
Bogani, Giorgio; Dowdy, Sean C; Cliby, William A; Gostout, Bobbie S; Kumar, Sanjeev; Ghezzi, Fabio; Multinu, Francesco; Mariani, Andrea
2015-11-01
The aim of the present study was to estimate the incisional recurrence (IR) rate after endometrial cancer (EC) staging surgery and analyze characteristics of affected patients. We retrospectively searched for patients with EC at 2 institutions and analyzed the occurrence of IR after open, laparoscopic, or robotic surgery. Additionally, a review of the literature was performed. Out of 2,636 patients with EC, 1,732 (65.7%), 461 (17.5%), and 443 (16.8%) had open, laparoscopic, and robotic surgery, respectively. Only 3 patients (0.11%) had IR, all after open surgery. Additionally, 38 cases of IR were identified from the literature. Patients with non-isolated IR had worse overall survival than patients with isolated IR (p=0.04). Among this latter group, combined treatments may be associated with improved survival outcome. IR after EC surgery is rare and may occur after minimally-invasive or open operations. Combination of local and systemic treatments may provide favorable outcomes for patients with isolated IR. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.
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Chovanec, Josef; Selingerova, Iveta; Greplova, Kristina
2017-01-01
Background: We investigated the efficacy of circulating biomarkers together with histological grade and age to predict deep myometrial invasion (dMI) in endometrial cancer patients. Methods: HE4ren was developed adjusting HE4 serum levels towards decreased glomerular filtration rate as quantified...... levels to reduced eGFR that enables quantification of time-dependent changes in HE4 production and elimination irrespective of age and renal function in women. Utilizing HE4ren improves performance of biomarker-based models for prediction of dMI in endometrial cancer patients....
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Zhang, Hualin, E-mail: hualin.zhang@northwestern.edu; Donnelly, Eric D.; Strauss, Jonathan B. [Department of Radiation Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Northwestern Memorial Hospital, Chicago, Illinois 60611 (United States); Qi, Yujin [Centre for Medical Radiation Physics, University of Wollongong, Wollongong, NSW 2522 (Australia)
2016-01-15
Purpose: To evaluate high-dose-rate (HDR) vaginal cuff brachytherapy (VCBT) in the treatment of endometrial cancer in a cylindrical target volume with either a varied or a constant cancer cell distributions using the linear quadratic (LQ) model. Methods: A Monte Carlo (MC) technique was used to calculate the 3D dose distribution of HDR VCBT over a variety of cylinder diameters and treatment lengths. A treatment planning system (TPS) was used to make plans for the various cylinder diameters, treatment lengths, and prescriptions using the clinical protocol. The dwell times obtained from the TPS were fed into MC. The LQ model was used to evaluate the therapeutic outcome of two brachytherapy regimens prescribed either at 0.5 cm depth (5.5 Gy × 4 fractions) or at the vaginal mucosal surface (8.8 Gy × 4 fractions) for the treatment of endometrial cancer. An experimentally determined endometrial cancer cell distribution, which showed a varied and resembled a half-Gaussian distribution, was used in radiobiology modeling. The equivalent uniform dose (EUD) to cancer cells was calculated for each treatment scenario. The therapeutic ratio (TR) was defined by comparing VCBT with a uniform dose radiotherapy plan in term of normal cell survival at the same level of cancer cell killing. Calculations of clinical impact were run twice assuming two different types of cancer cell density distributions in the cylindrical target volume: (1) a half-Gaussian or (2) a uniform distribution. Results: EUDs were weakly dependent on cylinder size, treatment length, and the prescription depth, but strongly dependent on the cancer cell distribution. TRs were strongly dependent on the cylinder size, treatment length, types of the cancer cell distributions, and the sensitivity of normal tissue. With a half-Gaussian distribution of cancer cells which populated at the vaginal mucosa the most, the EUDs were between 6.9 Gy × 4 and 7.8 Gy × 4, the TRs were in the range from (5.0){sup 4} to (13
Appendectomy with cytoreductive surgery for ovarian and type 2 endometrial carcinoma.
Wong, L F A; Wahab, N A; Gleeson, N
2014-01-01
There is considerable variation within and between cancer centers in the practice of appendectomy as part of cytoreductive surgery for ovarian carcinoma and in the surgical staging of endometrial carcinoma. The purpose of this study was to determine the prevalence and the type of appendiceal pathology, the morbidity associated with appendectomy in gynaecologic cancer surgery. This is a retrospective review of all cytoreductive surgery for ovarian carcinoma and surgical staging for endometrial carcinoma with appendectomy over a four year period. Two hundred and fifty-one patients (38 patients for endometrial carcinoma surgery and 213 patients for ovarian cytoreduction) had an appendectomy performed. Metastases to the appendix was present in 46 (23.2%) of primary ovarian carcinoma and one (2.6%) primary endometrial carcinosarcoma. The appendix was more likely to be involved in advanced stage ovarian cancer with positive peritoneal washings, omental deposits, grade 3 differentiation, and papillary serous histology. Sixteen (6.4%) co-incidental primary appendiceal tumours were detected. No postoperative morbidity specific to appendectomy was identified. One case of ovarian carcinoma was upstaged from IC to IIIA by the appendiceal metastases. There was no upstaging of disease in the endometrial carcinoma group. Appendectomy is an integral part of ovarian cytoreductive surgery but the authors found it did not upstage the disease in a clinically significant manner. The incidence of co-incidental appendiceal primary tumours was high in this series and may add value to the procedure in preventing further surgeries. The absence of procedure related morbidity is reassuring. The authors recommend appendectomy for all ovarian staging surgery and its consideration in type 2 endometrial cancer.
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Bilbao, Cristina; Lara, Pedro Carlos; Ramirez, Raquel; Henriquez-Hernandez, Luis Alberto; Rodriguez, German; Falcon, Orlando; Leon, Laureano; Perucho, Manuel
2010-01-01
Purpose: To elucidate whether microsatellite instability (MSI) predicts clinical outcome in radiation-treated endometrioid endometrial cancer (EEC). Methods and Materials: A consecutive series of 93 patients with EEC treated with extrafascial hysterectomy and postoperative radiotherapy was studied. The median clinical follow-up of patients was 138 months, with a maximum of 232 months. Five quasimonomorphic mononucleotide markers (BAT-25, BAT-26, NR21, NR24, and NR27) were used for MSI classification. Results: Twenty-five patients (22%) were classified as MSI. Both in the whole series and in early stages (I and II), univariate analysis showed a significant association between MSI and poorer 10-year local disease-free survival, disease-free survival, and cancer-specific survival. In multivariate analysis, MSI was excluded from the final regression model in the whole series, but in early stages MSI provided additional significant predictive information independent of traditional prognostic and predictive factors (age, stage, grade, and vascular invasion) for disease-free survival (hazard ratio [HR] 3.25, 95% confidence interval [CI] 1.01-10.49; p = 0.048) and cancer-specific survival (HR 4.20, 95% CI 1.23-14.35; p = 0.022) and was marginally significant for local disease-free survival (HR 3.54, 95% CI 0.93-13.46; p = 0.064). Conclusions: These results suggest that MSI may predict radiotherapy response in early-stage EEC.
Applicator-guided volumetric-modulated arc therapy for low-risk endometrial cancer
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Cilla, Savino, E-mail: savinocilla@gmail.com [Medical Physics Unit, Fondazione di ricerca e cura “Giovanni Paolo II,” Università Cattolica del Sacro Cuore, Campobasso (Italy); Macchia, Gabriella [Radiation Oncology Unit, Fondazione di ricerca e cura “Giovanni Paolo II,” Università Cattolica del Sacro Cuore, Campobasso (Italy); Sabatino, Domenico [Medical Physics Unit, Fondazione di ricerca e cura “Giovanni Paolo II,” Università Cattolica del Sacro Cuore, Campobasso (Italy); Digesù, Cinzia; Deodato, Francesco [Radiation Oncology Unit, Fondazione di ricerca e cura “Giovanni Paolo II,” Università Cattolica del Sacro Cuore, Campobasso (Italy); Piermattei, Angelo [Physics Institute, Università Cattolica del Sacro Cuore, Rome (Italy); De Spirito, Marco [Medical Physics Unit, Fondazione di ricerca e cura “Giovanni Paolo II,” Università Cattolica del Sacro Cuore, Campobasso (Italy); Morganti, Alessio G. [Radiation Oncology Unit, Fondazione di ricerca e cura “Giovanni Paolo II,” Università Cattolica del Sacro Cuore, Campobasso (Italy); Radiation Oncology Unit, Università Cattolica del Sacro Cuore, Rome (Italy)
2013-04-01
The aim of this study was to report the feasibility of volumetric-modulated arc therapy (VMAT) in the postoperative irradiation of the vaginal vault. Moreover, the VMAT technique was compared with 3D conformal radiotherapy (3D-CRT) and fixed-field intensity-modulated radiotherapy (IMRT), in terms of target coverage and organs at risk sparing. The number of monitor units and the delivery time were analyzed to score the treatment efficiency. All plans were verified in a dedicated solid water phantom using a 2D array of ionization chambers. Twelve patients with endometrial carcinoma who underwent radical hystero-adenexectomy and fixed-field IMRT treatments were retrospectively included in this analysis; for each patient, plans were compared in terms of dose-volume histograms, homogeneity index, and conformity indexes. All techniques met the prescription goal for planning target volume coverage, with VMAT showing the highest level of conformity at all dose levels. VMAT resulted in significant reduction of rectal and bladder volumes irradiated at all dose levels compared with 3D-CRT. No significant differences were found with respect to IMRT. Moreover, a significant improvement of the dose conformity was reached by VMAT technique not only at the 95% dose level (0.74 vs. 0.67 and 0.62) but also at 50% and 75% levels of dose prescription. In addition, VMAT plans showed a significant reduction of monitor units by nearly 28% with respect to IMRT, and reduced treatment time from 11 to <3 minutes for a single 6-Gy fraction. In conclusion, VMAT plans can be planned and carried out with high quality and efficiency for the irradiation of vaginal vault alone, providing similar or better sparing of organs at risk to fixed-field IMRT and resulting in the most efficient treatment option. VMAT is currently our standard approach for radiotherapy of low-risk endometrial cancer.
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Antonsen, Sofie Leisby; Jensen, Lisa Neerup; Loft, Annika
2012-01-01
OBJECTIVES: The aim of this prospective multicenter study was to evaluate and compare the diagnostic performance of PET/CT, MRI and transvaginal two-dimensional ultrasound (2DUS) in the preoperative assessment of endometrial cancer (EC). METHODS: 318 consecutive women with EC were included when...
Basen-Engquist, Karen; Carmack, Cindy L; Perkins, Heidi; Hughes, Daniel; Serice, Susan; Scruggs, Stacie; Pinto, Bernardine; Waters, Andrew
2011-01-01
Physical activity has been shown to benefit cancer survivors' physical functioning, emotional well-being, and symptoms. Physical activity may be of particular benefit to survivors of endometrial cancer because they are more likely to be obese and sedentary than the general population, as these are risk factors for the disease, and thus experience a number of related co-morbid health problems. However, there is little research systematically studying mechanisms of physical activity adherence in cancer survivor populations. This paper describes the design of the Steps to Health study, which applies a Social Cognitive Theory-based model of endometrial cancer survivors' adoption and maintenance of exercise in the context of an intervention to increase walking or other moderate intensity cardiovascular activity. In Steps to Health we will test the influence of self-efficacy and outcome expectations on adherence to exercise recommendations, as well as studying the determinants of self-efficacy. Endometrial cancer survivors who are at least 6 months post-treatment are provided with an intervention involving print materials and telephone counseling, and complete assessments of fitness, activity, self-efficacy and outcome expectations, and determinants of self-efficacy every two months for a six month period. In addition to testing an innovative model, the Steps to Health study employs multiple assessment methods, including ecological momentary assessment, implicit tests of cognitive variables, and ambulatory monitoring of physical activity. The study results can be used to develop more effective interventions for increasing physical activity in sedentary cancer survivors by taking into account the full complement of sources of self-efficacy information and outcome expectations.
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Pawel Sadlecki
2014-01-01
Full Text Available Hypoxia-inducible factor-1α (HIF-1α, glucose transporter-1 (GLUT-1, and carbon anhydrase IX (CAIX are important molecules that allow adaptation to hypoxic environments. The aim of our study was to investigate the correlation between HIF-1α, GLUT-1, and CAIX protein level with the clinicopathological features of endometrial cancer patients. Materials and Methods. 92 endometrial cancer patients, aged 37–84, were enrolled to our study. In all patients clinical stage, histologic grade, myometrial invasion, lymph node, and distant metastases were determined. Moreover, the survival time was assessed. Immunohistochemical analyses were performed on archive formalin fixed paraffin embedded tissue sections. Results. High significant differences (P=0.0115 were reported between HIF-1α expression and the histologic subtype of cancer. Higher HIF-1α expression was associated with the higher risk of recurrence (P=0.0434. The results of GLUT-1 and CAIX expression did not reveal any significant differences between the proteins expression in the primary tumor and the clinicopathological features. Conclusion. The important role of HIF-1α in the group of patients with the high risk of recurrence and the negative histologic subtype of the tumor suggest that the expression of this factor might be useful in the panel of accessory pathomorphological tests and could be helpful in establishing more accurate prognosis in endometrial cancer patients.
Haughian, James M.; Reno, Elaine M.; Thorne, Alicia M.; Bradford, Andrew P.
2009-01-01
Endometrial cancer is the most common invasive gynecologic malignancy, yet molecular mechanisms and signaling pathways underlying its etiology and pathophysiology remain poorly characterized. We sought to define a functional role for the protein kinase C (PKC) isoform, PKCα, in an established cell model of endometrial adenocarcinoma. Ishikawa cells depleted of PKCα protein grew slower, formed fewer colonies in anchorage-independent growth assays and exhibited impaired xenograft tumor formation in nude mice. Consistent with impaired growth, PKCα knockdown increased levels of the cyclin dependent kinase (CDK) inhibitors p21Cip1/WAF1 (p21) and p27Kip1 (p27). Despite the absence of functional phosphatase and tensin homologue (PTEN) protein in Ishikawa cells, PKCα knockdown reduced Akt phosphorylation at serine 473 and concomitantly inhibited phosphorylation of the Akt target, glycogen synthase kinase-3β (GSK-3β). PKCα knockdown also resulted in decreased basal ERK phosphorylation and attenuated ERK activation following EGF stimulation. p21 and p27 expression was not increased by treatment of Ishikawa cells with ERK and Akt inhibitors, suggesting PKCα regulates CDK expression independently of Akt and ERK. Immunohistochemical analysis of grade 1 endometrioid adenocarcinoma revealed aberrant PKCα expression, with foci of elevated PKCα staining, not observed in normal endometrium. These studies demonstrate a critical role for PKCα signaling in endometrial tumorigenesis by regulating expression of CDK inhibitors p21 and p27 and activation of Akt and ERK dependent proliferative pathways. Thus, targeting PKCα may provide novel therapeutic options in endometrial tumors. PMID:19672862
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Le, Tien; Menard, Chantal; Samant, Rajiv; Choan, E.; Hopkins, Laura; Faught, Wylam; Fung-Kee-Fung, Michael
2009-01-01
Purpose: Adjuvant radiotherapy (RT) is often considered for endometrial cancer. We studied the effect of RT and surgical treatment on patients' quality of life (QOL). Methods and Materials: All patients referred to the gynecologic oncology clinics with biopsy findings showing endometrial cancer were recruited. QOL assessments were performed using the European Organization for Research and Treatment of Cancer QOL questionnaire-C30, version 3. Assessments were obtained at study entry and at regular 3-month intervals for a maximum of 2 years. Open-ended telephone interviews were done every 6 months. Linear mixed regression models were built using QOL domain scores as dependent variables, with the predictors of surgical treatment and adjuvant RT type. Results: A total of 40 patients were recruited; 80% of the surgeries were performed by laparotomy. Significant improvements were seen in most QOL domains with increased time from treatment. Adjuvant RT resulted in significantly more severe bowel symptoms and improvement in insomnia compared with conservative follow-up. No significant adverse effect from adjuvant RT was seen on the overall QOL. Bowel symptoms were significantly increased in patients treated with laparotomy compared with laparoscopy in the patients treated with whole pelvic RT. Qualitatively, about one-half of the patients noted improvements in their overall QOL during follow-up, with easy fatigability the most prevalent. Conclusion: No significant adverse effect was seen on patients' overall QOL with adjuvant pelvic RT after the recovery period. The acute adverse effects on patients' QOL significantly improved with an increasing interval from diagnosis.
Directory of Open Access Journals (Sweden)
Navya Nair
2016-12-01
Full Text Available Endometrial cancer is the most common gynecologic malignancy, and its incidence and associated mortality are increasing. Despite the immediate need to detect these cancers at an earlier stage, there is no effective screening methodology or protocol for endometrial cancer. The comprehensive, genomics-based analysis of endometrial cancer by The Cancer Genome Atlas (TCGA revealed many of the molecular defects that define this cancer. Based on these cancer genome results, and in a prospective study, we hypothesized that the use of ultra-deep, targeted gene sequencing could detect somatic mutations in uterine lavage fluid obtained from women undergoing hysteroscopy as a means of molecular screening and diagnosis.Uterine lavage and paired blood samples were collected and analyzed from 107 consecutive patients who were undergoing hysteroscopy and curettage for diagnostic evaluation from this single-institution study. The lavage fluid was separated into cellular and acellular fractions by centrifugation. Cellular and cell-free DNA (cfDNA were isolated from each lavage. Two targeted next-generation sequencing (NGS gene panels, one composed of 56 genes and the other of 12 genes, were used for ultra-deep sequencing. To rule out potential NGS-based errors, orthogonal mutation validation was performed using digital PCR and Sanger sequencing. Seven patients were diagnosed with endometrial cancer based on classic histopathologic analysis. Six of these patients had stage IA cancer, and one of these cancers was only detectable as a microscopic focus within a polyp. All seven patients were found to have significant cancer-associated gene mutations in both cell pellet and cfDNA fractions. In the four patients in whom adequate tumor sample was available, all tumor mutations above a specific allele fraction were present in the uterine lavage DNA samples. Mutations originally only detected in lavage fluid fractions were later confirmed to be present in tumor but at
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Lindstroem, G.; Bavel, B. van; Bjoernfoth, H. [MTM Research Centre, Oerebro Univ., Oerebro (Sweden); Hardell, L. [Dept. of Oncology, Univ. Hospital, Oerebro (Sweden)
2004-09-15
Environmental pollutants with hormonal activity, such as xenoestrogens, have for several years been of concern as potential risk factors for hormone dependant tumors. Impacts of increasing levels of xenoestrogens have been observed in aquatic organisms. In humans concern has been focused on ''endocrine disrupting chemicals'' with either estrogenic or antiestrogenic activities. Some persistent organic pollutants (POPs) such as polychlorinated biphenyls (PCBs), and especially the hydroxylated metabolites, and chlordanes, have been postulated to be endocrine disruptors. PCBs have been shown to reverse gonadal sex in turtle5 and abnormalities of reproductive development has been described in juvenile alligators living in contaminated environment in Florida. Hexachlorobenzene (HCB) has been shown to have endocrine-disrupting properties. Also p,p'-dichlorodiphenyl-dichloroethylene (p,p'-DDE) the most persistent metabolite of p,p'-DDT has been postulated to be an environmental endocrine disruptor. In a case-control study on patients with testicular cancer we found higher concentrations of PCBs, HCB and chlordanes in mothers to cases than in mothers to controls. Similar concentrations were found in cases with testicular cancer as in the population controls. The study gave support to the hypothesis that exposure to endocrine disruptors during the fetal period may be of etiologic importance in the etiology of testicular cancer. Another hormone dependent cancer is endometrial cancer. It accounted for 5.8% of all cancers incidents among Swedish women in 2002. The cumulative probability of developing the disease before 85 years of age was 2.8% in 2002. Estrogen replacement has been suggested as a risk factor among several others. The first cases of endometrial cancer among women using estrogen replacement therapy were reported in early 1960's. Is there a relationship between levels of POPs and incidence rate? The aim is to investigate
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Karin Tamm-Rosenstein
Full Text Available BACKGROUND: Estrogen (E2 and progesterone (P4 are key players in the maturation of the human endometrium. The corresponding steroid hormone modulators, tamoxifen (TAM and mifepristone (RU486 are widely used in breast cancer therapy and for contraception purposes, respectively. METHODOLOGY/PRINCIPAL FINDINGS: Gene expression profiling of the human endometrial Ishikawa cancer cell line treated with E2 and P4 for 3 h and 12 h, and TAM and RU486 for 12 h, was performed using RNA-sequencing. High levels of mRNA were detected for genes, including PSAP, ATP5G2, ATP5H, and GNB2L1 following E2 or P4 treatment. A total of 82 biomarkers for endometrial biology were identified among E2 induced genes, and 93 among P4 responsive genes. Identified biomarkers included: EZH2, MDK, MUC1, SLIT2, and IL6ST, which are genes previously associated with endometrial receptivity. Moreover, 98.8% and 98.6% of E2 and P4 responsive genes in Ishikawa cells, respectively, were also detected in two human mid-secretory endometrial biopsy samples. TAM treatment exhibited both antagonistic and agonistic effects of E2, and also regulated a subset of genes independently. The cell cycle regulator cyclin D1 (CCND1 showed significant up-regulation following treatment with TAM. RU486 did not appear to act as a pure antagonist of P4 and a functional analysis of RU486 response identified genes related to adhesion and apoptosis, including down-regulated genes associated with cell-cell contacts and adhesion as CTNND1, JUP, CDH2, IQGAP1, and COL2A1. CONCLUSIONS: Significant changes in gene expression by the Ishikawa cell line were detected after treatments with E2, P4, TAM, and RU486. These transcriptome data provide valuable insight into potential biomarkers related to endometrial receptivity, and also facilitate an understanding of the molecular changes that take place in the endometrium in the early stages of breast cancer treatment and contraception usage.
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Patel, Samir; Portelance, Lorraine; Gilbert, Lucy; Tan, Leonard; Stanimir, Gerald; Duclos, Marie; Souhami, Luis
2007-01-01
Purpose: To retrospectively assess prognostic factors and patterns of recurrence in patients with pathologic Stage III endometrial cancer. Methods and Materials: Between 1989 and 2003, 107 patients with pathologic International Federation of Gynecology and Obstetrics Stage III endometrial adenocarcinoma confined to the pelvis were treated at our institution. Adjuvant radiotherapy (RT) was delivered to 68 patients (64%). The influence of multiple patient- and treatment-related factors on pelvic and distant control and overall survival (OS) was evaluated. Results: Median follow-up for patients at risk was 41 months. Five-year actuarial OS was significantly improved in patients treated with adjuvant RT (68%) compared with those with resection alone (50%; p = 0.029). Age, histology, grade, uterine serosal invasion, adnexal involvement, number of extrauterine sites, and treatment with adjuvant RT predicted for improved survival in univariate analysis. Multivariate analysis revealed that grade, uterine serosal invasion, and treatment with adjuvant RT were independent predictors of survival. Five-year actuarial pelvic control was improved significantly with the delivery of adjuvant RT (74% vs. 49%; p = 0.011). Depth of myometrial invasion and treatment with adjuvant RT were independent predictors of pelvic control in multivariate analysis. Conclusions: Multiple prognostic factors predicting for the outcome of pathologic Stage III endometrial cancer patients were identified in this analysis. In particular, delivery of adjuvant RT seems to be a significant independent predictor for improved survival and pelvic control, suggesting that pelvic RT should be routinely considered in the management of these patients
Gong, Baolan; Yue, Yan; Wang, Renxiao; Zhang, Yi; Jin, Quanfang; Zhou, Xi
2017-06-01
The epithelial-mesenchymal transition is the key process driving cancer metastasis. MicroRNA-194 inhibits epithelial-mesenchymal transition in several cancers and its downregulation indicates a poor prognosis in human endometrial carcinoma. Self-renewal factor Sox3 induces epithelial-mesenchymal transition at gastrulation and is also involved epithelial-mesenchymal transition in several cancers. We intended to determine the roles of Sox3 in inducing epithelial-mesenchymal transition in endometrial cancer stem cells and the possible role of microRNA-194 in controlling Sox3 expression. Firstly, we found that Sox3 and microRNA-194 expressions were associated with the status of endometrial cancer stem cells in a panel of endometrial carcinoma tissue, the CD133+ cell was higher in tumorsphere than in differentiated cells, and overexpression of microRNA-194 would decrease CD133+ cell expression. Silencing of Sox3 in endometrial cancer stem cell upregulated the epithelial marker E-cadherin, downregulated the mesenchymal marker vimentin, and significantly reduced cell invasion in vitro; overexpression of Sox3 reversed these phenotypes. Furthermore, we discovered that the expression of Sox3 was suppressed by microRNA-194 through direct binding to the Sox3 3'-untranslated region. Ectopic expression of microRNA-194 in endometrial cancer stem cells induced a mesenchymal-epithelial transition by restoring E-cadherin expression, decreasing vimentin expression, and inhibiting cell invasion in vitro. Moreover, overexpression of microRNA-194 inhibited endometrial cancer stem cell invasion or metastasis in vivo by injection of adenovirus microRNA-194. These findings demonstrate the novel mechanism by which Sox3 contributes to endometrial cancer stem cell invasion and suggest that repression of Sox3 by microRNA-194 may have therapeutic potential to suppress endometrial carcinoma metastasis. The cancer stem cell marker, CD133, might be the surface marker of endometrial cancer stem
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Zhang, Hualin; Donnelly, Eric D.; Strauss, Jonathan B.; Qi, Yujin
2016-01-01
Purpose: To evaluate high-dose-rate (HDR) vaginal cuff brachytherapy (VCBT) in the treatment of endometrial cancer in a cylindrical target volume with either a varied or a constant cancer cell distributions using the linear quadratic (LQ) model. Methods: A Monte Carlo (MC) technique was used to calculate the 3D dose distribution of HDR VCBT over a variety of cylinder diameters and treatment lengths. A treatment planning system (TPS) was used to make plans for the various cylinder diameters, treatment lengths, and prescriptions using the clinical protocol. The dwell times obtained from the TPS were fed into MC. The LQ model was used to evaluate the therapeutic outcome of two brachytherapy regimens prescribed either at 0.5 cm depth (5.5 Gy × 4 fractions) or at the vaginal mucosal surface (8.8 Gy × 4 fractions) for the treatment of endometrial cancer. An experimentally determined endometrial cancer cell distribution, which showed a varied and resembled a half-Gaussian distribution, was used in radiobiology modeling. The equivalent uniform dose (EUD) to cancer cells was calculated for each treatment scenario. The therapeutic ratio (TR) was defined by comparing VCBT with a uniform dose radiotherapy plan in term of normal cell survival at the same level of cancer cell killing. Calculations of clinical impact were run twice assuming two different types of cancer cell density distributions in the cylindrical target volume: (1) a half-Gaussian or (2) a uniform distribution. Results: EUDs were weakly dependent on cylinder size, treatment length, and the prescription depth, but strongly dependent on the cancer cell distribution. TRs were strongly dependent on the cylinder size, treatment length, types of the cancer cell distributions, and the sensitivity of normal tissue. With a half-Gaussian distribution of cancer cells which populated at the vaginal mucosa the most, the EUDs were between 6.9 Gy × 4 and 7.8 Gy × 4, the TRs were in the range from (5.0)"4 to (13.4)"4 for
Filigheddu, Nicoletta; Sampietro, Sara; Chianale, Federica; Porporato, Paolo E; Gaggianesi, Miriam; Gregnanin, Ilaria; Rainero, Elena; Ferrara, Michele; Perego, Beatrice; Riboni, Francesca; Baldanzi, Gianluca; Graziani, Andrea; Surico, Nicola
2011-12-01
Increased levels of endogenous and/or exogenous estrogens are one of the well known risk factors of endometrial cancer. Diacylglycerol kinases (DGKs) are a family of enzymes which phosphorylate diacylglycerol (DAG) to produce phosphatidic acid (PA), thus turning off and on DAG-mediated and PA-mediated signaling pathways, respectively. DGK α activity is stimulated by growth factors and oncogenes and is required for chemotactic, proliferative, and angiogenic signaling in vitro. Herein, using either specific siRNAs or the pharmacological inhibitor R59949, we demonstrate that DGK α activity is required for 17-β-estradiol (E2)-induced proliferation, motility, and anchorage-independent growth of Hec-1A endometrial cancer cell line. Impairment of DGK α activity also influences basal cell proliferation and growth in soft agar of Hec-1A, while it has no effects on basal cell motility. Moreover, we show that DGK α activity induced by E2, as well as its observed effects, are mediated by the G protein-coupled estrogen receptor GPR30 (GPER). These findings suggest that DGK α may be a potential target in endometrial cancer therapy. Copyright © 2011 Elsevier Inc. All rights reserved.
Directory of Open Access Journals (Sweden)
Dundas George
2007-05-01
Full Text Available Abstract Background Despite evidence of the benefits of exercise in cancer survivors, exercise participation rates tend to decline after treatments. Few studies have examined the determinants of exercise in less common cancer sites. In this study, we examined medical, demographic, and social cognitive correlates of exercise in endometrial cancer survivors using the Theory of Planned Behavior (TPB. Methods A mailed survey was completed by 354 endometrial cancer survivors (1 to 10 years postdiagnosis residing in Alberta, Canada. The study was cross-sectional. Exercise behavior was assessed using the Godin Leisure Time Exercise Questionnaire and the TPB constructs were assessed with standard self-report scales. Multiple regression analyses were used to determine the independent associations of the TPB constructs with intention and behavior. Results Chi-square analyses indicated that marital status (p = .003, income level (p = .013, and body mass index (BMI (p = .020 were associated with exercise. The TPB explained 34.1% of the variance in exercise behavior with intention (β = .38, p β = .18, p = .029 being independent correlates. For intention, 38.3% of the variance was explained by the TPB with self-efficacy (β = .34, p β = .30, p Conclusion The TPB may be a useful framework for understanding exercise in endometrial cancer survivors. Exercise behavior change interventions based on the TPB should be tested in this growing population.
Molecular Biology and Prevention of Endometrial Cancer
National Research Council Canada - National Science Library
Maxwell, George L
2006-01-01
To increase our understanding of the molecular aberrations associated with endometrial carcinogenesis and the biologic mechanisms underlying the protective effect of oral contraceptive (OC) therapy. 1...
Molecular Biology and Prevention of Endometrial Cancer
National Research Council Canada - National Science Library
Maxwell, George
2003-01-01
To increase our understanding of the molecular aberrations associated with endometrial carcinogenesis and the biologic mechanisms underlying the protective effect of oral contraceptive therapy. Methods: 1...
Molecular Biology and Prevention of Endometrial Cancer
National Research Council Canada - National Science Library
Maxwell, George L
2004-01-01
To increase our understanding of the molecular aberrations associated with endometrial carcinogenesis and the biologic mechanisms underlying the protective effect of oral contraceptive therapy. Methods: 1...
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Monroe, Alan T.; Peddada, Anuj V. [Dept. of Radiation Oncology, Penrose Cancer Center, Colorado Springs (United States); Pikaart, Dirk [Dept. of Gynecologic Oncology, Penrose Cancer Center, Colorado Springs (United States)
2013-06-15
Objective. To report two year clinical outcomes of image guided radiation therapy (IGRT) to the vaginal cuff and pelvic lymph nodes in a series of high-risk endometrial cancer patients. Methods . Twenty-six consecutive high-risk endometrial cancer patients requiring adjuvant radiation to the vaginal cuff and regional lymph nodes were treated with vaginal cuff fiducial-based IGRT. Seventeen (65%) received sequential chemotherapy, most commonly with a sandwich technique. Brachytherapy followed external radiation in 11 patients to a median dose of 18 Gy in 3 fractions. The median external beam dose delivered was 47.5 Gy in 25 fractions. Results. All 656 fractions were successfully imaged and treated. The median overall translational shift required for correction was 9.1 mm (standard deviation, 5.2 mm) relative to clinical set-up with skin tattoos. Shifts of 1 cm, 1.5 cm, and 2 cm or greater were performed in 43%, 14%, and 4% of patients, respectively. Acute grade 2 gastrointestinal (GI) toxicity occurred in eight patients (30%) and grade 3 toxicity occurred in one. At two years, there have been no local or regional failures and actuarial overall survival is 95%. Conclusion. Daily image guidance for high-risk endometrial cancer results in a low incidence of acute GI/genitourinary (GU) toxicity with uncompromised tumor control at two years. Vaginal cuff translations can be substantial and may possibly result in underdosing if not properly considered.
International Nuclear Information System (INIS)
Monroe, Alan T.; Peddada, Anuj V.; Pikaart, Dirk
2013-01-01
Objective. To report two year clinical outcomes of image guided radiation therapy (IGRT) to the vaginal cuff and pelvic lymph nodes in a series of high-risk endometrial cancer patients. Methods . Twenty-six consecutive high-risk endometrial cancer patients requiring adjuvant radiation to the vaginal cuff and regional lymph nodes were treated with vaginal cuff fiducial-based IGRT. Seventeen (65%) received sequential chemotherapy, most commonly with a sandwich technique. Brachytherapy followed external radiation in 11 patients to a median dose of 18 Gy in 3 fractions. The median external beam dose delivered was 47.5 Gy in 25 fractions. Results. All 656 fractions were successfully imaged and treated. The median overall translational shift required for correction was 9.1 mm (standard deviation, 5.2 mm) relative to clinical set-up with skin tattoos. Shifts of 1 cm, 1.5 cm, and 2 cm or greater were performed in 43%, 14%, and 4% of patients, respectively. Acute grade 2 gastrointestinal (GI) toxicity occurred in eight patients (30%) and grade 3 toxicity occurred in one. At two years, there have been no local or regional failures and actuarial overall survival is 95%. Conclusion. Daily image guidance for high-risk endometrial cancer results in a low incidence of acute GI/genitourinary (GU) toxicity with uncompromised tumor control at two years. Vaginal cuff translations can be substantial and may possibly result in underdosing if not properly considered
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Yang, R; Wang, J [Peking University Third Hospital, Beijing, Beijing (China)
2014-06-01
Purpose: To investigate the feasibility, efficiency, and delivery accuracy of volumetric modulated arc therapy with constant dose rate (VMAT-CDR) for whole-pelvic radiotherapy (WPRT) of endometrial cancer. Methods: The nine-Field intensity-modulated radiotherapy (IMRT), VMAT with variable dose-rate (VMAT-VDR), and VMAT-CDR plans were created for 9 patients with endometrial cancer undergoing WPRT. The dose distribution of planning target volume (PTV), organs at risk (OARs), and normal tissue (NT) were compared. The monitor units (MUs) and treatment delivery time were also evaluated. For each VMAT-CDR plan, a dry Run was performed to assess the dosimetric accuracy with MatriXX from IBA. Results: Compared with IMRT, the VMAT-CDR plans delivered a slightly greater V20 of the bowel, bladder, pelvis bone, and NT, but significantly decreased the dose to the high-dose region of the rectum and pelvis bone. The MUs Decreased from 1105 with IMRT to 628 with VMAT-CDR. The delivery time also decreased from 9.5 to 3.2 minutes. The average gamma pass rate was 95.6% at the 3%/3 mm criteria with MatriXX pretreatment verification for 9 patients. Conclusion: VMAT-CDR can achieve comparable plan quality with significant shorter delivery time and smaller number of MUs compared with IMRT for patients with endometrial cancer undergoing WPRT. It can be accurately delivered and be an alternative to IMRT on the linear accelerator without VDR capability. This work is supported by the grant project, National Natural; Science Foundation of China (No. 81071237)
Seror, Julien; Bats, Anne-Sophie; Huchon, Cyrille; Bensaïd, Chérazade; Douay-Hauser, Nathalie; Lécuru, Fabrice
2014-01-01
To compare the rates of intraoperative and postoperative complications of robotic surgery and laparoscopy in the surgical treatment of endometrial cancer. Unicentric retrospective study (Canadian Task Force classification II-2). Tertiary teaching hospital. The study was performed from January 2002 to December 2011 and included patients with endometrial cancer who underwent laparoscopic or robotically assisted laparoscopic surgical treatment. Data collected included preoperative data, tumor characteristics, intraoperative data (route of surgery, surgical procedures, and complications), and postoperative data (early and late complications according to the Clavien-Dindo classification, and length of hospital stay). Morbidity was compared between the 2 groups. The study included 146 patients, of whom 106 underwent laparoscopy and 40 underwent robotically assisted surgery. The 2 groups were comparable in terms of demographic and preoperative data. Intraoperative complications occurred in 9.4% of patients who underwent laparoscopy and in none who underwent robotically assisted surgery (p = .06). There was no difference between the 2 groups in terms of postoperative events. Robotically assisted surgery is not associated with a significant difference in intraoperative and postoperative complications, even when there were no intraoperative complications of robotically assisted surgery. Copyright © 2014 AAGL. Published by Elsevier Inc. All rights reserved.
Treatment of Endometrial Cancer in Association with Pelvic Organ Prolapse
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Asama Vanichtantikul
2017-01-01
Full Text Available Background. Uterine malignancy coexistent with pelvic organ prolapse (POP is uncommon and standardized treatment is not established. The objective of this case study was to highlight the management of endometrial cancer in association with pelvic organ prolapse. Case Report. An 87-year-old woman presented with POP Stage IV combined with endometrioid adenocarcinoma of the uterus: clinical Stage IV B. She had multiple medical conditions including stroke, deep vein thrombosis, and pulmonary embolism. She was treated with radiotherapy and pessary was placed. Conclusion. Genital prolapse with abnormal uterine bleeding requires proper evaluation and management. Concurrent adenocarcinoma and POP can be a difficult clinical situation to treat, and optimum management is controversial.
Intraoperative visualization, frozen section, and permanent pathology in endometrial cancer
Directory of Open Access Journals (Sweden)
Soheila Aminimoghaddam
2014-12-01
Conclusion: Although the sample size of the studied population was small but our study results support the previous data and suggest that in early stages and low grade tumors, gross examination and frozen section diagnosis are conveniently predictive of lymph node metastasis. These data might be useful for prediction of tumor invasion using frozen section and gross examination in low grade tumors and early stages and for doing complete surgical staging and lymph node sampling. However the im-portance of surgical staging always must be considered in patients who need systemat-ic lymphadenectomy. In overall these data might help to come up with new guidelines for surgical risk assessment in endometrial cancer.
DEFF Research Database (Denmark)
Nastic, Denis; Shanwell, Emma; Wallin, Keng-Ling
2017-01-01
Grading and histologic typing of endometrial cancer in biopsy material has a direct impact on the decision to perform lymphadenectomy and/or omentectomy in many cancer centers. Endometrial biopsies are among the most common general surgical pathology specimens. Multiple studies have shown...... that biopsy diagnosis suffers from a lack of reproducibility. Although many biomarkers have been proposed, none have been demonstrated to improve the diagnosis in the biopsy setting. In this study, 70 biopsies with endometrial carcinoma were supplemented with a biomarker panel consisting of ER, PR, P53...
Independent prognostic value of peritoneal immunocytodiagnosis in endometrial carcinoma.
Benevolo, M; Mariani, L; Vocaturo, G; Vasselli, S; Natali, P G; Mottolese, M
2000-02-01
Among the clinical parameters that play a pivotal role in predicting the outcome of patients with endometrial carcinoma, intraperitoneal microscopic dissemination represents an important cause of recurrences. To date, peritoneal cytology has been incorporated into the current surgical staging system (International Federation of Gynecology and Obstetrics 88), although its predictive value remains a controversial issue. In this study the authors investigated the possibility of applying immunocytochemistry (ICC) to the diagnosis of peritoneal washing (PW) aimed at improving conventional cytology and verifying the prognostic value of peritoneal malignant cells. The authors analyzed 182 PWs sampled from endometrial cancer patients. The ICC analysis was performed using two monoclonal antibodies (MAbs)--AR-3 and B72.3--that in combination recognize more than 95% of endometrial carcinomas. The presence of peritoneal-free cancer cells was identified morphologically in 27 of 182 lavages (14.8%) and ICC in 50 of 182 (27.5%), with a significant improvement (p <0.0001). Five-year survival analysis, comparing results of ICC and cytodiagnosis, demonstrated a significant decrease of disease-free survival in patients with peritoneal microscopic disease. Furthermore, multivariate analysis showed that ICC diagnosis of PWs is an independent prognostic factor. Data indicate that the use of selected MAbs allows one to identify cytologically false-negative cases, providing results that are highly predictive of a worse clinical outcome.
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Nagar, Himanshu; Boothe, Dustin; Parikh, Amar; Yondorf, Menachem; Parashar, Bhupesh [Department of Radiation Oncology, Weill Cornell Medical College of Cornell University, New York, New York (United States); Gupta, Divya; Holcomb, Kevin; Caputo, Thomas [Division of Gynecological Oncology, Department of Obstetrics and Gynecology, Weill Cornell Medical College of Cornell University, New York, New York (United States); Chao, K. S. Clifford; Nori, Dattatreyudu [Department of Radiation Oncology, Weill Cornell Medical College of Cornell University, New York, New York (United States); Wernicke, A. Gabriella, E-mail: gaw9006@med.cornell.edu [Department of Radiation Oncology, Weill Cornell Medical College of Cornell University, New York, New York (United States)
2013-11-15
Purpose: To evaluate the tolerability and toxicity of administering vaginal brachytherapy (VB) concurrently during chemotherapy compared with the sequential approach for patients with endometrial cancer. Methods and Materials: A retrospective analysis of 372 surgically staged patients with endometrial cancer American Joint Committee on Cancer 2009 stages I to IV treated with adjuvant postoperative radiation therapy (RT) at our institution from 2001 to 2012 was conducted. All patients received VB + external beam RT (EBRT) + 6 cycles of adjuvant carboplatin- and paclitaxel-based chemotherapy. The VB mean dose was 15.08 Gy (range, 15-20 Gy), with 3 to 4 weekly applications, and the EBRT mean dose was 45 Gy delivered with 3-dimensional or intensity modulated RT techniques. Hematologic, gastrointestinal (GI), and genitourinary (GU) toxicities were assessed by Common Toxicity Criteria (CTC) and compared between sequential and concurrent chemotherapy and VB schedules. Results: Among patients who received RT and adjuvant chemotherapy, 180 of 372 patients (48%) received RT sandwiched between cycles 3 and 4 of chemotherapy. A separate group of 192 patients (52%) were treated with VB during the first 3 cycles of chemotherapy, with a weekly application on nonchemotherapy days, and received the EBRT portion in a sandwiched fashion. Patients treated with VB during chemotherapy had a decreased overall treatment time by 4 weeks (P<.001; 95% confidence interval: 3.99-4.02) and sustained no difference in CTC-graded acute hematologic, GI, or GU toxicities in comparison with the patients treated with VB and chemotherapy in a sequential manner (P>.05). CTC grade 3 or 4 hematologic, GI, and GU toxicities were zero. Conclusions: VB during chemotherapy is well tolerated, decreases overall treatment time, and does not render more toxicity than the sequential regimen.
International Nuclear Information System (INIS)
Wu, Hsien-Ming; Wang, Hsin-Shih; Huang, Hong-Yuan; Lai, Chyong-Huey; Lee, Chyi-Long; Soong, Yung-Kuei; Leung, Peter CK
2013-01-01
More than 25% of patients diagnosed with endometrial carcinoma have an invasive primary cancer accompanied by metastases. Gonadotropin-releasing hormone (GnRH) plays an important role in reproduction. In mammals, expression of GnRH-II is higher than GnRH-I in reproductive tissues. Here, we examined the effect of a GnRH-II agonist on the motility of endometrial cancer cells and its mechanism of action in endometrial cancer therapy. Immunoblotting and immunohistochemistry (IHC) were used to determine the expression of the GnRH-I receptor protein in human endometrial cancer. The activity of MMP-2 in the conditioned medium was determined by gelatin zymography. Cell motility was assessed by invasion and migration assay. GnRH-I receptor si-RNA was applied to knockdown GnRH-I receptor. The GnRH-I receptor was expressed in the endometrial cancer cells. The GnRH-II agonist promoted cell motility in a dose-dependent manner. The GnRH-II agonist induced the phosphorylation of ERK1/2 and JNK, and the phosphorylation was abolished by ERK1/2 inhibitor (U0126) and the JNK inhibitor (SP600125). Cell motility promoted by GnRH-II agonist was suppressed in cells that were pretreated with U0126 and SP600125. Moreover, U0126 and SP600125 abolished the GnRH-II agonist-induced activation of MMP-2. The inhibition of MMP-2 with MMP-2 inhibitor (OA-Hy) suppressed the increase in cell motility in response to the GnRH-II agonist. Enhanced cell motility mediated by GnRH-II agonist was also suppressed by the knockdown of the endogenous GnRH-I receptor using siRNA. Our study indicates that GnRH-II agonist promoted cell motility of endometrial cancer cells through the GnRH-I receptor via the phosphorylation of ERK1/2 and JNK, and the subsequent, MAPK-dependent activation of MMP-2. Our findings represent a new concept regarding the mechanism of GnRH-II-induced cell motility in endometrial cancer cells and suggest the possibility of exploring GnRH-II as a potential therapeutic target for the
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Woo, Sungmin [Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Kim, Sang Youn [Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Cho, Jeong Yeon; Kim, Seung Hyup [Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Seoul National University Medical Research Center, Institute of Radiation Medicine and Kidney Research Institute, Seoul (Korea, Republic of)
2017-05-15
To investigate the added value of secondary reports issued by radiologists subspecializing in gynaecologic imaging for determining deep myometrial invasion of endometrial cancer on MRI. Initial (from referring institutions) and secondary (by subspecialized radiologists) interpretations of MRI of 55 patients with endometrial cancer were retrospectively reviewed. A radiologist blinded to clinicopathological information assessed both reports for the presence of deep myometrial invasion. Reference standard was based on hysterectomy specimens. Kappa coefficients (k) were used to measure their concordance. McNemar testing and receiver operating characteristic (ROC) analysis was used to compare sensitivities, specificities and areas under the curves (AUCs). Deep myometrial invasion was present in 25 (45.5 %) patients. Among 27.3 % (15/55; k = 0.458) patients with discrepant results, secondary interpretations were correct in 10 (66.7 %) cases. Sensitivity was higher in secondary than in initial reports (76.0 % vs. 48.0 %, p = 0.039) while no significant difference was seen in specificity (70.0 % vs. 76.7 %, p = 0.668). At ROC analysis, there was a tendency for higher AUCs in secondary reports (0.785 vs 0.669, p = 0.096). Secondary readings of MRI by subspecialized gynaecologic oncologic radiologists may provide incremental value in determining deep myometrial invasion of endometrial cancer. (orig.)
Huang, Marilyn; Sun, Charlotte; Boyd-Rogers, Stephanie; Burzawa, Jennifer; Milbourne, Andrea; Keeler, Elizabeth; Yzquierdo, Rebecca; Lynch, Patrick; Peterson, Susan K.; Lu, Karen
2011-01-01
Background: Endometrial and colorectal cancers are the most common cancers in Lynch syndrome. Consensus guidelines recommend annual endometrial biopsy (EMB) and regular colonoscopies. We assessed the feasibility of concurrently performing EMB and colonoscopy and evaluated women's perception of pain, satisfaction, and acceptability. Methods: From July 2002 to December 2009, women who had a gene mutation for Lynch syndrome, met the Amsterdam II criteria, or had a high-risk situation that required screening were prospectively enrolled. After conscious sedation, the procedures were sequentially performed. Patients completed pre- and postprocedure questionnaires assessing pain, level of satisfaction, and acceptability. The Wilcoxon rank test and Mann-Whitney test were used to compare pain scores. Results: Forty-two women completed the study. Median age was 37 years (range, 25 to 73). Nineteen had previously had an EMB in the office setting. Women reported significantly lower median levels of pain in the combined procedure compared with previous office setting biopsies (P Lynch syndrome screening recommendations. PMID:21532810
DEFF Research Database (Denmark)
Small, W.Jr.; Bois, A. Du; Bhatnagar, S.
2009-01-01
PURPOSE: To describe radiotherapeutic practice of the treatment of endometrial cancer in members of the Gynecologic Cancer Intergroup (GCIG). METHODS: A survey was developed and distributed to the members of the GCIG. The GCIG is a global association of cooperative groups involved in the research.......57 [10.13] Gy in a mean of 4.3 insertions), and 5 groups used low-dose-rate brachytherapy (41.45 [17.5] Gy). Nineteen of the 28 respondents measured the doses to the bladder and the rectum when performing VBT. For brachytherapy, there was no uniformity in the fraction of the vagina treated or the doses...... and schedules used. CONCLUSIONS: Radiotherapy practices among member groups of the GCIG are similar in doses and dose per fraction with external beam. There is a moderate discrepancy in the brachytherapy practice after hysterectomy. There are no serious impediments to intergroup participation in radiation...
International Nuclear Information System (INIS)
Chung, Hyun Hoon; Kim, Jae Weon; Park, Noh-Hyun; Song, Yong-Sang; Kang, Soon-Beom; Kang, Won Jun; Chung, June-Key
2008-01-01
The purpose of this study was to evaluate the accuracy of integrated positron emission tomography (PET) and computed tomography (CT) for the identification of suspected recurrent endometrial cancer after treatment. Thirty-one women (median age, 53 years) with endometrial cancer treated by primary staging laparotomy who had [ 18 F]fluorodeoxyglucose (FDG) PET/CT performed for suspected recurrence were retrospectively reviewed. The findings of the PET/CT scans were compared, with the histological examination after a surgical biopsy in 20 cases and with clinical follow-up in 11 cases to determine the diagnostic accuracy of PET/CT. Twelve (38.7%) of the 31 patients had a documented recurrence by surgical biopsy or clinical follow-up, and 19 (61.3%) had no evidence of recurrence. Of the 12 patients with recurrent disease, nine (75.0%) women were confirmed to have a recurrence by surgical biopsy. A close correlation was found between the PET/CT and histological or clinical analyses (κ = 0.933, p < 0.001). The overall sensitivity, specificity, accuracy, positive predictive value, negative predictive value, and accuracy of PET/CT were 100, 94.7, 92.3, 100, and 96.8%, respectively. The PET/CT results modified the diagnostic or treatment plan in seven (22.6%) patients, resulting in five (16.1%) patients undergoing previously unplanned therapeutic procedures and eliminating previously planned diagnostic procedures in two (6.5%) patients. Patients with negative PET/CT scans showed significantly better progression-free survival than those with positive scans (p = 0.015). Integrated PET/CT appears to be highly sensitive, specific, and accurate as a post-therapy surveillance modality for endometrial cancer in well-selected patients. The PET/CT might be used to improve patient surveillance and prognosis. (orig.)
Androgen responsiveness of the new human endometrial cancer cell line MFE-296.
Hackenberg, R; Beck, S; Filmer, A; Hushmand Nia, A; Kunzmann, R; Koch, M; Slater, E P; Schulz, K D
1994-04-01
MFE-296 endometrial cancer cells express androgen receptors in vitro. These cells, which are tumorigenic in nude mice, are derived from a moderately differentiated human endometrial adenocarcinoma. They express vimentin and the cytokeratins 7, 8, 18, and 19. Karyotyping revealed near-tetraploidy for most of the cells. No marker chromosomes were observed. DNA analyses confirmed the genetic identity of the cell line and the patient from whom the cell line was derived. Proliferation of MFE-296 cells was inhibited by the progestin R5020 and the androgen dihydrotestosterone (DHT). The inhibition of proliferation by DHT was antagonized by the antiandrogen Casodex, demonstrating the involvement of the androgen receptor. Androgen binding was determined at 22,000 binding sites per cell using a whole-cell assay (KD = 0.05 nM) and 30 fmol/mg protein with the dextran charcoal method; 7 fmol/mg protein of progesterone receptors were found, whereas estrogen receptors were below 5 fmol/mg protein. The androgen receptor was functionally intact, as demonstrated by transfection experiments with a reporter-gene construct, containing an androgen-responsive element. In MFE-296 cells the content of the androgen receptor was up-regulated by its own ligand.
Directory of Open Access Journals (Sweden)
Suna Kabil Kucur
2013-01-01
Full Text Available ive: To investigate the diagnostic value of blood flow measurements in spiral artery by transvaginal color Doppler sonography (CDS in predicting endometrial pathologies.Methods: Ninety-seven patients presenting with abnormal uterine bleeding and requiring endometrial assessment were included in this prospective observational study. Endometrial thickness, structure and echogenicity were recorded. Pulsatility index (PI and resistive index (RI of the spiral artery were measured by transvaginal CDS. Endometrial sampling was performed for all subjects. Sonographic and hystopathologic findings were compared.Results: The histopathological diagnoses were as follows; 39 cases (40.2% endometrial polyp, 9 cases (9.3% endometrial hyperplasia, 10 cases (10.3 submucous myoma, 7 cases (7.2% endometrium cancer, and 32 cases (33% nonspecific findings. The spiral artery PI in endometrium cancer group was highly significantly lower than other groups (p<0.01. The spiral artery RI was also significantly lower in the patients with malignant histology (p<0.05. Conclusion: Endometrial pathologies are associated significantly with endometrial spiral artery Doppler changes.Key words: Spiral artery, Doppler ultrasonography, endometrium
Directory of Open Access Journals (Sweden)
John eRisinger
2013-06-01
Full Text Available Endometrial cancer is the most common gynecologic malignancy in the United States but it remains poorly understood at the molecular level. This investigation was conducted to specifically assess whether gene expression changes underlie the clinical and pathologic factors traditionally used for determining treatment regimens in women with stage I endometrial cancer. These include the effect of tumor grade, depth of myometrial invasion and histotype. We utilized oligonucleotide microarrays to assess the transcript expression profile in epithelial glandular cells laser microdissected from 79 endometrioid and 12 serous stage I endometrial cancers with a heterogeneous distribution of grade and depth of myometrial invasion, along with 12 normal post-menopausal endometrial samples. Unsupervised multidimensional scaling analyses revealed that serous and endometrioid stage I cancers have similar transcript expression patterns when compared to normal controls where 900 transcripts were identified to be differentially expressed by at least 4-fold (univariate t-test, p <0.001 between the cancers and normal endometrium. This analysis also identified transcript expression differences between serous and endometrioid cancers and tumor grade, but no apparent differences were identified as a function of depth of myometrial invasion. Four genes were validated by quantitative PCR on an independent set of cancer and normal endometrium samples. These findings indicate that unique gene expression profiles are associated with histologic type and grade, but not myometrial invasion among early stage endometrial cancers. These data provide a comprehensive perspective on the molecular alterations associated with stage I endometrial cancer, particularly those subtypes that have the worst prognosis.
Zapardiel, Ignacio; Blancafort, Claudia; Cibula, David; Jaunarena, Ibon; Gorostidi, Mikel; Gil-Moreno, Antonio; De Santiago, Javier
2017-07-01
The aim of the study was to analyze the current management of endometrial cancer across Spain and to evaluate the use and applicability of the national and international guidelines. An electronic 30-question survey was distributed among all Spanish Society of Obstetrics and Gynecology-registered specialists dedicated to gynecologic oncology in Spain by e-mail. Data were collected anonymously and analyzed using SPSS program. One hundred forty-five (17.8%) surveys were collected. Significant differences were observed between tertiary hospitals and secondary or private hospitals in terms of appropriate (according to European Society of Gynaecologic Oncology guidelines) nodal staging in low-risk cases (96 [95%] vs 27 [61.4%], respectively; P comparing centers with less than 20 cases per year to centers with more than 40 cases annually, with significant differences in the management of low-risk and intermediate-risk endometrial cancers. This cross-sectional study demonstrates a broad heterogeneity of care giving between the clinical national and international guidelines and the actual practice in Spain. Although most of the responders refer to base their endometrial cancer management on Spanish and European Society of Gynaecologic Oncology guidelines (64.1%), many discrepancies have been observed, mainly in the management of intermediate-risk cases and follow-up. It may be caused by the lack of consensus on certain points, lack of facilities in lower case load centers, and also due to disagreement or unawareness on the current knowledge.
Dillon, Jessica L; Gonzalez, Jorge L; DeMars, Leslie; Bloch, Katarzyna J; Tafe, Laura J
2017-12-01
Lynch syndrome (LS) is an inherited clinical syndrome characterized by a high risk of colorectal, endometrial (lifetime risk of up to 60%), ovarian, and urinary tract cancers. The diagnosis is confirmed by identification of germline mutations in the DNA mismatch repair genes MLH1, PMS2, MSH2, MSH6, or EPCAM. In 2015, our institution implemented universal screening of endometrial cancer (EC) hysterectomy specimens by mismatch repair immunohistochemistry (IHC) with reflex MLH1 promoter hypermethylation analysis for tumors with loss of MLH1/PMS2 expression. Patients with tumors negative for MLH1 methylation and those with a loss of the heterodimer pair MSH2 and MSH6, or isolated loss of either PMS2 or MSH6 were referred to the Familial Cancer Program for genetic counseling and consideration of germline testing. Between May 2015 to Dec 2016, 233 EC patients were screened by IHC for LS with a median age of 63 years. Sixty tumors (27%) had abnormal IHC staining results. Fifty-one (22%) harbored heterodimeric loss of MLH1 and PMS2, 49 of which showed MLH1 promoter methylation (1 failure, 1 negative). One showed loss of MLH1/PMS2 and MSH6, 2 showed loss of MSH2/MSH6, and 6 had isolated loss of MSH6 only. Ten patients underwent genetic counseling, and germline testing was performed in 8; LS was confirmed in 5 patients (2.1%). In addition, 3 patients with negative germline testing and presumed Lynch-like syndrome were identified and offered additional somatic testing. Universal screening for LS in EC patients has yielded positive results for identification of patients at risk for this inherited syndrome. Copyright © 2017 Elsevier Inc. All rights reserved.
Uccella, Stefano; Bonzini, Matteo; Palomba, Stefano; Fanfani, Francesco; Ceccaroni, Marcello; Seracchioli, Renato; Vizza, Enrico; Ferrero, Annamaria; Roviglione, Giovanni; Casadio, Paolo; Corrado, Giacomo; Scambia, Giovanni; Ghezzi, Fabio
2016-01-01
To evaluate the impact of obesity on the outcomes of surgical treatment for endometrial cancer in general and also comparing laparoscopic and open abdominal approach. Retrospective case-control study (Canadian Task Force classification II-1). Obstetrics and Gynecology Department, University of Insubria, Varese, Catholic University of the Sacred Heart, Rome, International School of Surgical Anatomy, Sacred Heart Hospital, Negrar, and Sant'Orsola-Malpighi Hospital, Bologna, Italy. Data of consecutive patients who underwent surgery for endometrial cancer in 4 centers were reviewed. Univariate and multivariable analyses were performed. Adjustment for potential selection bias in surgical approach was made using propensity score (PS) matching. Laparoscopic or open surgical treatment for endometrial cancer. A total of 1266 patients were included, including 764 in the laparoscopy group and 502 in the open surgery group. A total of 391 patients (30.9%) were obese, including 238 (18.8%) with class I obesity, 89 (7%) with class II obesity, and 64 (5.1%) with class III obesity. The total number of complications, risk of wound complications, and venous thromboembolic events were higher in obese women compared with nonobese women. Blood transfusions, incidence/severity of postoperative complications, and postoperative hospital stay were significantly higher in the open surgery group compared with the laparoscopy group, irrespective of obesity. These differences remained significant in both multivariable analysis and PS-matched analysis. The percentage of patients who received lymphadenectomy declined significantly in patients with BMI ≥40 in both the laparoscopy and open surgery groups. Conversions from the initially intended minimally invasive approach to open surgery were 1.1% to 2.2% for women with BMI obese women in the laparoscopic group. Laparoscopy for endometrial cancer retains its advantages over open surgery, even in obese patients. However, operating on obese
Brachytherapy of endometrial cancers
International Nuclear Information System (INIS)
Peiffert, D.; Hoffstetter, S.; Charra-Brunaud, C.
2003-01-01
Endometrial adenocarcinomas rank third as tumoral sites en France. The tumors are confined to the uterus in 80% of the cases. Brachytherapy has a large place in the therapeutic strategy. The gold standard treatment remains extra-fascial hysterectomy with bilateral annexiectomy and bilateral internal iliac lymph node dissection. However, after surgery alone, the rate of locoregional relapses reaches 4-20%, which is reduced to 0-5% after postoperative brachytherapy of the vaginal cuff. This postoperative brachytherapy is delivered as outpatients treatment, by 3 or 4 fractions, at high dose rate. The utero-vaginal preoperative brachytherapy remains well adapted to the tumors which involve the uterine cervix. Patients presenting a localized tumor but not operable for general reasons (< 10%) can be treated with success by exclusive irradiation, which associates a pelvic irradiation followed by an utero-vaginal brachytherapy. A high local control of about 80-90% is obtained, a little lower than surgery, with a higher risk of late complications. Last but not least, local relapses in the vaginal cuff, or in the perimeatic area, can be treated by interstitial salvage brachytherapy, associated if possible with external beam irradiation. The local control is reached in half of the patients, but metastatic dissemination is frequent. We conclude that brachytherapy has a major role in the treatment of endometrial adenocarcinomas, in combination with surgery, or with external beam irradiation for not operable patients or in case of local relapses. It should use new technologies now available including computerized after-loaders and 3D dose calculation. (authors)
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Diavolitsis, V. [Department of Radiation Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL (United States); Rademaker, A. [Department of Preventive Medicine, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL (United States); Lurain, J.; Hoekstra, A. [Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL (United States); Strauss, J. [Department of Radiation Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL (United States); Small, W., E-mail: wsmall@nmff.org [Department of Radiation Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL (United States)
2012-10-01
Purpose: To assess the clinical outcomes of patients with Stage IA endometrial cancer with myometrial invasion treated with postoperative vaginal brachytherapy (VBT) with those who received no adjuvant therapy (NAT). Methods and Materials: All patients treated with hysterectomy for endometrial cancer at Northwestern Memorial Hospital between 1978 and 2005 were identified. Those patients with Stage IA disease with myometrial invasion who were treated with VBT alone or NAT were identified and included in the present analysis. Results: Of 252 patients with Stage IA endometrial cancer with superficial (<50%) myometrial invasion who met the inclusion criteria, 169 underwent VBT and 83 received NAT. The median follow-up in the VBT and NAT groups was 103 and 61 months, respectively. In the VBT group, 56.8% had Grade 1, 37.9% had Grade 2, and 5.3% had Grade 3 tumors. In the NAT group, 75.9%, 20.5%, and 3.6% had Grade 1, 2, and 3 tumors, respectively. Lymphatic or vascular space invasion was noted in 12.4% of the VBT patients and 5.6% of the NAT patients. The 5-year overall survival rate was 95.5%. The 5-year recurrence-free survival rate was 92.4% for all patients, 94.4% for the VBT group, and 87.4% for the NAT group (p = NS). Of the 169 VBT patients and 83 NAT patients, 8 (4.7%) and 6 (7.2%) developed recurrent disease. One vaginal recurrence occurred in the VBT group (0.6%) and three in the NAT group (3.8%). Recurrences developed 2-102 months after surgical treatment. Two of the four vaginal recurrences were salvaged. No Grade 3 or higher acute or late radiation toxicity was noted. Conclusions: The use of postoperative VBT in patients with Stage I endometrial cancer with <50% myometrial invasion yielded excellent vaginal disease control and disease-free survival, with minimal toxicity.
Hypoxia-Inducible Factor-1 as a Therapeutic Target in Endometrial Cancer Management
Directory of Open Access Journals (Sweden)
Laura M. S. Seeber
2010-01-01
Full Text Available In the Western world, endometrial cancer (EC is the most common malignant tumor of the female genital tract. Solid tumors like EC outgrow their vasculature resulting in hypoxia. Tumor hypoxia is important because it renders an aggressive phenotype and leads to radio- and chemo-therapy resistance. Hypoxia-inducible factor-1 (HIF-1 plays an essential role in the adaptive cellular response to hypoxia and is associated with poor clinical outcome in EC. Therefore, HIF-1 could be an attractive therapeutic target. Selective HIF-1 inhibitors have not been identified. A number of nonselective inhibitors which target signaling pathways upstream or downstream HIF-1 are known to decrease HIF-1 protein levels. In clinical trials for the treatment of advanced and/or recurrent EC are the topoisomerase I inhibitor Topotecan, mTOR-inhibitor Rapamycin, and angiogenesis inhibitor Bevacizumab. Preliminary data shows encouraging results for these agents. Further work is needed to identify selective HIF-1 inhibitors and to translate these into clinical trials.
International Nuclear Information System (INIS)
Izmajlowicz, B.; Komafel, J.
2010-01-01
Aim of the study. The purpose of this prospective study was to analyze and compare acute and late side-effects observed in patients with cervical and endometrial cancer treated with conventional 2-dimensional (2D) and conformal 3-dimensional (3D) pelvic radiotherapy. Patients and method. 50 patients treated with conventional pelvic radiotherapy and 50 patients treated with conformal pelvic radiotherapy at the Clinical Department of Gynecological Radiotherapy of the Lower Silesian Oncology Center between November 2004 and October 2005 were entered into a prospective study. We assessed Radiotherapy side-effects according to EORTCIRTOG, performance status according to the WHO, Body Mass Index and hematologic parameters during radiotherapy and one year after treatment. Results. Performance status acc. to the WHO was significantly better in the conformal arm. Anemia and nausea were more frequent in the conventional arm. In both the study groups acute gastrointestinal and genitourinary morbidity was more frequent than late morbidity and performance status was better after than before radiotherapy. Mean BMI was lower after radiotherapy than before treatment. Conclusions. Conformal pelvic radiotherapy in patients with cervical and endometrial cancer is less toxic than conventional pelvic radiotherapy which is also confirmed by the performance status. (authors)
DEFF Research Database (Denmark)
Herling, Suzanne Forsyth
2016-01-01
the last decade without randomised controlled trials (RCTs) to prove superiority over other surgical alternatives. The purpose of the thesis was to explore and describe patient and health economic outcomes of RALH for women with endometrial cancer using different research approaches. The first study...... weeks earlier. The women were positive towards the robotic approach and felt recovered shortly after. They expressed uncertainty with the normal course of bleeding and bowel movement post-operatively as well as with the new anatomy. The third study was an economic evaluation; an activity-based costing...... to monitor relevant surgical and patient-reported outcomes as indications for robotic surgery may alter, experiences may develop and further technical advances may change robotic surgery for women with endometrial cancer in the future....
Kang, Sokbom; Lee, Jong-Min; Lee, Jae-Kwan; Kim, Jae-Weon; Cho, Chi-Heum; Kim, Seok-Mo; Park, Sang-Yoon; Park, Chan-Yong; Kim, Ki-Tae
2014-03-01
The purpose of this study is to develop a Web-based nomogram for predicting the individualized risk of para-aortic nodal metastasis in incompletely staged patients with endometrial cancer. From 8 institutions, the medical records of 397 patients who underwent pelvic and para-aortic lymphadenectomy as a surgical staging procedure were retrospectively reviewed. A multivariate logistic regression model was created and internally validated by rigorous bootstrap resampling methods. Finally, the model was transformed into a user-friendly Web-based nomogram (http://http://www.kgog.org/nomogram/empa001.html). The rate of para-aortic nodal metastasis was 14.4% (57/397 patients). Using a stepwise variable selection, 4 variables including deep myometrial invasion, non-endometrioid subtype, lymphovascular space invasion, and log-transformed CA-125 levels were finally adopted. After 1000 repetitions of bootstrapping, all of these 4 variables retained a significant association with para-aortic nodal metastasis in the multivariate analysis-deep myometrial invasion (P = 0.001), non-endometrioid histologic subtype (P = 0.034), lymphovascular space invasion (P = 0.003), and log-transformed serum CA-125 levels (P = 0.004). The model showed good discrimination (C statistics = 0.87; 95% confidence interval, 0.82-0.92) and accurate calibration (Hosmer-Lemeshow P = 0.74). This nomogram showed good performance in predicting para-aortic metastasis in patients with endometrial cancer. The tool may be useful in determining the extent of lymphadenectomy after incomplete surgery.
Cosgrove, Casey M; Tritchler, David L; Cohn, David E; Mutch, David G; Rush, Craig M; Lankes, Heather A; Creasman, William T; Miller, David S; Ramirez, Nilsa C; Geller, Melissa A; Powell, Matthew A; Backes, Floor J; Landrum, Lisa M; Timmers, Cynthia; Suarez, Adrian A; Zaino, Richard J; Pearl, Michael L; DiSilvestro, Paul A; Lele, Shashikant B; Goodfellow, Paul J
2018-01-01
The purpose of this study was to assess the prognostic significance of a simplified, clinically accessible classification system for endometrioid endometrial cancers combining Lynch syndrome screening and molecular risk stratification. Tumors from NRG/GOG GOG210 were evaluated for mismatch repair defects (MSI, MMR IHC, and MLH1 methylation), POLE mutations, and loss of heterozygosity. TP53 was evaluated in a subset of cases. Tumors were assigned to four molecular classes. Relationships between molecular classes and clinicopathologic variables were assessed using contingency tests and Cox proportional methods. Molecular classification was successful for 982 tumors. Based on the NCI consensus MSI panel assessing MSI and loss of heterozygosity combined with POLE testing, 49% of tumors were classified copy number stable (CNS), 39% MMR deficient, 8% copy number altered (CNA) and 4% POLE mutant. Cancer-specific mortality occurred in 5% of patients with CNS tumors; 2.6% with POLE tumors; 7.6% with MMR deficient tumors and 19% with CNA tumors. The CNA group had worse progression-free (HR 2.31, 95%CI 1.53-3.49) and cancer-specific survival (HR 3.95; 95%CI 2.10-7.44). The POLE group had improved outcomes, but the differences were not statistically significant. CNA class remained significant for cancer-specific survival (HR 2.11; 95%CI 1.04-4.26) in multivariable analysis. The CNA molecular class was associated with TP53 mutation and expression status. A simple molecular classification for endometrioid endometrial cancers that can be easily combined with Lynch syndrome screening provides important prognostic information. These findings support prospective clinical validation and further studies on the predictive value of a simplified molecular classification system. Copyright © 2017 Elsevier Inc. All rights reserved.
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Kim, Ji Young [Department of Anatomy and Cell Biology, College of Medicine, Dong-A University, Busan 602-714 (Korea, Republic of); Medical Research Science Center, Dong-A University, Busan 602-714 (Korea, Republic of); Lee, Seung Gee [Department of Anatomy and Cell Biology, College of Medicine, Dong-A University, Busan 602-714 (Korea, Republic of); Mitochondria Hub Regulation Center, Dong-A University, Busan 602-714 (Korea, Republic of); Chung, Jin-Yong [Department of Anatomy and Cell Biology, College of Medicine, Dong-A University, Busan 602-714 (Korea, Republic of); Medical Research Science Center, Dong-A University, Busan 602-714 (Korea, Republic of); Kim, Yoon-Jae [Department of Anatomy and Cell Biology, College of Medicine, Dong-A University, Busan 602-714 (Korea, Republic of); Mitochondria Hub Regulation Center, Dong-A University, Busan 602-714 (Korea, Republic of); Park, Ji-Eun [Department of Anatomy and Cell Biology, College of Medicine, Dong-A University, Busan 602-714 (Korea, Republic of); Medical Research Science Center, Dong-A University, Busan 602-714 (Korea, Republic of); Oh, Seunghoon [Department of Physiology, College of Medicine, Dankook University, Cheonan 330-714 (Korea, Republic of); Lee, Se Yong [Department of Obstetrics and Gynecology, Busan Medical Center, Busan 611-072 (Korea, Republic of); Choi, Hong Jo [Department of General Surgery, College of Medicine, Dong-A University, Busan 602-714 (Korea, Republic of); Yoo, Young Hyun, E-mail: yhyoo@dau.ac.kr [Department of Anatomy and Cell Biology, College of Medicine, Dong-A University, Busan 602-714 (Korea, Republic of); Mitochondria Hub Regulation Center, Dong-A University, Busan 602-714 (Korea, Republic of); Medical Research Science Center, Dong-A University, Busan 602-714 (Korea, Republic of); and others
2012-04-15
7,12-Dimethylbenzanthracene (DMBA), a polycyclic aromatic hydrocarbon, exhibits mutagenic, carcinogenic, immunosuppressive, and apoptogenic properties in various cell types. To achieve these functions effectively, DMBA is modified to its active form by cytochrome P450 1 (CYP1). Exposure to DMBA causes cytotoxicity-mediated apoptosis in bone marrow B cells and ovarian cells. Although uterine endometrium constitutively expresses CYP1A1 and CYP1B1, their apoptotic role after exposure to DMBA remains to be elucidated. Therefore, we chose RL95-2 endometrial cancer cells as a model system for studying DMBA-induced cytotoxicity and cell death and hypothesized that exposure to DMBA causes apoptosis in this cell type following CYP1A1 and/or CYP1B1 activation. We showed that DMBA-induced apoptosis in RL95-2 cells is associated with activation of caspases. In addition, mitochondrial changes, including decrease in mitochondrial potential and release of mitochondrial cytochrome c into the cytosol, support the hypothesis that a mitochondrial pathway is involved in DMBA-induced apoptosis. Exposure to DMBA upregulated the expression of AhR, Arnt, CYP1A1, and CYP1B1 significantly; this may be necessary for the conversion of DMBA to DMBA-3,4-diol-1,2-epoxide (DMBA-DE). Although both CYP1A1 and CYP1B1 were significantly upregulated by DMBA, only CYP1B1 exhibited activity. Moreover, knockdown of CYP1B1 abolished DMBA-induced apoptosis in RL95-2 cells. Our data show that RL95-2 cells are susceptible to apoptosis by exposure to DMBA and that CYP1B1 plays a pivotal role in DMBA-induced apoptosis in this system. -- Highlights: ► Cytotoxicity-mediated apoptogenic action of DMBA in human endometrial cancer cells. ► Mitochondrial pathway in DMBA-induced apoptosis of RL95-2 endometrial cancer cells. ► Requirement of ligand-selective activation of CYP1B1 in DMBA-induced apoptosis.
International Nuclear Information System (INIS)
Narayan, K.; Bernshaw, D.; Quinn, M.; Allen, D.; Rejeki, V.; Herschtal, A.; Jobling, T.
2009-01-01
Full text: The purpose of the present study was to explore the prognostic significance of several histological features with respect to lymph node metastasis, failure-free survival (FeS), and overall survival (Os) in intermediate and high-risk endometrial cancer patients treated with curative intent. One hundred and eighty patients with endometrial cancer were treated with hysterectomy with or without lymphadenectomy and received external beam radiotherapy (EBRT). The mean follow-up period was 4.25 years (range 0.44-10.45 years). In multifactor analysis, fractional myometrial invasion (MI) (P = 0.047), histology (P < 0.001) and lymph-vascular space invasion (LVSI) (P = 0.025) were significant predictors for FFS when nodal status was not included. When lymph node status was known, histology (P - 0.007) and LVSI (P = 0.014) remained significant factors for FFS. For OS, histology (P < 0.001) and fractional MI (P = 0.004) were the significant factors. Lymph node status could be predicted by tumour grading (P = 0.016) and absolute MI (P 0.002). Histology type and the presence of LVSI were the most important prognostic factors in high-risk endometrial cancer patients treated by surgery and postoperative radiotherapy. Absolute MI and tumour grading were useful predictors of nodal spread.
McAlpine, Jessica; Leon-Castillo, Alicia; Bosse, Tjalling
2018-04-01
Endometrial cancer is a clinically heterogeneous disease and it is becoming increasingly clear that this heterogeneity may be a function of the diversity of the underlying molecular alterations. Recent large-scale genomic studies have revealed that endometrial cancer can be divided into at least four distinct molecular subtypes, with well-described underlying genomic aberrations. These subtypes can be reliably delineated and carry significant prognostic as well as predictive information; embracing and incorporating them into clinical practice is thus attractive. The road towards the integration of molecular features into current classification systems is not without obstacles. Collaborative studies engaging research teams from across the world are working to define pragmatic assays, improve risk stratification systems by combining molecular features and traditional clinicopathological parameters, and determine how molecular classification can be optimally utilized to direct patient care. Pathologists and clinicians caring for women with endometrial cancer need to engage with and understand the possibilities and limitations of this new approach, because integration of molecular classification of endometrial cancers is anticipated to become an essential part of gynaecological pathology practice. This review will describe the challenges in current systems of endometrial carcinoma classification, the evolution of new molecular technologies that define prognostically distinct molecular subtypes, and potential applications of molecular classification as a step towards precision medicine and refining care for individuals with the most common gynaecological cancer in the developed world. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Yokoyama, Takanori; Takehara, Kazuhiro; Sugimoto, Nao; Kaneko, Keika; Fujimoto, Etsuko; Okazawa-Sakai, Mika; Okame, Shinichi; Shiroyama, Yuko; Yokoyama, Takashi; Teramoto, Norihiro; Ohsumi, Shozo; Saito, Shinya; Imai, Kazuho; Sugano, Kokichi
2018-05-21
Lynch syndrome is an autosomal dominant inherited disease caused by germline mutations in mismatch repair genes. Analysis for microsatellite instability (MSI) and immunohistochemistry (IHC) of protein expressions of disease-associated genes is used to screen for Lynch syndrome in endometrial cancer patients. When losses of both MLH1 and PMS2 proteins are observed by IHC, MLH1 promoter methylation analysis is conducted to distinguish Lynch syndrome-associated endometrial cancer from sporadic cancer. Here we report a woman who developed endometrial cancer at the age of 49 years. She had a family history of colorectal cancer (first-degree relative aged 52 years) and stomach cancer (second-degree relative with the age of onset unknown). No other family history was present, and she failed to meet the Amsterdam II criteria for the diagnosis of Lynch syndrome. Losses of MLH1 and PMS2, but not MSH2 and MSH6, proteins were observed by IHC in endometrial cancer tissues. Because MLH1 promoter hypermethylation was detected in endometrial cancer tissue samples, the epigenetic silencing of MLH1 was suspected as the cause of the protein loss. However, because of the early onset of endometrial cancer and the positive family history, a diagnosis of Lynch syndrome was also suspected. Therefore, we provided her with genetic counseling. After obtaining her consent, MLH1 promoter methylation testing and genetic testing of peripheral blood were performed. MLH1 promoter methylation was not observed in peripheral blood. However, genetic testing revealed a large deletion of exon 5 in MLH1; thus, we diagnosed the presence of Lynch syndrome. Both MLH1 germline mutation and MLH1 promoter hypermethylation may be observed in endometrial cancer. Therefore, even if MLH1 promoter hypermethylation is detected, a diagnosis of Lynch syndrome cannot be excluded.
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Kitajima, Kazuhiro [Kobe University School of Medicine, Department of Radiology, Kobe (Japan); Kobe University Graduate School of Medicine, Department of Radiology, Kobe (Japan); Suenaga, Yuko; Ueno, Yoshiko; Maeda, Tetsuo; Sofue, Keitarou; Sugimura, Kazuro [Kobe University School of Medicine, Department of Radiology, Kobe (Japan); Ebina, Yasuhiko; Yamada, Hideto [Kobe University School of Medicine, Department of Obstetrics and Gynecology, Kobe (Japan); Okunaga, Takashi; Kubo, Kazuhiro [Kobe University Hospital, Department of Radiology Division, Kobe (Japan); Kanda, Tomonori [Teikyo University School of Medicine, Department of Radiology, Tokyo (Japan); Tamaki, Yukihisa [Shimane University School of Medicine, Department of Radiation Oncology, Shimane (Japan)
2015-07-15
To evaluate the usefulness of metabolic parameters obtained by {sup 18}F-FDG PET/CT for preoperative stratification of high-risk and low-risk endometrial carcinomas. Preoperative {sup 18}F-FDG PET/CT was performed in 56 women with endometrial cancer. Maximum standardized uptake values (SUVmax), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) of primary tumours were compared with clinicopathological features of surgical specimens. Diagnostic performance in terms of differentiation of low-risk disease (endometrioid histology, histological grade 1 or 2, invasion of less than half of the myometrium, and FIGO stage I) from high-risk disease was assessed. MTV and TLG were significantly higher in patients with higher histological grade (p = 0.0026 and p = 0.034), larger tumour size (p = 0.002 and p = 0.0017), lymphovascular space involvement (LVSI; p = 0.012 and p = 0.0051), myometrial invasion (p = 0.027 and p = 0.031), cervical stromal invasion (p = 0.023 and p = 0.014), ovarian metastasis (p = 0.00022 and p = 0.00034), lymph node metastasis (p < 0.0001 and p < 0.0001), and higher FIGO stage (p = 0.0011 and p = 0.00048). SUVmax was significantly higher in patients with larger tumour size (p = 0.0025), LVSI (p = 0.00023) and myometrial invasion (p < 0.0001). The areas under the ROC curves (AUCs) for distinguishing high-risk from low-risk carcinoma were 0.625, 0.829 and 0.797 for SUVmax, MTV and TLG, respectively. AUCs for both MTV and TLG were significantly larger than that for SUVmax (p = 0.0049 and p = 0.021). The optimal TLG cut-off value of 70.2, determined by ROC analysis, was found to have 72.0 % sensitivity and 74.2 % specificity for risk stratification. MTV and TLG of primary endometrial cancer show better correlations with clinicopathological features and are more useful for differentiating high-risk from low-risk carcinoma than SUVmax. (orig.)
ER and PR expression and survival after endometrial cancer.
Smith, Deborah; Stewart, Colin J R; Clarke, Edward M; Lose, Felicity; Davies, Claire; Armes, Jane; Obermair, Andreas; Brennan, Donal; Webb, Penelope M; Nagle, Christina M; Spurdle, Amanda B
2018-02-01
To measure association between endometrial carcinoma ER and PR status and endometrial cancer (EC) survival, accounting for inter-observer variation. The intensity and proportion of tumor cell expression of ER and PR in ECs were assessed independently and semi-quantitatively by two pathologists using digital images of duplicate tumor tissue microarrays (TMAs). Cases with inconsistent initial assessment were reviewed and final scoring agreed. The association between overall and EC-specific survival and hormone receptor expression (intensity, proportion and combined) was assessed using Cox regression analysis. The C-index was used to evaluate model discrimination with addition of ER and PR status. Tumor ER and PR analysis was possible in 659 TMAs from 255 patients, and in 459 TMAs from 243 patients, respectively. Initial ER and PR scoring was consistent in 82% and 80% of cases, respectively. In multivariate analyses decreased ER and PR expression was associated with increased tumor-related mortality. Associations reached statistical significance for ER proportion score (P=0.05), ER intensity score (P=0.003), and PR combined score (P=0.04). Decreased expression of combined ER/PR expression was associated with poorer EC-specific survival than decreased expression of either hormone receptor alone (P=0.005). However, hormone receptor status did not significantly improve mortality prediction in individual cases. ER and PR expression combined, using cut-points that capture variation in scoring and across cores, is significantly associated with EC-specific survival in analyses adjusting for known prognostic factors. However, at the individual level, ER and PR expression does not improve mortality prediction. Copyright © 2017 Elsevier Inc. All rights reserved.
Zhang, Hui; Li, Hongyan; Qi, Shasha; Liu, Zhao; Fu, Yibing; Li, Mingjiang; Zhao, Xingbo
2017-01-01
Stroma-tumor communication participates in the pathogenesis of endometrial carcinomas. In previous studies, we found that normal stromal cells inhibited the growth of endometrial carcinoma cells. Here, we investigated the role of normal stromal cells in the epithelial-mesenchymal transition (EMT) of endometrial carcinoma cells and explored the possible mechanism implied. We found that conditioned medium (CM) by normal endometrial stromal cells (NSC) reduced cell growth and induced cell apoptosis in Ishikawa cells. CM by NSC inhibited 17β-estradiol-induced cell growth and apoptosis decrease in Ishikawa cells. Moreover, CM by NSC inhibited the migration and invasion, and 17β-estradiol-induced migration and invasion in Ishikawa cells. Meanwhile, CM by NSC decreased Slug expression and 17β-estradiol-induced Slug expression, increased E-cadherin expression and abolished 17β-estradiol-induced E-cadherin reduction in Ishikawa cells. In conclusion, normal stromal factors can inhibit 17β-estradiol-induced cell proliferation and apoptosis inhibition, and abolished 17β-estradiol-induced EMT in endometrial cancer cell via regulating E-cadherin and Slug expression.
Leitao, Mario M; Malhotra, Vivek; Briscoe, Gabriel; Suidan, Rudy; Dholakiya, Priyal; Santos, Kevin; Jewell, Elizabeth L; Brown, Carol L; Sonoda, Yukio; Abu-Rustum, Nadeem R; Barakat, Richard R; Gardner, Ginger J
2013-10-01
Laparoscopy (LSC) offers superior patient outcomes compared to laparotomy. Small retrospective/prospective series have suggested robotics offers further reduction in postoperative pain and pain medication use compared to standard LSC. Our objective was to compare postoperative pain in patients undergoing robotically assisted (RBT) versus standard LSC for newly diagnosed endometrial cancer. All preoperative endometrial cancer cases scheduled for RBT and LSC from May 1, 2007 to June 9, 2010 were identified. For this analysis, we only included cases not requiring conversion to laparotomy. All patients were offered intravenous (IV) patient-controlled analgesia (PCA) postoperatively. Intraoperative equivalent fentanyl doses (IEFDs) and pain scores in the postanesthesia care unit (PACU) were assessed. IV PCA was used in 206 RBTs (86 %) and 208 LSCs (88 %). Median IEFD was 425 μg for LSCs and 500 μg for RBTs (P = 0.03). Median pain scores on PACU arrival were similar in both groups. Median highest pain score was 5 for LSCs and 4 for RBTs (P = 0.007). Linear regression demonstrated that the IEFD was not correlated with the highest pain score (R = 0.09; P = 0.07). Fentanyl was used postoperatively in 196 of 206 RBTs (95 %) and 187 of 208 LSCs (90 %). The total fentanyl doses were 242.5 (range 0-2705) μg and 380 (range 0-2625) μg, respectively (P multiple regression analysis further demonstrated RBT was independently associated with a lower total fentanyl dose compared to LSC (P = 0.02). RBT is independently associated with significantly lower postoperative pain and pain medication requirements compared to LSC. The amount of intraoperative fentanyl analgesia does not appear to correlate with postoperative pain.Endometrial cancer is the most common gynecologic malignancy in the United States, with an estimated 47,130 new cases in 2012.1 An estimated 287,100 women were diagnosed with endometrial cancer worldwide in 2008.2 Surgery is the primary treatment of choice for the
Lymph Node Assessment in Endometrial Cancer: Towards Personalized Medicine
Directory of Open Access Journals (Sweden)
Fabien Vidal
2013-01-01
Full Text Available Endometrial cancer (EC is the most common malignancy of the female reproductive tract and is increasing in incidence. Lymphovascular invasion and lymph node (LN status are strong predictive factors of recurrence. Therefore, the determination of the nodal status of patients is mandatory to optimally tailor adjuvant therapies and reduce local and distant recurrences. Imaging modalities do not yet allow accurate lymph node staging; thus pelvic and aortic lymphadenectomies remain standard staging procedures. The clinical data accumulated recently allow us to define low- and high-risk patients based on pre- or peroperative findings that will allow the clinician to stratify the patients for their need of lymphadenectomies. More recently, several groups have been introducing sentinel node mapping with promising results as an alternative to complete lymphadenectomy. Finally, the use of peroperative algorithm for risk determination could improve patient's staging with a reduction of lymphadenectomy-related morbidity.
PHENOTYPIC FEATURES OF ENDOMETRIAL CANCER AND MSI IN COLON AND BLOOD SERUM
Directory of Open Access Journals (Sweden)
S. M. Kartashov
2014-04-01
variation statistics methods using the χ2 criterion. Results. Estimation of MSI occurrence frequency in the colon tissue showed that MSI- colonic tissue is significantly more frequent (93.9 % compared to MSI+ (6.1 %, p<0.01. Analysis of MSI occurrence frequency in case of EC showed that MSI is significantly more frequently observed in blood serum (10.8 % of cases than in the colonic tissue (mucosal lining (6.1 %. A similar pattern was observed also in cases with MSI+ tumour phenotype (MSI frequency in colonic mucosal lining made 12.2 %, whereas in blood serum – 29.6 %, p <0.01. Analysis of indices in cases with MSI- tumour phenotype demonstrated inverse relation, i.e. genome microsatellite instability was more frequently observed in the colonic mucosal lining than in blood serum (p<0.05. We have carried out analysis of the MSI occurrence frequency in colonic tissue depending on the EC phenotypic traits and risk factors. The obtained data on the MSI disorder occurrence frequency in colonic tissue in case of EC depending on the endometrial carcinoma risk factors demonstrated correlation with the majority of criteria, thus verifying the literature data on the presence of common pathogenetic mechanisms in case of EC and colon cancer. Conclusions. 1. MSI disorders in the colonic mucosal lining and blood serum are more frequently observed in case of EC MSI + phenotype. 2. Similarity of pathogenesis in terms of EC and colon cancer is affected by similar phenotypic traits of patients as well as by MSI development.
Molecular Biology and Prevention of Endometrial Cancer. Addendum
National Research Council Canada - National Science Library
Maxwell, George L
2008-01-01
Objective: To increase our understanding of the molecular aberrations associated with endometrial carcinogenesis and the biologic mechanisms underlying the protective effect of oral contraceptive (OC) therapy. Methods: 1...
Usefulness of MRI in diagnosis of endometrial carcinoma and endometrial hyperplasia
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Kasai, Mayumi; Moriai, Kayo; Murai, Shinya; Imai, Toshihiko; Iida, Hajime; Suzuki, Hiroshi (Iwate Prefectural Central Hospital, Morioka (Japan))
1994-06-01
The study was to assess the usefulness of T2-weighted and enhanced T1-weighted MR images in differentiating endometrial adenocarcinoma and hyperplasia. The subjects were 21 patients with endometrial hyperplasia (Group A), consisting of 15 with cystic glandular hyperplasia and 6 with atypical hyperplasia, and 7 with endometrial adenocarcinoma (Group B). Six other patients with no evidence of abnormal endometrial findings served as controls. In Group A, the endometrium had a high signal intensity on T2-weighted images, and was 10 mm or over in thickness before menopause and 6 mm after menopause. It was also a high or intermediate signal intensity on enhanced T1-weighted images. In patiemts with cystic glandular hyperplasia, the junctional zone was 10 mm or over on T2-weighted images. Similar findings were seen on enhanced T1-weighted images. In patients with atypical hyperplasia, the junctional zone disappeared or decreased on enhanced images compared with those on T2-weighted images. In group B, the endometrium had an intermediate or high signal intensity on T2-weighted images, with the junctional zone being 10 mm or more. Enhanced T1-weighted images showed lower signal intensities in the tumorous area than in the normal endometrium and muscular layer. These findings indicated that enhanced MR imaging may be useful in diagnosing endometrial lesions. (N.K.).
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Lin, Gigin; Lu, Hsin-Ying [Chang Gung Memorial Hospital at Linkou and Chang Gung University, Department of Medical Imaging and Intervention, Institute for Radiological Research, Guishan, Taoyuan (China); Chang Gung Memorial Hospital at Linkou, Clinical Phenome Center, Guishan, Taoyuan (China); Huang, Yu-Ting; Lin, Yu-Chun; Ng, Shu-Hang; Ng, Koon-Kwan [Chang Gung Memorial Hospital at Linkou and Chang Gung University, Department of Medical Imaging and Intervention, Institute for Radiological Research, Guishan, Taoyuan (China); Chao, Angel; Lai, Chyong-Huey [Chang Gung Memorial Hospital at Linkou and Chang Gung University, Department of Obstetrics and Gynecology and Gynecologic Cancer Research Center, Guishan, Taoyuan (China); Yang, Lan-Yan [Chang Gung Memorial Hospital at Linkou and Chang Gung University, Clinical Trial Center, Guishan, Taoyuan (China); Wu, Ren-Chin [Chang Gung Memorial Hospital at Linkou and Chang Gung University, Department of Pathology, Guishan, Taoyuan (China)
2017-05-15
To compare the diagnostic accuracy of diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) magnetic resonance (MR) imaging for detecting cervical stromal invasion in endometrial cancer. Eighty-three consecutive women with endometrial cancer underwent preoperative evaluation in a 3-T unit, including T2-weighted, DW (b = 0 and 1000 s/mm{sup 2}), and DCE MR imaging. Two radiologists independently assessed presence of cervical stromal invasion, with histopathological reference as gold standard. For assessing cervical stromal invasion, the diagnostic accuracy, sensitivity, and specificity, respectively for Reader 1/Reader 2, were as follows: DW MR imaging - 95.2 %/91.6 %, 91.7 %/100 %, and 95.8 %/90.1 %; DCE MR imaging - 91.6 %/88 %, 58.3 %/50 %, and 97.2 %/94.4 %. The diagnostic performance of DW MR imaging (Reader 1: areas under the receiver operating characteristic curve (AUC) = 0.98; Reader 2: AUC = 0.97) was significantly higher than that of DCE MR imaging (p = 0.009 for Reader 2) or T2-weighted MR imaging (Reader 1: p = 0.006; Reader 2: p = 0.013). Patients with cervical stromal invasion showed a significantly greater canal width (p < 0.0001) and myometrial invasion extent (p = 0.006). DW MR imaging has superior diagnostic performance compared with DCE MR imaging in the detection of cervical stromal invasion. (orig.)
POLE proofreading mutations elicit an anti-tumor immune response in endometrial cancer
van Gool, Inge C; Eggink, Florine A; Freeman-Mills, Luke; Stelloo, Ellen; Marchi, Emanuele; de Bruyn, Marco; Palles, Claire; Nout, Remi A; de Kroon, Cor D; Osse, Elisabeth M; Klenerman, Paul; Creutzberg, Carien L; Tomlinson, Ian PM; Smit, Vincent THBM; Nijman, Hans W
2015-01-01
Purpose Recent studies have shown that 7-12% of endometrial cancers (ECs) are ultramutated due to somatic mutation in the proofreading exonuclease domain of the DNA replicase POLE. Interestingly, these tumors have an excellent prognosis. In view of the emerging data linking mutation burden, immune response and clinical outcome in cancer, we investigated whether POLE-mutant ECs showed evidence of increased immunogenicity. Experimental design We examined immune infiltration and activation according to tumor POLE proofreading mutation in a molecularly defined EC cohort including 47 POLE-mutant tumors. We sought to confirm our results by analysis of RNAseq data from the TCGA EC series and used the same series to examine whether differences in immune infiltration could be explained by an enrichment of immunogenic neoepitopes in POLE-mutant ECs. Results Compared to other ECs, POLE-mutants displayed an enhanced cytotoxic T cell response, evidenced by increased numbers of CD8+ tumor infiltrating lymphocytes and CD8A expression, enrichment for a tumor-infiltrating T cell gene signature, and strong upregulation of the T cell cytotoxic differentiation and effector markers T-bet, Eomes, IFNG, PRF and granzyme B. This was accompanied by upregulation of T cell exhaustion markers, consistent with chronic antigen exposure. In-silico analysis confirmed that POLE-mutant cancers are predicted to display more antigenic neo-epitopes than other ECs, providing a potential explanation for our findings. Conclusions Ultramutated POLE proofreading-mutant ECs are characterized by a robust intratumoral T cell response, which correlates with, and may be caused by an enrichment of antigenic neo-peptides. Our study provides a plausible mechanism for the excellent prognosis of these cancers. PMID:25878334
Germline truncating-mutations in BRCA1 and MSH6 in a patient with early onset endometrial cancer
International Nuclear Information System (INIS)
Kast, Karin; Schackert, Hans K; Neuhann, Teresa M; Görgens, Heike; Becker, Kerstin; Keller, Katja; Klink, Barbara; Aust, Daniela; Distler, Wolfgang; Schröck, Evelin
2012-01-01
Hereditary Breast and Ovarian Cancer Syndrome (HBOCS) and Hereditary Non-Polyposis Colorectal Cancer Syndrome (HNPCC, Lynch Syndrome) are two tumor predisposition syndromes responsible for the majority of hereditary breast and colorectal cancers. Carriers of both germline mutations in breast cancer genes BRCA1 or BRCA2 and in mismatch repair (MMR) genes MLH1, MSH2, MSH6 or PMS2 are very rare. We identified germline mutations in BRCA1 and in MSH6 in a patient with increased risk for HBOC diagnosed with endometrial cancer at the age of 46 years. Although carriers of mutations in both MMR and BRCA genes are rare in Caucasian populations and anamnestical and histopathological findings may guide clinicians to identify these families, both syndromes can only be diagnosed through a complete gene analysis of the respective genes
Germline truncating-mutations in BRCA1 and MSH6 in a patient with early onset endometrial cancer
Energy Technology Data Exchange (ETDEWEB)
Kast, Karin [Department of Gynecology and Obstetrics, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden (Germany); Schackert, Hans K [Department of Surgical Research, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden (Germany); Neuhann, Teresa M [Institute for Clinical Genetics, Technische Universität Dresden, Dresden (Germany); Medical Genetic Center, Munich (Germany); Görgens, Heike [Department of Surgical Research, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden (Germany); Becker, Kerstin [Institute for Clinical Genetics, Technische Universität Dresden, Dresden (Germany); Keller, Katja [Department of Gynecology and Obstetrics, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden (Germany); Klink, Barbara [Institute for Clinical Genetics, Technische Universität Dresden, Dresden (Germany); Aust, Daniela [Institute of Pathology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden (Germany); Distler, Wolfgang [Department of Gynecology and Obstetrics, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden (Germany); Schröck, Evelin [Institute for Clinical Genetics, Technische Universität Dresden, Dresden (Germany)
2012-11-20
Hereditary Breast and Ovarian Cancer Syndrome (HBOCS) and Hereditary Non-Polyposis Colorectal Cancer Syndrome (HNPCC, Lynch Syndrome) are two tumor predisposition syndromes responsible for the majority of hereditary breast and colorectal cancers. Carriers of both germline mutations in breast cancer genes BRCA1 or BRCA2 and in mismatch repair (MMR) genes MLH1, MSH2, MSH6 or PMS2 are very rare. We identified germline mutations in BRCA1 and in MSH6 in a patient with increased risk for HBOC diagnosed with endometrial cancer at the age of 46 years. Although carriers of mutations in both MMR and BRCA genes are rare in Caucasian populations and anamnestical and histopathological findings may guide clinicians to identify these families, both syndromes can only be diagnosed through a complete gene analysis of the respective genes.
Germline truncating-mutations in BRCA1 and MSH6 in a patient with early onset endometrial cancer.
Kast, Karin; Neuhann, Teresa M; Görgens, Heike; Becker, Kerstin; Keller, Katja; Klink, Barbara; Aust, Daniela; Distler, Wolfgang; Schröck, Evelin; Schackert, Hans K
2012-11-20
Hereditary Breast and Ovarian Cancer Syndrome (HBOCS) and Hereditary Non-Polyposis Colorectal Cancer Syndrome (HNPCC, Lynch Syndrome) are two tumor predisposition syndromes responsible for the majority of hereditary breast and colorectal cancers. Carriers of both germline mutations in breast cancer genes BRCA1 or BRCA2 and in mismatch repair (MMR) genes MLH1, MSH2, MSH6 or PMS2 are very rare. We identified germline mutations in BRCA1 and in MSH6 in a patient with increased risk for HBOC diagnosed with endometrial cancer at the age of 46 years. Although carriers of mutations in both MMR and BRCA genes are rare in Caucasian populations and anamnestical and histopathological findings may guide clinicians to identify these families, both syndromes can only be diagnosed through a complete gene analysis of the respective genes.
Estrogen and high-fat diet induced alterations in C57BL/6 mice endometrial transcriptome profile
Directory of Open Access Journals (Sweden)
Yali Cheng
2017-12-01
Full Text Available Unopposed estrogen stimulation and insulin resistance are known to play important roles in endometrial cancer (EC, but the interaction between these two factors and how they contribute to endometrial lesions are not completely elucidated. To investigate the endometrial transcriptome profile and the associated molecular pathway alterations, we established an ovariectomized C57BL/6 mouse model treated with subcutaneous implantation of 17-β estradiol (E2 pellet and/or high-fat diet (HFD for 12 weeks to mimic sustained estrogen stimulation and insulin resistance. Histomorphologically, we found that both E2 and E2 + HFD groups showed markedly enlarged uterus and increased number of endometrial glands. The endometrium samples were collected for microarray assay. GO and KEGG analysis showed that genes regulated by E2 and/or HFD are mainly responsible for immune response, inflammatory response and metabolic pathways. Further IPA analysis demonstrated that the acute phase response signaling, NF-κB signaling, leukocyte extravasation signaling, PPAR signaling and LXR/RXR activation pathways are mainly involved in the pathways above. In addition, the genes modulated reciprocally by E2 and/or HFD were also analyzed, and their crosstalk mainly focuses on enhancing one another’s activity. The combination analysis of microarray data and TCGA database provided potential diagnostic or therapeutic targets for EC. Further validation was performed in mice endometrium and human EC cell lines. In conclusion, this study unraveled the endometrial transcriptome profile alterations affected by E2 and/or HFD that may disturb endometrial homeostasis and contribute to the development of endometrial hyperplasia.
Adjuvant high dose rate vaginal cuff brachytherapy for early stage endometrial cancer
International Nuclear Information System (INIS)
Tannehill, S.P.; Petereit, D.G.; Schink, J.C.; Grosen, E.A.; Hartenbach, E.M.; Thomadsen, B.R.; Buchler, D.A.
1997-01-01
Objective: To determine the efficacy and complications of adjuvant high dose rate (HDR) vaginal cuff brachytherapy (VCB) in patients (pts) with low risk endometrial carcinoma. Materials and Methods: Since 1989, 154 patients were treated with outpatient adjuvant VCB for low risk endometrial cancer (Stage IA-14%, Stage IB-82%). Four percent of patients with stage IC disease were treated with VCB only because of medical contraindications to pelvic radiation. Patients had the following histologic grades: 53% grade 1, 40% grade 2, 5% grade 3 and 3% unknown (99%-adenocarcinoma, <1% papillary serous histology). Seventy-three percent of patients had their surgery (TAH-BSO) performed at an outside institution with minimal surgical assessment of the lymph nodes. At a median of 6 weeks after surgery, patients were treated with 2 HDR VCB insertions delivered 1 week apart. Ovoids were placed at the vaginal apex to deliver 16.2 Gy per fraction to the vaginal surface (LDR equivalent of 60 Gy at 100 cGy/h) under conscious outpatient sedation. All clinical endpoints were calculated using the Kaplan Meier method. Complications were scored using the RTOG 5-tiered system. Results: The median time in the brachytherapy suite was 60 minutes with no acute complications observed. With a median follow-up of 33 months (3-79 months), the 4-year overall and disease-free survival were 93% and 96% respectively. Five patients (3%) recurred: 2 intra-abdominally, 1 with lung metastases, and 2 in the pelvic lymph nodes. There were no vaginal cuff recurrences. The single patient with an isolated pelvic sidewall recurrence was salvaged with pelvic RT. Six patients developed a small area of asymptomatic necrosis at the vaginal cuff, which spontaneously healed at a median time of 4 months. There were no grade 3 or greater late tissue toxicities. No patient experienced significant vaginal stenosis, with 20% of the patients experiencing mild fibrosis of the vaginal apex. Conclusions: Adjuvant HDR VCB in 2
DEFF Research Database (Denmark)
Vilstrup, Mie Holm; Jochumsen, Kirsten M; Hess, Søren
2017-01-01
.19-8.49) and 1.93 (0.80-4.68), respectively. Whole-body cTLG of greater than or equal to 176.1 g yielded a hazard ratio of 5.70 (1.94-16.78) for OS in a multivariate analysis. CONCLUSIONS: Preoperative SUVmax and cTLG showed potential as independent prognostic markers of OS in patients with primarily high...... and a preoperative F-fluorodeoxyglucose positron emission tomography/computed tomography before curatively intended treatment were included. The scans were evaluated using standard uptake values [maximum standard uptake value (SUVmax) and partial volume corrected (c) mean standardized uptake value (SUVmean...... proportional regression models were used for prognostic evaluation. RESULTS: Eighty-three patients (median age, 69.9 y; range, 26.8-91.1) with primarily high-risk endometrial cancer or suspected high The International Federation of Gynecology and Obstetrics stage were included. Mean follow-up time was 3...
Germline truncating-mutations in BRCA1 and MSH6 in a patient with early onset endometrial cancer
Directory of Open Access Journals (Sweden)
Kast Karin
2012-11-01
Full Text Available Abstract Background Hereditary Breast and Ovarian Cancer Syndrome (HBOCS and Hereditary Non-Polyposis Colorectal Cancer Syndrome (HNPCC, Lynch Syndrome are two tumor predisposition syndromes responsible for the majority of hereditary breast and colorectal cancers. Carriers of both germline mutations in breast cancer genes BRCA1 or BRCA2 and in mismatch repair (MMR genes MLH1, MSH2, MSH6 or PMS2 are very rare. Case presentation We identified germline mutations in BRCA1 and in MSH6 in a patient with increased risk for HBOC diagnosed with endometrial cancer at the age of 46 years. Conclusions Although carriers of mutations in both MMR and BRCA genes are rare in Caucasian populations and anamnestical and histopathological findings may guide clinicians to identify these families, both syndromes can only be diagnosed through a complete gene analysis of the respective genes.
Role of pelvic lymphadenectomy in stage 1A endometrial carcinoma ...
African Journals Online (AJOL)
Introduction: Endometrial cancer is the commonest gynecological cancer mostly affecting women in the postmenopausal age group. There is a debate regarding the need of pelvic lymphadenectomy in managing stage 1A diagnosed preoperatively, we try to evaluate this need. Objective: To evaluate the role of pelvic ...
[Establishment of mouse endometrial injury model by electrocoagulation].
Hu, Xiaoxiao; Lin, Xiaona; Jiang, Yinshen; Shi, Libing; Wang, Jieyu; Zhao, Lijuan; Zhang, Songying
2014-12-23
To establish the murine model of moderate endometrial injury. Electrocoagulation was applied to induce endometrial injury of ICR mice with 0.5 watts power while contralateral uterine cavity acted as control without electrocoagulation. The endometrial histomorphology was observed in 7 days later by microscopy and fetal number of each lateral uterus assessed at 17.5 days after pregnancy. At 7 days post-electrocoagulation, the average endometrial thickness of operating side was significantly thinner than that of control side (1.14 ± 0.08 vs 1.88 ± 0.15 mm, P electrocoagulation injury shows morphologic changes and decreased fertile ability. It has potential uses for animal studies of endometrial injury treatment.
Nogami, Yuya; Banno, Kouji; Irie, Haruko; Iida, Miho; Kisu, Iori; Masugi, Yohei; Tanaka, Kyoko; Tominaga, Eiichiro; Okuda, Shigeo; Murakami, Koji; Aoki, Daisuke
2015-01-01
We studied the diagnostic performance of (18)F-fluoro-2-deoxy-d-glucose-positron emission tomography/computed tomography in cervical and endometrial cancers with particular focus on lymph node metastases. Seventy patients with cervical cancer and 53 with endometrial cancer were imaged with (18)F-fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography before lymphadenectomy. We evaluated the diagnostic performance of (18)F-fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography using the final pathological diagnoses as the golden standard. We calculated the sensitivity, specificity, positive predictive value and negative predictive value of (18)F-fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography. In cervical cancer, the results evaluated by cases were 33.3, 92.7, 55.6 and 83.6%, respectively. When evaluated by the area of lymph nodes, the results were 30.6, 98.9, 55.0 and 97.0%, respectively. As for endometrial cancer, the results evaluated by cases were 50.0, 93.9, 40.0 and 95.8%, and by area of lymph nodes, 45.0, 99.4, 64.3 and 98.5%, respectively. The limitation of the efficacy was found out by analyzing it by the region of the lymph node, the size of metastatic node, the historical type of tumor in cervical cancer and the prevalence of lymph node metastasis. The efficacy of positron emission tomography/computed tomography regarding the detection of lymph node metastasis in cervical and endometrial cancer is not established and has limitations associated with the region of the lymph node, the size of metastasis lesion in lymph node and the pathological type of primary tumor. The indication for the imaging and the interpretation of the results requires consideration for each case by the pretest probability based on the information obtained preoperatively. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Taylor, S E; Cheung, K T; Patel, I I; Trevisan, J; Stringfellow, H F; Ashton, K M; Wood, N J; Keating, P J; Martin-Hirsch, P L; Martin, F L
2011-03-01
Endometrial cancer is the most common gynaecological malignancy in the United Kingdom. Diagnosis currently involves subjective expert interpretation of highly processed tissue, primarily using microscopy. Previous work has shown that infrared (IR) spectroscopy can be used to distinguish between benign and malignant cells in a variety of tissue types. Tissue was obtained from 76 patients undergoing hysterectomy, 36 had endometrial cancer. Slivers of endometrial tissue (tumour and tumour-adjacent tissue if present) were dissected and placed in fixative solution. Before analysis, tissues were thinly sliced, washed, mounted on low-E slides and desiccated; 10 IR spectra were obtained per slice by attenuated total reflection Fourier-transform IR (ATR-FTIR) spectroscopy. Derived data was subjected to principal component analysis followed by linear discriminant analysis. Post-spectroscopy analyses, tissue sections were haematoxylin and eosin-stained to provide histological verification. Using this approach, it is possible to distinguish benign from malignant endometrial tissue, and various subtypes of both. Cluster vector plots of benign (verified post-spectroscopy to be free of identifiable pathology) vs malignant tissue indicate the importance of the lipid and secondary protein structure (Amide I and Amide II) regions of the spectrum. These findings point towards the possibility of a simple objective test for endometrial cancer using ATR-FTIR spectroscopy. This would facilitate earlier diagnosis and so reduce the morbidity and mortality associated with this disease.
Concurrent Endometrial Carcinosarcoma and Thyroid Papillary Carcinoma: PET CT Imaging Findings
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Mine Genc
2015-06-01
Full Text Available The aim of this study is to report a patient who was diagnosed with a concurrent primary tumor by 18-fluoro-2-deoxy-glucose positron emission tomography (FDG PET imaging performed for staging of an endometrial cancer. FDG uptake was detected in the uterus, where the primary cancer was located, and in the left lobe of the thyroid gland. The biopsy sample from the hypermetabolic nodular lesion in thyroid gland revealed intermediate cytology according to Bethesda Classification. The patient underwent hysterectomy and thyroidectomy. An endometrial carcinoma in the uterus and a multicentric thyroid papillary carcinoma in the thyroid gland were diagnosed.
Seidelin, Ulla Holten; Ibfelt, Else; Andersen, Ingelise; Steding-Jessen, Marianne; Høgdall, Claus; Kjær, Susanne Krüger; Dalton, Susanne Oksbjerg
2016-06-01
Several studies have documented an association between socioeconomic position and survival from gynaecological cancer, but the mechanisms are unclear. The aim of this study was to examine the association between level of education and survival after endometrial cancer among Danish women; and whether differences in stage at diagnosis and comorbidity contribute to the educational differences in survival. Women with endometrial cancer diagnosed between 2005 and 2009 were identified in the Danish Gynaecological Cancer Database, with information on clinical characteristics, surgery, body mass index (BMI) and smoking status. Information on highest attained education, cohabitation and comorbidity was obtained from nationwide administrative registries. Logistic regression models were used to determine the association between level of education and cancer stage and Cox proportional hazards model for analyses of overall survival. Of the 3638 patients identified during the study period, 787 had died by the end of 2011. The group of patients with short education had a higher odds ratio (OR) for advanced stage at diagnosis, but this was not statistically significant (adjusted OR 1.20; 95% CI 0.97-1.49). The age-adjusted hazard ratio (HR) for dying of patients with short education was 1.47 (CI 95% 1.17-1.80). Adjustment for cohabitation status, BMI, smoking and comorbidity did not change HRs, but further adjustment for cancer stage yielded a HR of 1.36 (1.11-1.67). Early detection in all educational groups might reduce social inequalities in survival, however, the unexplained increased risk for death after adjustment for prognostic factors, warrants increased attention to patients with short education in all age groups throughout treatment and rehabilitation.
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Kavanagh Mary
2009-02-01
Full Text Available Abstract Background To examine the effects of a 6 month lifestyle intervention on quality of life, depression, self-efficacy and eating behavior changes in overweight and obese endometrial cancer survivors. Methods Early stage endometrial cancer survivors were randomized to intervention (n = 23 or usual care (n = 22 groups. Chi-square, Student's t-test and repeated measures analysis of variance were used in intent-to-treat analyses. Outcomes were also examined according to weight loss. Results Morbidly obese patients had significantly lower self-efficacy, specifically when feeling physical discomfort. There was a significant improvement for self-efficacy related to social pressure (p = .03 and restraint (p = .02 in the LI group. There was a significant difference for emotional well-being quality of life (p = .02, self-efficacy related to negative emotions (p Conclusion This pilot lifestyle intervention had no effect on quality of life or depression but did improve self-efficacy and some eating behaviors. Trial Registration http://www.clinicaltrials.gov; NCT00420979
Hanlon, Alexandra; Small, William; Strauss, Jonathan; Lin, Lilie L; Hanisch, Laura; Huang, Liming; Bai, Jinbing; Wells, Jessica; Bruner, Deborah Watkins
Vaginal brachytherapy, a common treatment of endometrial cancer, is associated with high rates of vaginal stenosis. Recommendations for vaginal dilator use to minimize stenosis generally include 3 times per week for approximately 10 minutes per use. However, adherence rates range widely and are generally well less than 50%. The aims of this study were to assess feasibility of recruitment to a study of dilator use and test a theoretically driven enhanced educational program (EEP) to increase adherence. Eligibility included women treated with postoperative vaginal brachytherapy for stage I to IIIc endometrial cancer. Patients were randomized to either nurse-delivered standard institutional instruction or EEP. Of eligible patients, 76% consented, 42 were randomized, and 69% completed the 6-month assessment. Mean age was 58.2 years; 48% were sexually active. There was no difference in adherence between arms. Overall, 20% and 8.3% were adherent to the prescribed use of 3 times per week, and 64% and 16% were adherent to use at least once per week at 6 weeks and 6 months, respectively. Adherence was greater among those motivated by vaginal health and having lower body mass index. Nonadherence was significantly higher among those who are college educated, in the EEP group, and with higher weight. Feasibility of recruitment into a study of vaginal dilator use was high. Adherence was low, and there was no difference between groups. Adherence to vaginal dilator use requires novel interventions to test. Nursing education that includes how dilators may maintain vaginal health may improve use because it was a motivator for adherence in this study.
Metcalf, Alexander M; Spurdle, Amanda B
2014-03-01
Colorectal cancer (CRC) that displays high microsatellite instability (MSI-H) can be caused by either germline mutations in mismatch repair (MMR) genes, or non-inherited transcriptional silencing of the MLH1 promoter. A correlation between MLH1 promoter methylation, specifically the 'C' region, and BRAF V600E status has been reported in CRC studies. Germline MMR mutations also greatly increase risk of endometrial cancer (EC), but no systematic review has been undertaken to determine if these tumour markers may be useful predictors of MMR mutation status in EC patients. Endometrial cancer cohorts meeting review inclusion criteria encompassed 2675 tumours from 20 studies for BRAF V600E, and 447 tumours from 11 studies for MLH1 methylation testing. BRAF V600E mutations were reported in 4/2675 (0.1%) endometrial tumours of unknown MMR mutation status, and there were 7/823 (0.9%) total sequence variants in exon 11 and 27/1012 (2.7%) in exon 15. Promoter MLH1 methylation was not observed in tumours from 32 MLH1 mutation carriers, or for 13 MSH2 or MSH6 mutation carriers. MMR mutation-negative individuals with tumour MLH1 and PMS2 IHC loss displayed MLH1 methylation in 48/51 (94%) of tumours. We have also detailed specific examples that show the importance of MLH1 promoter region, assay design, and quantification of methylation. This review shows that BRAF mutations occurs so infrequently in endometrial tumours they can be discounted as a useful marker for predicting MMR-negative mutation status, and further studies of endometrial cohorts with known MMR mutation status are necessary to quantify the utility of tumour MLH1 promoter methylation as a marker of negative germline MMR mutation status in EC patients.
International Nuclear Information System (INIS)
Chitcholtan, Kenny; Asselin, Eric; Parent, Sophie; Sykes, Peter H.; Evans, John J.
2013-01-01
Three-dimensional (3D) in vitro models have an invaluable role in understanding the behaviour of tumour cells in a well defined microenvironment. This is because some aspects of tumour characteristics cannot be fully recapitulated in a cell monolayer (2D). In the present study, we compared growth patterns, expression of signalling molecules, and metabolism-associated proteins of endometrial cancer cell lines in 3D and 2D cell cultures. Cancer cells formed spherical structures in 3D reconstituted basement membrane (3D rBM), and the morphological appearance was cell line dependent. Cell differentiation was observed after 8 days in the 3D rBM. There was reduced proliferation, detected by less expression of PCNA in 3D rBM than in 2D cell monolayers. The addition of exogenous epidermal growth factor (EGF) to cancer cells induced phosphorylation of EGFR and Akt in both cell culture conditions. The uptake of glucose was selectively altered in the 3D rBM, but there was a lack of association with Glut-1 expression. The secretion of vascular endothelial growth factor (VEGF) and prostaglandin E 2 (PGE 2 ) was selectively altered in 3D rBM, and it was cell line dependent. Our data demonstrated that 3D rBM as an in vitro model can influence proliferation and metabolism of endometrial cancer cell behaviour compared to 2D cell monolayer. Changes are specific to individual cell types. The use of 3D rBM is, therefore, important in the in vitro study of targeted anticancer therapies.
Energy Technology Data Exchange (ETDEWEB)
Chitcholtan, Kenny, E-mail: kenny.chitcholtan@otago.ac.nz [Department of Obstetrics and Gynaecology, University of Otago, Christchurch, 2 Riccarton Avenue, Christchurch 8011 (New Zealand); Asselin, Eric, E-mail: Eric.Asselin@uqtr.ca [Department of Chemistry and Biology, University of Quebec, at Trois-Rivières, C.P. 500, Trois-Rivières, Quebec, Canada G9A 5H7 (Canada); Parent, Sophie, E-mail: Sophie.Parent@uqtr.ca [Department of Chemistry and Biology, University of Quebec, at Trois-Rivières, C.P. 500, Trois-Rivières, Quebec, Canada G9A 5H7 (Canada); Sykes, Peter H., E-mail: peter.sykes@otago.ac.nz [Department of Obstetrics and Gynaecology, University of Otago, Christchurch, 2 Riccarton Avenue, Christchurch 8011 (New Zealand); Evans, John J., E-mail: john.evans@otago.ac.nz [Department of Obstetrics and Gynaecology, University of Otago, Christchurch, 2 Riccarton Avenue, Christchurch 8011 (New Zealand); Centre of Neuroendocrinology and The MacDiarmid Institute of Advanced Materials and Nanotechnology, University of Otago, Christchurch, 2 Riccarton Avenue, Christchurch 8011 (New Zealand)
2013-01-01
Three-dimensional (3D) in vitro models have an invaluable role in understanding the behaviour of tumour cells in a well defined microenvironment. This is because some aspects of tumour characteristics cannot be fully recapitulated in a cell monolayer (2D). In the present study, we compared growth patterns, expression of signalling molecules, and metabolism-associated proteins of endometrial cancer cell lines in 3D and 2D cell cultures. Cancer cells formed spherical structures in 3D reconstituted basement membrane (3D rBM), and the morphological appearance was cell line dependent. Cell differentiation was observed after 8 days in the 3D rBM. There was reduced proliferation, detected by less expression of PCNA in 3D rBM than in 2D cell monolayers. The addition of exogenous epidermal growth factor (EGF) to cancer cells induced phosphorylation of EGFR and Akt in both cell culture conditions. The uptake of glucose was selectively altered in the 3D rBM, but there was a lack of association with Glut-1 expression. The secretion of vascular endothelial growth factor (VEGF) and prostaglandin E{sub 2} (PGE{sub 2}) was selectively altered in 3D rBM, and it was cell line dependent. Our data demonstrated that 3D rBM as an in vitro model can influence proliferation and metabolism of endometrial cancer cell behaviour compared to 2D cell monolayer. Changes are specific to individual cell types. The use of 3D rBM is, therefore, important in the in vitro study of targeted anticancer therapies.
Modesitt, Susan C; Geffel, Dyanna L; Via, Jennifer; L Weltman, Arthur
2012-03-01
Exercise is potentially protective against cancer for obese women. The objectives were to examine differences in activity, body composition, and hormones in overweight/obese women with and without endometrial cancer. Women ≥ 50 years old with a body mass index (BMI) ≥ 25 kg/m(2) scheduled for abdominal hysterectomy were enrolled. Demographics, physical activity, and quality of life (QOL) data were collected. Body composition/fitness was evaluated using Air Displacement Plethysmography (BodPod) and a standardized treadmill. Adiponectin, androstenedione, leptin, estradiol, estrone, progesterone, sex hormone binding globulin, insulin and glucose were measured. Thirty-eight women enrolled in this pilot study; 22 had endometrial cancer. Mean age was 58.3 years, mean BMI, fat weight and percent body fat were 41.3 kg/m(2), 55 kg and 51% respectively. Fitness levels were poor; 90% of women had peak oxygen uptakes below the 10th percentile of population normals yet 80% still rated their fitness level as equivalent to other women. Women with and without cancer did not differ in age, BMI, co-morbidities, energy expenditures, body composition, hormones or QOL although glucose levels were higher in women with cancer (119.5 vs. 90.7 mg/dl; p=0.049). Cancer subjects scored worse on every fitness measurement, reaching statistical significance for VO(2 peak) (15.0 vs. 17.9 ml/kg/min; p=0.033). Current exercisers had a lower BMI (p=0.039), decreased fat weight (p=0.024), decreased waist circumference (p=0.05) and improved vitality compared to non-exercisers. Physical fitness levels were abysmal in these morbidly obese subjects and worse for cancer patients. Exercise correlated with improved body composition and vitality. Copyright © 2011. Published by Elsevier Inc.
The value of gynecologic cancer follow-up
DEFF Research Database (Denmark)
Lajer, Henrik; Jensen, Mette B.; Kilsmark, Jannie
2010-01-01
that follow-up affects the women's quality of life. CONCLUSIONS:: The main purpose of follow-up after treatment of cancer is improved survival. Our review of the literature showed no evidence of a positive effect on survival in women followed up after primary treatment of endometrial or ovarian cancer......INTRODUCTION:: To explore the extent of evidence-based data and cost-utility of follow-up after primary treatment of endometrial and ovarian cancer, addressing perspectives of technology, organization, economics, and patients. METHODS:: Systematic literature searches according......:: None of the identified studies supported a survival benefit from hospital-based follow-up after completion of primary treatment of endometrial or ovarian cancer. The methods for follow-up were of low technology (gynecologic examination with or without ultrasound examination). Other technologies had...
Della Badia, Carl; Karini, Homa
2010-01-01
Endometrial stromal sarcoma is a rare uterine cancer with no reliable method for preoperative diagnosis. A 30-year-old parous woman underwent laparoscopic supracervical hysterectomy because of a leiomyoma. The uterus was removed from the abdominal cavity with an electric morcellator with a spinning blade. The pathology report revealed low-grade endometrial stromal sarcoma. Two months after the initial surgery, a second laparoscopic procedure was performed. The final pathology report confirmed low-grade endometrial stromal sarcoma involving the ovary, fallopian tube, and ovarian artery. It was concluded that morcellation of leiomyomas at laparoscopic supracervical hysterectomy may potentially increase metastasis if the tumor is a sarcoma. Copyright © 2010 AAGL. Published by Elsevier Inc. All rights reserved.
Kato, Aya; Sato, Naoki; Sugawara, Tae; Takahashi, Kazue; Kito, Masahiko; Makino, Kenichi; Sato, Toshiharu; Shimizu, Dai; Shirasawa, Hiromitu; Miura, Hiroshi; Sato, Wataru; Kumazawa, Yukiyo; Sato, Akira; Kumagai, Jin; Terada, Yukihiro
2016-01-01
Lynch syndrome (LS) is an autosomal dominant inherited disorder mainly caused by a germline mutation in the DNA mismatch repair (MMR) genes (MLH1, MSH2, MSH6, PMS2) and is associated with increased risk of various cancers, particularly colorectal cancer and endometrial cancer (EC). Women with LS account for 2–6% of EC patients; it is clinically important to identify LS in such individuals for predicting and/or preventing additional LS-associated cancers. PMS2 germline mutation ...
Expression of epidermal growth factor receptors in human endometrial carcinoma
DEFF Research Database (Denmark)
Nyholm, H C; Nielsen, Anette Lynge; Ottesen, B
1993-01-01
Little data exist on the expression of epidermal growth factor receptors (EGF-Rs) in human endometrial cancer. EGF-R status was studied in 65 patients with endometrial carcinomas and in 26 women with nonmalignant postmenopausal endometria, either inactive/atrophic endometrium or adenomatous...... hyperplasia. EGF-R was identified on frozen tissue sections by means of an indirect immunoperoxidase technique with a monoclonal antibody against the external domain of the EGF-R. Seventy-one percent of the carcinomas expressed positive EGF-R immunoreactivity. In general, staining was most prominent...
Johnatty, Sharon E; Tan, Yen Y; Buchanan, Daniel D; Bowman, Michael; Walters, Rhiannon J; Obermair, Andreas; Quinn, Michael A; Blomfield, Penelope B; Brand, Alison; Leung, Yee; Oehler, Martin K; Kirk, Judy A; O'Mara, Tracy A; Webb, Penelope M; Spurdle, Amanda B
2017-11-01
To determine endometrial cancer (EC) risk according to family cancer history, including assessment by degree of relatedness, type of and age at cancer diagnosis of relatives. Self-reported family cancer history was available for 1353 EC patients and 628 controls. Logistic regression was used to quantify the association between EC and cancer diagnosis in ≥1 first or second degree relative, and to assess whether level of risk differed by degree of relationship and/or relative's age at diagnosis. Risk was also evaluated for family history of up to three cancers from known familial syndromes (Lynch, Cowden, hereditary breast and ovarian cancer) overall, by histological subtype and, for a subset of 678 patients, by EC tumor mismatch repair (MMR) gene expression. Report of EC in ≥1 first- or second-degree relative was associated with significantly increased risk of EC (P=3.8×10 -7 ), independent of lifestyle risk factors. There was a trend in increasing EC risk with closer relatedness and younger age at EC diagnosis in relatives (P Trend =4.43×10 -6 ), and with increasing numbers of Lynch cancers in relatives (P Trend ≤0.0001). EC risk associated with family history did not differ by proband tumor MMR status, or histological subtype. Reported EC in first- or second-degree relatives remained associated with EC risk after conservative correction for potential misreported family history (OR 2.0; 95% CI, 1.24-3.37, P=0.004). The strongest predictor of EC risk was closer relatedness and younger EC diagnosis age in ≥1 relative. Associations remained significant irrespective of proband MMR status, and after excluding MMR pathogenic variant carriers, indicating that Lynch syndrome genes do not fully explain familial EC risk. Copyright © 2017 Elsevier Inc. All rights reserved.
A multimarker qPCR platform for the characterisation of endometrial cancer.
Supernat, Anna; Łapińska-Szumczyk, Sylwia; Majewska, Hanna; Gulczyński, Jacek; Biernat, Wojciech; Wydra, Dariusz; Zaczek, Anna J
2014-02-01
The molecular background of endometrial cancer (EC) has not been fully elucidated. In the present study, we developed a quantitative PCR (qPCR) platform to examine the gene dosages of the potential molecular markers MGB1, TOP2A, ERBB1-4, MYC, CCND1, ESR1 and PI3K. The platform was applied in samples collected from 157 EC patients (stage I-IV) to verify its clinical utility and to examine the diagnostic and prognostic significance of the analysed biomarkers. The gene dosage pattern of the ERBB family and its downstream effectors PI3K and MYC showed particularly strong correlations with clinicopathological data. The ERBB PI3K/Akt pathway was upregulated in 31 (20%) of 156 cases. Activation of the ERBB PI3K/Akt pathway was positively correlated with a higher stage (p=0.001), higher grade (p=0.001), histological type II disease (p=0.0003) and metastases (p=0.02). The implemented hierarchical clustering revealed that cluster 2 was characterised by high copy numbers of the studied genes. Cluster 2 was associated with shorter overall survival (p=0.05). The platform was found to be a fast and simple method for direct analysis of the genes involved in uterine carcinogenesis, making it feasible for EC biology characterisation.
Sahin, Hilal; Sarioglu, Fatma Ceren; Bagci, Mustafa; Karadeniz, Tugba; Uluer, Hatice; Sanci, Muzaffer
2018-05-01
The aim of this retrospective single-center study was to evaluate the relationship between maximum tumor size, tumor volume, tumor volume ratio (TVR) based on preoperative magnetic resonance (MR) volumetry, and negative histological prognostic parameters (deep myometrial invasion [MI], lymphovascular space invasion, tumor histological grade, and subtype) in International Federation of Gynecology and Obstetrics stage I endometrial cancer. Preoperative pelvic MR imaging studies of 68 women with surgical-pathologic diagnosis of International Federation of Gynecology and Obstetrics stage I endometrial cancer were reviewed for assessment of MR volumetry and qualitative assessment of MI. Volume of the tumor and uterus was measured with manual tracing of each section on sagittal T2-weighted images. Tumor volume ratio was calculated according to the following formula: TVR = (total tumor volume/total uterine volume) × 100. Receiver operating characteristics curve was performed to investigate a threshold for TVR associated with MI. The Mann-Whitney U test, Kruskal-Wallis test, and linear regression analysis were applied to evaluate possible differences between tumor size, tumor volume, TVR, and negative prognostic parameters. Receiver operating characteristics curve analysis of TVR for prediction of deep MI was statistically significant (P = 0.013). An optimal TVR threshold of 7.3% predicted deep myometrial invasion with 85.7% sensitivity, 46.8% specificity, 41.9% positive predictive value, and 88.0% negative predictive value. Receiver operating characteristics curve analyses of TVR, tumor size, and tumor volume for prediction of tumor histological grade or lymphovascular space invasion were not significant. The concordance between radiologic and pathologic assessment for MI was almost excellent (κ value, 0.799; P volumetry, seems to predict deep MI independently in stage I endometrial cancer with insufficient sensitivity and specificity. Its value in clinical practice for
International Nuclear Information System (INIS)
Lee, Kyung Ja
2008-01-01
To evaluate the results and prognostic factors for postoperative adjuvant radiation therapy in patients at stages I and II of endometrial cancer. Materials and Methods: Between January 1991 and December 2006, 35 patients with FIGO stages I and II disease, who received adjuvant radiation therapy following surgery for endometrial cancer at Ewha Womans University Hospital, were enrolled in this study. A total of 17 patients received postoperative pelvic external beam radiation therapy; whereas, 12 patients received vaginal brachytherapy alone, and 6 patients received both pelvic radiation therapy and vaginal brachytherapy. Results: The median follow-up period for all patients was 54 months. The 5-yr overall survival and disease-free survival rates for all patients were 91.4% and 81.7%, respectively. The 5-yr overall survival rates for low-risk, intermediate-risk, and high-risk groups were 100%, 100% and 55.6%, respectively. In addition, the 5-yr disease-free survival rates were 100%, 70.0%, and 45.7%, respectively. Although no locoregional relapses were identified, distant metastases were observed in 5 patients (14%). The most common site of distant metastases was the lung, followed by bone, liver, adrenal gland, and peritoneum. A univariate analysis revealed a significant correlation between distant metastases and risk-group (p=0.018), pathology type (p=0.001), and grade (p=0.019). A multivariate analysis also revealed that distant metastases were correlated with pathology type (p=0.009). Papillary, serous and clear cell carcinoma cases demonstrated a poor patient survival rate compared to cases of endometrioid adenocarcinoma or adenosquamous carcinoma. The most common complication of pelvic external beam radiation therapy was enteritis (30%), followed by proctitis, leucopenia, and lymphedema. All these complications were of RTOG grades 1 and 2; no grades 3 and 4 were observed. Conclusion: For the low-risk and intermediate-risk groups (stages 1 and 2) endometrial
Prognostic factors and treatment of endometrial carcinoma
International Nuclear Information System (INIS)
Aalders, J.G.
1982-01-01
The aim of the present study was to gain more insight into the natural history of endometrial carcinoma, to evaluate prognostic factors and to assess the various treatment methods and the results. Using the data of the Norwegian Radium Hospital, where treatment of gynecological cancer is centralized to a great extent, a large series of patients with long term follow-up, covering all clinical stages and recurrences of endometrial carcinoma, could be evaluated. This resulted in five articles. These articles, together with a study from the University Hospital in Groningen are presented and discussed, and recommendations for treatment are given. The relevant treatments assessed are postoperative external irradiation, preoperative uterine radium packing, preoperative low dose external irradiation and radiotherapy alone. (Auth.)
International Nuclear Information System (INIS)
Schuler, Kevin M; Rambally, Brooke S; DiFurio, Megan J; Sampey, Brante P; Gehrig, Paola A; Makowski, Liza; Bae-Jump, Victoria L
2015-01-01
We conducted a preoperative window study of metformin in endometrial cancer (EC) patients and evaluated its antiproliferative, molecular and metabolic effects. Twenty obese women with endometrioid EC were treated with metformin (850 mg) daily for up to 4 weeks prior to surgical staging. Expression of the proliferation marker Ki-67, estrogen receptor (ER), progesterone receptor (PR), adenosine monophosphate-activated protein kinase (AMPK), and downstream targets of the mammalian target of rapamycin (mTOR) pathway were measured by immunohistochemistry. Global, untargeted metabolomics analysis of serum pre- and postmetformin treatment, and matched tumor, was performed. Metformin reduced proliferation by 11.75% (P = 0.008) based on the comparison of pre- and posttreatment endometrial tumors. A total of 65% of patients responded to metformin as defined by a decrease in Ki-67 staining in their endometrial tumors post-treatment. Metformin decreased expression of phosphorylated (p)-AMPK (P = 0.00001), p-Akt (P = 0.0002), p-S6 (51.2%, P = 0.0002), p-4E-BP-1 (P = 0.001), and ER (P = 0.0002) but not PR expression. Metabolomic profiling of serum indicated that responders versus nonresponders to treatment were more sensitive to metformin's effects on induction of lipolysis, which correlated with increased fatty acid oxidation and glycogen metabolism in matched tumors. In conclusion, metformin reduced tumor proliferation in a pre-operative window study in obese EC patients, with dramatic effects on inhibition of the mTOR pathway. Metformin induced a shift in lipid and glycogen metabolism that was more pronounced in the serum and tumors of responders versus nonresponders to treatment.This study provides support for therapeutic clinical trials of metformin in obese patients with EC
The case against endometrial ablation for treatment of heavy menstrual bleeding.
Louie, Michelle; Wright, Kelly; Siedhoff, Matthew
2018-04-27
Endometrial ablation is a common treatment for heavy menstrual bleeding, but serious limitations and long-term complications exist. Our purpose is to summarize the use of endometrial ablation devices, potential short-term and long-term complications, cost effectiveness, and quality of life in relation to alternative treatments. There is insufficient evidence to strongly recommend one endometrial ablation device over another. Providers should consider and discuss with their patients, complications including risk of future pregnancy, endometrial cancer, and hysterectomy for continued bleeding or pain. Patient selection is key to reducing postablation pain and failure; patients with a history of tubal ligation and dysmenorrhea should consider alternative treatments. All patients should also be counseled that the levonorgestrel intrauterine device is a cost-effective alternative with higher quality of life and fewer complications. Hysterectomy is definitive treatment with higher quality of life and fewer complications. Although endometrial ablation can offer adequate symptom control for patients who have failed medical therapy, desire uterine preservation, or who are high-risk surgical candidates, patients should be appropriately selected and counseled regarding the potential for treatment failure and long-term complications.
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Sudo, Satoko; Sakuragi, Noriaki [Hokkaido University Graduate School of Medicine, Department of Gynecology, Sapporo (Japan); Hattori, Naoya; Manabe, Osamu; Hirata, Kenji; Tamaki, Nagara [Hokkaido University Graduate School of Medicine, Department of Nuclear Medicine, Kitaku, Sapporo (Japan); Kato, Fumi; Mimura, Rie; Magota, Keiichi; Sugimori, Hiroyuki [Hokkaido University Graduate School of Medicine, Department of Diagnostic and Interventional Radiology, Sapporo (Japan)
2015-04-01
The staging of endometrial cancer requires surgery which carries the risk of morbidity. FDG PET/CT combined with anatomical imaging may reduce the number of unnecessary lymphadenectomies by demonstrating the risk of extrapelvic infiltration. The purpose of this study was to optimize FDG PET/CT diagnostic criteria for risk assessment in endometrial cancer after first-line risk triage with MRI. The study population comprised 37 patients who underwent curative surgery for the treatment of endometrial cancer. First, the risk of extrapelvic infiltration was triaged using MRI. Second, multiple glucose metabolic profiles of the primary lesion were assessed with FDG PET/CT, and these were correlated with the histopathological risk of extrapelvic infiltration including lymphovascular space invasion (LVSI) and high-grade malignancy (grades 2 and 3). The results of histological correlation were used to adjust FDG PET/CT diagnostic criteria. Presurgical assessment using MRI was positive for deep (>50 %) myometrial invasion in 17 patients. The optimal FDG PET/CT diagnostic criteria vary depending on the results of MRI. Specifically, SUVmax (≥16.0) was used to indicate LVSI risk with an overall diagnostic accuracy of 88.2 % in patients with MRI findings showing myometrial invasion. High-grade malignancy did not correlate with any of metabolic profiles in this patient group. In the remaining patients without myometrial invasion, lesion glycolysis (LG) or metabolic volume were better indicators of LVSI than SUVmax with the same diagnostic accuracy of 80.0 %. In addition, LG (≥26.9) predicted high-grade malignancy with an accuracy of 72.2 %. Using the optimized cut-off criteria for LVSI, glucose metabolic profiling of primary lesions correctly predicted lymph node metastasis with an accuracy of 73.0 %, which was comparable with the accuracy of visual assessment for lymph node metastasis using MRI and FDG PET/CT. FDG PET/CT diagnostic criteria may need adjustment based on the
Directory of Open Access Journals (Sweden)
Cory A. Rubel
2016-10-01
Full Text Available Altered progesterone responsiveness leads to female infertility and cancer, but underlying mechanisms remain unclear. Mice with uterine-specific ablation of GATA binding protein 2 (Gata2 are infertile, showing failures in embryo implantation, endometrial decidualization, and uninhibited estrogen signaling. Gata2 deficiency results in reduced progesterone receptor (PGR expression and attenuated progesterone signaling, as evidenced by genome-wide expression profiling and chromatin immunoprecipitation. GATA2 not only occupies at and promotes expression of the Pgr gene but also regulates downstream progesterone responsive genes in conjunction with the PGR. Additionally, Gata2 knockout uteri exhibit abnormal luminal epithelia with ectopic TRP63 expressing squamous cells and a cancer-related molecular profile in a progesterone-independent manner. Lastly, we found a conserved GATA2-PGR regulatory network in both human and mice based on gene signature and path analyses using gene expression profiles of human endometrial tissues. In conclusion, uterine Gata2 regulates a key regulatory network of gene expression for progesterone signaling at the early pregnancy stage.
Clinical statistics of gynecologic cancers in Japan
Nagase, Satoru
2017-01-01
Cervical, endometrial, and ovarian cancers, have both high morbidity and mortality among the gynecologic malignant tumors in Japan. The present study was conducted using both the population-based cancer registry and the gynecologic cancer registry to elucidate the characteristics of gynecologic malignant tumors in Japan. Based on nationwide estimates from the population-based cancer registry in Japan, the morbidities and mortality of cervical, endometrial, and ovarian cancers were obtained and used for analysis. Clinicopathologic factors for cervical cancer, endometrial cancer, ovarian cancer, including age, clinical stage, postsurgical stage, histological type, therapeutic strategy, and prognosis were retrieved from the gynecologic cancer registry published by the Japan Society of Obstetrics and Gynecology and used for analysis. The morbidities of cervical, endometrial, and ovarian cancers were 10,908, 13,606, and 9,384 women in 2012, respectively. The prevalence of endometrial cancer has significantly and consistently been increasing and represents the most common gynecologic malignant tumor in Japan. The mortalities of cervical, endometrial, and ovarian cancers were 2.1, 1.3, and 3.2 per 100,000 in 2012, respectively. In 2014, 52.2% of cervical cancer patients were classified as stage I, 22.5% as stage II, 10.2% as stage III, and 11.2% as stage IV. In addition, 71.9% of endometrial cancer patients were classified as stage I, 6.0% as stage II, 13.3% as stage III, and 7.5% as stage IV. Finally, 43.2% of ovarian cancer patients were classified as stage I, 9.1% as stage II, 27.6% as stage III, and 7.2% as stage IV. Twelve-point six percent of ovarian cancer patients received neoadjuvant chemotherapy. PMID:28198168
Atiomo, William; Shafiee, Mohamad Nasir; Chapman, Caroline; Metzler, Veronika M; Abouzeid, Jad; Latif, Ayşe; Chadwick, Amy; Kitson, Sarah; Sivalingam, Vanitha N; Stratford, Ian J; Rutland, Catrin S; Persson, Jenny L; Ødum, Niels; Fuentes-Utrilla, Pablo; Jeyapalan, Jennie N; Heery, David M; Crosbie, Emma J; Mongan, Nigel P
2017-11-01
Women with a prior history of polycystic ovary syndrome (PCOS) have an increased risk of endometrial cancer (EC). To investigate whether the endometrium of women with PCOS possesses gene expression changes similar to those found in EC. Patients with EC, PCOS and control women unaffected by either PCOS or EC were recruited into a cross-sectional study at the Nottingham University Hospital, UK. For RNA sequencing, representative individual endometrial biopsies were obtained from women with EC, PCOS and a woman unaffected by PCOS or EC. Expression of a subset of differentially expressed genes identified by RNA sequencing, including NAD(P)H quinone dehydrogenase 1 (NQO1), was validated by quantitative reverse transcriptase PCR validation (n = 76) and in the cancer genome atlas UCEC (uterine corpus endometrioid carcinoma) RNA sequencing data set (n = 381). The expression of NQO1 was validated by immunohistochemistry in EC samples from a separate cohort (n = 91) comprised of consecutive patients who underwent hysterectomy at St Mary's Hospital, Manchester, between 2011 and 2013. A further 6 postmenopausal women with histologically normal endometrium who underwent hysterectomy for genital prolapse were also included. Informed consent and local ethics approval were obtained for the study. We show for the first that NQO1 expression is significantly increased in the endometrium of women with PCOS and EC. Immunohistochemistry confirms significantly increased NQO1 protein expression in EC relative to nonmalignant endometrial tissue (P < .0001). The results obtained here support a previously unrecognized molecular link between PCOS and EC involving NQO1. © 2017 The Authors. Clinical Endocrinology Published by John Wiley & Sons Ltd.
Association of Ulex europaeus agglutinin I binding with invasion in endometrial carcinoma.
Ambros, R A; Kurman, R J
1993-10-01
Ulex europaeus agglutinin I (UEA-I), a lectin which specifically binds L-fucose, has been shown to extensively bind endometrial carcinoma cells but not benign endometrial glands. Patterns of UEA-I binding were examined in five cases of uteri containing proliferative endometrium, five cases of endometrial hyperplasia, and 54 cases of endometrioid (typical) carcinoma of the endometrium and correlated with the histologic features of the tumor and its behavior. Whereas proliferative endometrium showed luminal staining only, diffuse cytoplasmic staining was frequently seen in hyperplasia and carcinoma. Carcinomas with a high percentage of tumor cells staining with UEA-I tended to be high-grade with a greater tendency to deep myometrial and vascular invasion than tumors with little or no staining. By univariate survival analysis, the extent of UEA-I binding was found to correlate with patient survival. By multivariate analysis, however, survival correlated most closely with the presence of deep myometrial and vascular invasion, and UEA-I binding was not found to be an independent prognostic indicator. This study suggests that increased fucosylation of proteins in endometrioid cancer cells may play a role in myometrial and vascular invasion.
Kunneman, M; Pieterse, A H; Stiggelbout, A M; Nout, R A; Kamps, M; Lutgens, L C H W; Paulissen, J; Mattheussens, O J A; Kruitwagen, R F P M; Creutzberg, C L
2014-08-12
Vaginal brachytherapy (VBT) in high-intermediate-risk endometrial cancer (EC) provides a significant reduction in the risk of local cancer recurrence, but without survival benefit and with increased mucosal atrophy. Five-year local control is estimated to be similar for VBT and a watchful waiting policy (WWP), in which patients receive VBT combined with external radiation in case of a recurrence. Our aim was to assess treatment preferences of EC patients and clinicians regarding VBT and WWP, and to evaluate their preferred and perceived involvement in treatment decision making. Interviews were held with 95 treated EC patients. The treatment trade-off method was used to assess the minimally desired benefit from VBT in local control. Patients' preferred and perceived involvement in decision making were assessed using a questionnaire. Seventy-seven clinicians completed a questionnaire assessing their minimally desired benefit and preferred involvement in decision making. Minimally desired benefit of VBT was significantly lower for patients than for clinicians (median=0 vs 8%, Pdecision about VBT. However, irradiated patients indicated low perceived involvement in actual treatment decision making. We found variations between and within patients and clinicians in minimally desired benefit from VBT. However, the recurrence risk at which patients preferred VBT was low. Our results showed that patients consider active participation in decision making essential.
Isolated splenic metastasis of endometrial adenocarcinoma--a case report.
Andrei, S; Preda, C; Andrei, A; Becheanu, G; Herlea, V; Lupescu, I; Popescu, I
2011-01-01
The spleen in rarely the place for solid, non-haematological tumors, isolated splenic metastases from adenocarcinomas being extremely rare findings, regardless of the origin and the histological type of the primary tumor. We present the case of a female patient with isolated splenic metastasis diagnosed by abdominal computer tomography at only 20 months after curative surgery for endometrial adenocarcinoma, in which the final diagnosis has been established by histological and immunohistochemical examination of the splenectomy piece. The haematogenous dissemination of the endometrial cancer occurs most commonly in the lungs, liver or bones, the spleen being rarely affected. In the medical literature there are cited up to date only 12 cases of solitary splenic metastasis from endometrial adenocarcinoma. The particularity of the case presented by us is the early appearance of an isolated splenic metastasis, at less than two years after curative surgery (compared to an average of 4-5 years cited in the literature), from an endometrial cancer which was classified histologicaly in the group with low-risk for relapse (well differentiated endometrioid adenocarcinoma). In conclusion, although solitary splenic secondary determinations are very rare, the incidence of the reported cases in the medical literature is increasing, their late appearance (a few years after the primary tumor's resection) and the lack of symptoms until the tumor reaches appreciable size or it complicates with necrosis, justifies the periodic abdominal imaging examination, on long-term, for postoperative monitorisation after the initial curative surgery. Their treatment of choice is open, classical splenectomy that must be followed by chemotherapy in order to prevent the development of other possible micrometastases.
Myriokefalitaki, Eva; Vorgias, George; Vlahos, George; Rodolakis, Alexandros
2015-09-01
To evaluate preoperative serum levels of Ca125 and Tag72-4 tumour markers and investigate if abnormal levels correlate to mortality and disease-free survival. Retrospective observational study of a cohort of 282 women (mean age 62.3, SD 10.5 years) with primary endometrial cancer included all consecutive cases treated in a tertiary Gynaecological oncology Center. Excluded cases with other cancer or previous cancer treatment, major abdominal pathology or inflammation, endometriosis. Preoperative serum Tag72 and Ca125 levels were determined and evaluated in relation to disease-free survival (DFS) and disease-specific overall survival (DOS). Raised Ca125 correlates to worse overall disease-specific survival (66.1 vs 87.8 months, p = 0.021) and Tag72 correlates to shorter disease-free survival (69.2 vs 67.3 months, p = 0.021) and higher recurrence rate (13.5 vs 6 %, p = 0.021). When both Ca125 and Tag72 are abnormal DFS and DOS are worse. 93.3 % (72.3 months) vs 82.4 %, (61.3 months) p = 0.018 and 96.3 % (74.8 months) vs 88.2 %, (65.9 months) p = 0.021, respectively. This study enhances the value of preoperative tumour markers and their prognostic value. Ca125 and Tag72 appear to be good predictors of poor prognosis in patients with endometrial cancer.
The Relationship Between Body Mass Index and Sexual Function in Endometrial Cancer .
Garcia, Rubi M; Hanlon, Alexandra; Small, William; Strauss, Jonathan B; Lin, Lillie; Wells, Jessica; Bruner, Deborah W
2018-01-01
To explore the association between pretreatment body mass index (BMI) and post-treatment sexual function in women treated for endometrial cancer. . 28 postmenopausal women treated with vaginal brachytherapy (VBT) took part in this multisite exploratory secondary analysis at the University of Pennsylvania and Northwestern University. . Secondary data analysis was used to determine if pretreatment BMI is associated with post-VBT sexual function in postmenopausal women treated for endometrial cancer at baseline and at six months post-treatment. Because of small sample size, participants were dichotomized according to enrollment BMI. Both groups had poor sexual function at baseline. Although improved function was observed with time, neither group reached a score indicating healthy sexual function. . Understanding factors that influence sexual health in patients with gynecologic cancer can improve post-treatment quality of life. .
Zhao, Li-Ting; Xiang, Yu-Hong; Dai, Yin-Mei; Zhang, Zhuo-Yong
2010-04-01
Near infrared spectroscopy was applied to measure the tissue slice of endometrial tissues for collecting the spectra. A total of 154 spectra were obtained from 154 samples. The number of normal, hyperplasia, and malignant samples was 36, 60, and 58, respectively. Original near infrared spectra are composed of many variables, for example, interference information including instrument errors and physical effects such as particle size and light scatter. In order to reduce these influences, original spectra data should be performed with different spectral preprocessing methods to compress variables and extract useful information. So the methods of spectral preprocessing and wavelength selection have played an important role in near infrared spectroscopy technique. In the present paper the raw spectra were processed using various preprocessing methods including first derivative, multiplication scatter correction, Savitzky-Golay first derivative algorithm, standard normal variate, smoothing, and moving-window median. Standard deviation was used to select the optimal spectral region of 4 000-6 000 cm(-1). Then principal component analysis was used for classification. Principal component analysis results showed that three types of samples could be discriminated completely and the accuracy almost achieved 100%. This study demonstrated that near infrared spectroscopy technology and chemometrics method could be a fast, efficient, and novel means to diagnose cancer. The proposed methods would be a promising and significant diagnosis technique of early stage cancer.
Breast and gynecological cancers in Croatia, 1988-2008
Kelava, Iva; Tomičić, Karlo; Kokić, Marina; Ćorušić, Ante; Planinić, Pavao; Kirac, Iva; Murgić, Jure; Kuliš, Tomislav; Znaor, Ariana
2012-01-01
Aim To analyze and interpret incidence and mortality trends of breast and ovarian cancers and incidence trends of cervical and endometrial cancers in Croatia for the period 1988-2008. Methods Incidence data were obtained from the Croatian National Cancer Registry. The mortality data were obtained from the World Health Organization (WHO) mortality database. Trends of incidence and mortality were analyzed by joinpoint regression analysis. Results Joinpoint analysis showed an increase in the incidence of breast cancer with estimated annual percent of change (EAPC) of 2.6% (95% confidence interval [CI], 1.9 to 3.4). The mortality rate was stable, with the EAPC of 0.3% (95% CI, -0.6 to 0.0). Endometrial cancer showed an increasing incidence trend, with EAPC of 0.8% (95% CI, 0.2 to 1.4), while cervical cancer showed a decreasing incidence trend, with EAPC of -1.0 (95% CI, -1.6 to -0.4). Ovarian cancer incidence showed three trends, but the average annual percent change (AAPC) for the overall period was not significant, with a stable trend of 0.1%. Ovarian cancer mortality was increasing since 1992, with EAPC of 1.2% (95% CI, 0.4 to 1.9), while the trend for overall period was stable with AAPC 0.1%. Conclusion Incidence trends of breast, endometrial, and ovarian cancers in Croatia 1988-2008 are similar to the trends observed in most of the European countries, while the modest decline in cervical cancer incidence and lack of decline in breast cancer mortality suggest suboptimal cancer prevention and control. PMID:22522987
Self-Advocacy Serious Game in Advanced Cancer
2018-04-05
Ovarian Cancer Stage III; Ovarian Cancer Stage IV; Breast Cancer Stage IV; Cervical Cancer Stage IIIB; Cervical Cancer Stage IVA; Cervical Cancer Stage IVB; Endometrial Cancer Stage III; Endometrial Cancer Stage IV; Vulvar Cancer, Stage III; Vulvar Cancer, Stage IV; Vaginal Cancer Stage III; Vaginal Cancer Stage IVA; Vaginal Cancer Stage IVB
dos Santos Silva, I.; Swerdlow, A. J.
1995-01-01
Reproductive-related factors play a major role in the aetiology of cancers of the breast, ovary and endometrium. Pregnancy history influences the risk of each of these cancers, and oral contraceptive use modifies the risks of ovarian and endometrial cancers, although its effect on breast cancer risk is less certain. We analysed recent time trends in the incidence and mortality of these cancers in England and Wales and assessed whether they can be explained by changes in fertility and oral con...
Kyrgiou, Maria; Swart, Anne-Marie; Qian, Wendi; Warwick, Jane
2015-10-01
Laparoscopic hysterectomy (LH) is increasingly used for the management of endometrial malignancy. Its benefits may be particularly pronounced as these women are more likely to be older or obese. The aim of this study was to determine whether outcomes for LH are comparable to the open hysterectomy (OH). This was a prospective cohort study nested within the multicenter ASTEC (A Study in the Treatment of Endometrial Cancer) randomized controlled trial (1998-2005). Women with presumed early endometrial cancer were included. Laparoscopic hysterectomy was compared with OH with or without systematic lymphadenectomy. Overall survival, time to first recurrence, complication rates, and surgical outcomes were the main outcome measures. Of 1408 women, 1309 (93%) received OH, and 99 (7%) had LH. LH was associated with longer operating time (median, LH 105 minutes [interquartile range (IQR), 60-150] vs OH 80 minutes [IQR, 60-95]; P < 0.001) but 50% shorter hospital stay (median, LH 4 days [IQR, 3-5] vs OH 6 days [IQR, 5-7]). The number of harvested lymph nodes was similar (median, LH 13 [IQR, 10-16] vs OH 12 [IQR, 11-13]; P = 0.67). LH had fewer intraoperative and postoperative adverse events (9% difference, LH 21% vs OH 30%; borderline significance; P = 0.07). The rate of conversion to laparotomy for the LH group was high (27%). The median follow-up was 37 months. After adjusting for significant prognostic factors, the hazard ratio for overall survival in those who underwent LH compared with those who underwent OH was 0.67 (95% confidence interval, 0.31-1.43) (P = 0.30). Laparoscopic hysterectomy for early endometrial cancer is safe. Although it requires longer operating time it is associated with shorter hospital stay and favorable morbidity profile. Further studies are required to assess the long-term safety.
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Małgorzata Moszyńska-Zielińska
2014-05-01
Full Text Available The increasing incidence of obesity in Poland and its relation to endometrioid endometrial cancer (EEC is resulting in the increasing necessity of treating obese women. Treatment of an overweight patient with EEC may impede not only the surgical procedures but also radiotherapy, especially external beam radiotherapy (EBRT. The problems arise both during treatment planning and when delivering each fraction due to the difficulty of positioning such a patient – it implies the danger of underdosing targets and overdosing organs at risk. Willingness to use dynamic techniques in radiation oncology has increased for patients with EEC, even those who are obese. During EBRT careful daily verification is necessary for both safety and treatment accuracy. The most accurate method of verification is cone beam computed tomography (CBCT with soft tissue assessment, although it is time consuming and often requires a radiation oncologist. In order to improve the quality of such treatment, the authors present the practical aspects of planning and treatment itself by means of dynamic techniques in EBRT. The authors indicate the advantages and disadvantages of different types of on-board imaging (OBI verification images. Considering the scanty amount of literature in this field, it is necessary to conduct further research in order to highlight proper planning and treatment of obese endometrial cancer patients. The review of the literature shows that all centres that wish to use EBRT for gynaecological tumours should develop their own protocols on qualification, planning the treatment and methods of verifying the patients’ positioning.
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Masroor, I.; Hussain, Z.; Taufiq, M.
2016-01-01
Objective: To determine the diagnostic accuracy of Diffusion-Weighted Magnetic Resonance Imaging (DWMRI) in the detection of myometrial invasion in endometrial cancer taking histopathology as gold standard. Study Design: Cross-sectional validation study. Place and Duration of Study: Department of Radiology, The Aga Khan University Hospital, Karachi, from January to December 2012. Methodology: DWMRI (b-value = 50,400 and 800 s/mm2) was performed in 85 patients of biopsy-proven endometrial carcinoma before hysterectomy using body and spine coil at 1.5 Tesla. DWI was evaluated for presence of myometrial invasion by tumor with histopathology as gold standard. Sensitivity, specificity, the negative predictive value and positive predictive value and accuracy of DWI were assessed against the gold standard. Results: On DWI, superficial myometrial invasion was found in 42 patients and deep myometrial invasion in 43. On histopathology, superficial myometrial invasion was found in 53 patients and deep myometrial invasion in 32. Hence sensitivity, specificity, positive predictive value, negative predictive value and accuracy for the assessment of myometrial invasion by endometrial tumor on DW images was 90 percentage, 73 percentage, 67 percentage, 92 percentage and 80 percentage, respectively. Diagnostic accuracy of diffusion-weighted magnetic resonance imaging in detection of myometrial invasion in endometrial cancer was 80 percentage. Conclusion: DWI is highly accurate in assessing myometrial invasion and can be used as an adjunct to routine MRI for pre-operative evaluation of myometrial invasion of endometrial cancer. (author)
Endometrial carcinoma occuring from polycystic ovary disease : A case report
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Seong, Su Ok; Jeon, Woo Ki
1996-01-01
Endometrial carcinoma usually occurs in postmenopausal women ; less than 5% occurs in women under the age of 40. Up to one quarter of endometrial carcinoma patients below this age have PCO(polycystic ovary disease, Stein-Leventhal syndrome). The increased incidence of endometrial carcinoma in patients with PCO is related to chronic estrogenic stimulation. We report MR imaging in one case of endometrial carcinoma occuring in a 23 year old woman with PCO and had complained of hypermenorrhea for about three years. On T2-weighted MR image the endometrial cavity was seen to be distended with protruded endometrial masses of intermediate signal intensity, and the junctional zone was disrupted beneath the masses. Both ovaries were best seen on T2-weighted MR imaging and showed multiple small peripheral cysts and low signal-intensity central stroma
Endometrial carcinoma occuring from polycystic ovary disease : A case report
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Seong, Su Ok; Jeon, Woo Ki [Inje Univ. College of Medicine, Seoul (Korea, Republic of)
1996-12-01
Endometrial carcinoma usually occurs in postmenopausal women ; less than 5% occurs in women under the age of 40. Up to one quarter of endometrial carcinoma patients below this age have PCO(polycystic ovary disease, Stein-Leventhal syndrome). The increased incidence of endometrial carcinoma in patients with PCO is related to chronic estrogenic stimulation. We report MR imaging in one case of endometrial carcinoma occuring in a 23 year old woman with PCO and had complained of hypermenorrhea for about three years. On T2-weighted MR image the endometrial cavity was seen to be distended with protruded endometrial masses of intermediate signal intensity, and the junctional zone was disrupted beneath the masses. Both ovaries were best seen on T2-weighted MR imaging and showed multiple small peripheral cysts and low signal-intensity central stroma.
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Creutzberg, Carien L., E-mail: c.l.creutzberg@lumc.nl [Department of Clinical Oncology, Leiden University Medical Center, Leiden (Netherlands); Stiphout, Ruud G.P.M. van [Department of Radiation Oncology, MAASTRO, GROW, University Medical Centre Maastricht, Maastricht (Netherlands); Nout, Remi A. [Department of Clinical Oncology, Leiden University Medical Center, Leiden (Netherlands); Lutgens, Ludy C.H.W. [Department of Radiation Oncology, MAASTRO, GROW, University Medical Centre Maastricht, Maastricht (Netherlands); Jürgenliemk-Schulz, Ina M. [Department of Radiation Oncology, University Medical Center Utrecht, Utrecht (Netherlands); Jobsen, Jan J. [Department of Radiotherapy, Medisch Spectrum Twente, Enschede (Netherlands); Smit, Vincent T.H.B.M. [Department of Pathology, Leiden University Medical Center, Leiden (Netherlands); Lambin, Philippe [Department of Radiation Oncology, MAASTRO, GROW, University Medical Centre Maastricht, Maastricht (Netherlands)
2015-03-01
Background: Postoperative radiation therapy for stage I endometrial cancer improves locoregional control but is without survival benefit. To facilitate treatment decision support for individual patients, accurate statistical models to predict locoregional relapse (LRR), distant relapse (DR), overall survival (OS), and disease-free survival (DFS) are required. Methods and Materials: Clinical trial data from the randomized Post Operative Radiation Therapy for Endometrial Cancer (PORTEC-1; N=714 patients) and PORTEC-2 (N=427 patients) trials and registered group (grade 3 and deep invasion, n=99) were pooled for analysis (N=1240). For most patients (86%) pathology review data were available; otherwise original pathology data were used. Trial variables which were clinically relevant and eligible according to data constraints were age, stage, given treatment (pelvic external beam radiation therapy (EBRT), vaginal brachytherapy (VBT), or no adjuvant treatment, FIGO histological grade, depth of invasion, and lymph-vascular invasion (LVSI). Multivariate analyses were based on Cox proportional hazards regression model. Predictors were selected based on a backward elimination scheme. Model results were expressed by the c-index (0.5-1.0; random to perfect prediction). Two validation sets (n=244 and 291 patients) were used. Results: Accuracy of the developed models was good, with training accuracies between 0.71 and 0.78. The nomograms validated well for DR (0.73), DFS (0.69), and OS (0.70), but validation was only fair for LRR (0.59). Ranking of variables as to their predictive power showed that age, tumor grade, and LVSI were highly predictive for all outcomes, and given treatment for LRR and DFS. The nomograms were able to significantly distinguish low- from high-probability patients for these outcomes. Conclusions: The nomograms are internally validated and able to accurately predict long-term outcome for endometrial cancer patients with observation, pelvic EBRT, or VBT
Sonohysterographic findings of endometrial abnormalities in women with polycystic ovarian disease
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Lee, Eun Ju [Ajou University School of Medicine, Suwon (Korea, Republic of)
2004-06-15
To describe the sonohysterographic findings of endometrial abnormalities, and to determine the usefulness of sonohysterography (SH) for predicting endometrial abnormalities in women with polycystic ovarian disease(PCOD). 82 patients with PCOD who had vaginal bleeding or endometrial thickening and lesion mass on baseline transvaginal sonography were prospectively examined with SH. The SH findings were evaluated for endometrial thickness, the presence of endometrial thickening and lesion mass, echogenicity and surface contour, distensibility of the endometrial cavity, and disruption of endometrial-myometrial interface. These findings were compared with the pathologic findings and the diagnostic accuracy of SH for predicting endometrial abnormalities was assessed. Endometrial abnormalities were identified in 47 (57.3%) of 82 PCOD patients, and their pathologic diagnosis included endometrial carcinoma in 7 cases, hyperplasia in 19 cases (atypical hyperplasia, n=5), and polyp in 21 cases. Of the 35 patients who did not have endometrial abnormalities, there was disordered proliferative endometrium in 18 cases and normal proliferative or secretory endometrium in 17 cases. The SH findings of endometrial carcinoma were endometrial thickening in 5 cases, endometrial thickening and lesion mass in 2 cases, and the endometrial thickness ranged from 6 mm to 15 mm (mean 9.5 mm). They were characterized as a diffuse polyploid endometrial thickening or a sessile endometrial mass with irregular surface, homogeneous hyperechogenicity, and obliteration of the endometrial cavity. Endometrial hyperplasia appeared as endometrial thickening in 14 cases, endometrial lesion mass in 3 cases, and endometrial thickening and lesion mass in 2 cases, and the endometrial thickness was between 6.5-10.7 mm (mean 8.2 mm). They showed a diffuse uniform endometrial thickening or a polyploid endometrial lesion mass with homogeneous hyperechogenicity and a regular surface. Endometrial polyps appeared as
Sonohysterographic findings of endometrial abnormalities in women with polycystic ovarian disease
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Lee, Eun Ju
2004-01-01
To describe the sonohysterographic findings of endometrial abnormalities, and to determine the usefulness of sonohysterography (SH) for predicting endometrial abnormalities in women with polycystic ovarian disease(PCOD). 82 patients with PCOD who had vaginal bleeding or endometrial thickening and lesion mass on baseline transvaginal sonography were prospectively examined with SH. The SH findings were evaluated for endometrial thickness, the presence of endometrial thickening and lesion mass, echogenicity and surface contour, distensibility of the endometrial cavity, and disruption of endometrial-myometrial interface. These findings were compared with the pathologic findings and the diagnostic accuracy of SH for predicting endometrial abnormalities was assessed. Endometrial abnormalities were identified in 47 (57.3%) of 82 PCOD patients, and their pathologic diagnosis included endometrial carcinoma in 7 cases, hyperplasia in 19 cases (atypical hyperplasia, n=5), and polyp in 21 cases. Of the 35 patients who did not have endometrial abnormalities, there was disordered proliferative endometrium in 18 cases and normal proliferative or secretory endometrium in 17 cases. The SH findings of endometrial carcinoma were endometrial thickening in 5 cases, endometrial thickening and lesion mass in 2 cases, and the endometrial thickness ranged from 6 mm to 15 mm (mean 9.5 mm). They were characterized as a diffuse polyploid endometrial thickening or a sessile endometrial mass with irregular surface, homogeneous hyperechogenicity, and obliteration of the endometrial cavity. Endometrial hyperplasia appeared as endometrial thickening in 14 cases, endometrial lesion mass in 3 cases, and endometrial thickening and lesion mass in 2 cases, and the endometrial thickness was between 6.5-10.7 mm (mean 8.2 mm). They showed a diffuse uniform endometrial thickening or a polyploid endometrial lesion mass with homogeneous hyperechogenicity and a regular surface. Endometrial polyps appeared as
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Shi-Wen Jiang
2013-11-01
Full Text Available We investigated the HE4 variant-specific expression patterns in various normal tissues as well as in normal and malignant endometrial tissues. The relationships between mRNA variants and age, body weight, or survival are analyzed. ICAT-labeled normal and endometrial cancer (EC tissues were analyzed with multidimensional liquid chromatography followed by tandem mass spectrometry. Levels of HE4 mRNA variants were measured by real-time PCR. Mean mRNA levels were compared among 16 normal endometrial samples, 14 grade 1 and 14 grade 3 endometrioid EC, 15 papillary serous EC, and 14 normal human tissue samples. The relationship between levels of HE4 variants and EC patient characteristics was analyzed with the use of Pearson correlation test. We found that, although all five HE4 mRNA variants are detectable in normal tissue samples, their expression is highly tissue-specific, with epididymis, trachea, breast and endometrium containing the highest levels. HE4-V0, -V1, and -V3 are the most abundant variants in both normal and malignant tissues. All variants are significantly increased in both endometrioid and papillary serous EC, with higher levels observed in grade 3 endometrioid EC. In the EC group, HE4-V1, -V3, and -V4 levels inversely correlate with EC patient survival, whereas HE4-V0 levels positively correlate with age. HE4 variants exhibit tissue-specific expression, suggesting that each variant may exert distinct functions in normal and malignant cells. HE4 levels appear to correlate with EC patient survival in a variant-specific manner. When using HE4 as a biomarker for EC management, the effects of age should be considered.
de Boer, Stephanie M.; Powell, Melanie E.; Mileshkin, Linda; Katsaros, Dionyssios; Bessette, Paul; Haie-Meder, Christine; Ottevanger, Petronella B.; Ledermann, Jonathan A.; Khaw, Pearly; Colombo, Alessandro; Fyles, Anthony; Baron, Marie-Helene; Jurgenliemk-Schulz, Ina M.; Kitchener, Henry C.; Nijman, Hans W.; Wilson, Godfrey; Brooks, Susan; Carinelli, Silvestro; Provencher, Diane; Hanzen, Chantal; Lutgens, Ludy C. H. W.; Smit, Vincent T. H. B. M.; Singh, Naveena; Do, Viet; D'Amico, Romerai; Nout, Remi A.; Feeney, Amanda; Verhoeven-Adema, Karen W.; Putter, Hein; Creutzberg, Carien L.
Background Although women with endometrial cancer generally have a favourable prognosis, those with high-risk disease features are at increased risk of recurrence. The PORTEC-3 trial was initiated to investigate the benefit of adjuvant chemotherapy during and after radiotherapy (chemoradiotherapy)
de Boer, Stephanie M.; Powell, Melanie E.; Mileshkin, Linda; Katsaros, Dionyssios; Bessette, Paul; Haie-Meder, Christine; Ottevanger, Petronella B.; Ledermann, Jonathan A.; Khaw, Pearly; Colombo, Alessandro; Fyles, Anthony; Baron, Marie Helene; Jürgenliemk-Schulz, Ina M.; Kitchener, Henry C.; Nijman, Hans W.; Wilson, Godfrey; Brooks, Susan; Carinelli, Silvestro; Provencher, Diane; Hanzen, Chantal; Lutgens, Ludy C.H.W.; Smit, Vincent T.H.B.M.; Singh, Naveena; Do, Viet; D'Amico, Romerai; Nout, Remi A.; Feeney, Amanda; Verhoeven-Adema, Karen W.; Putter, Hein; Creutzberg, Carien L.; McCormack, Mary; Whitmarsh, Karen; Allerton, Rozenn; Gregory, Deborah; Symonds, Paul; Hoskin, Peter J.; Adusumalli, Madhavi; Anand, Anjana; Wade, Robert; Stewart, Alexandra; Taylor, Wendy; Kruitwagen, Roy F.P.M.; Hollema, Harry; Pras, Elizabeth; Snyers, An; Stalpers, Lukas; Jobsen, Jan J.; Slot, Annerie; Mens, Jan Willem M.; Stam, Tanja C.; Van Triest, Baukelien; Van der Steen - Banasik, Elzbieta M.; De Winter, Karin A.J.; Quinn, Michael A.; Kolodziej, Ilka; Pyman, Jan; Johnson, Carol; Capp, Anne; Fossati, Roldano; Gribaudo, Sergio; Lissoni, Andrea A.; Ferrero, Annamaria; Artioli, Grazia; Davidson, Cathy; McLachlin, C. Meg; Ghatage, Prafull; Rittenberg, Paula V.C.; Souhami, Luis; Thomas, Gillian; Duvillard, Pierre; Berton-Rigaud, Dominique; Tubiana-Mathieu, Nicole
2018-01-01
Background: Although women with endometrial cancer generally have a favourable prognosis, those with high-risk disease features are at increased risk of recurrence. The PORTEC-3 trial was initiated to investigate the benefit of adjuvant chemotherapy during and after radiotherapy (chemoradiotherapy)
A CLINICAL STUDY OF ENDOMETRIAL HISTOPATHOLOGY IN AUB AND INCIDENCE OF ENDOMETRIAL POLYP IN AUB
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Renuka Devi Balakrishnan
2016-11-01
Full Text Available BACKGROUND Abnormal Uterine Bleeding (AUB is one of the most common menstrual complaints and a frequent indication for hysterectomy. It can be a manifestation of any number of pathological entities. Causes of AUB ranges from organic pathologies like leiomyoma, polyps, adenomyosis and malignancy to conditions like coagulopathy and drug-induced AUB and aetiologies vary in different age groups. Histopathological evaluation of endometrium is very vital to identify the cause of AUB. The objectives of this study are to, 1. To evaluate the endometrial histopathology in AUB, and 2. To estimate the incidence of endometrial polyp in AUB. MATERIALS AND METHODS This is a prospective study carried out on 120 women who presented with AUB. Endometrial samples collected were analysed for their histopathological pattern. RESULTS Out of 120 endometrial samples analysed among women of 30-39 years, proliferative endometrium was seen in 43.3% and secretory endometrium in 33.3% and endometrial polyp in 13.3%. In women of 40-49 years, proliferative endometrium in 36.8%, secretory endometrium in 30.9% and disordered proliferative endometrium was seen in 19% of women. The incidence of endometrial polyp was found to be 8.3% in our study. CONCLUSION There is an age-specific relation of abnormal endometrial histopathology. Among abnormal endometrial pathology, disordered proliferative endometrium was more common in perimenopausal age group and endometrial polyps in reproductive age group. The results of this study indicate that benign endometrial histopathology is common in AUB suggesting a role for more conservative therapeutic strategies.
Li, Yinghua; Xie, Yunpeng; Cui, Dan; Ma, Yanni; Sui, Linlin; Zhu, Chenyang; Kong, Hui; Kong, Ying
2015-01-01
Osteopontin (OPN) is an Extracellular Matrix (ECM) molecule and is involved in many physiologic and pathologic processes, including cell adhesion, angiogenesis and tumor metastasis. OPN is a well-known multifunctional factor involved in various aspects of cancer progression, including endometrial cancer. In this study, we examined the significance of OPN in endometrial cancer. The proliferation, migration and invasion ability of HEC-1A cells were detected by Cell Counting Kit-8 (CCK-8), Wound scratch assay and transwell. Western blots were employed to detect the expression of Matrix metalloproteinase-2 (MMP-2) and epithelial-mesenchymal transition (EMT)-related factors in HEC-1A cells treated with rhOPN. rhOPN promotes cell proliferation, migration and invasion in HEC-1A cells. rhOPN influenced EMT-related factors and MMP-2 expression in HEC-1A cells. rhOPN promoted HEC-1A cells migration, invasion and EMT through protein kinase B (PKB/AKT) and Extracellular regulated protein kinases (ERK1/2) signaling pathway. These results may open up a novel therapeutic strategy for endometrial cancer: namely, rhOPN have important roles in controlling growth of endometrial of cancer cells and suggest a novel target pathway for treatment of this cancer. © 2015 The Author(s) Published by S. Karger AG, Basel.
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Yinghua Li
2015-10-01
Full Text Available Background/Aims: Osteopontin (OPN is an Extracellular Matrix (ECM molecule and is involved in many physiologic and pathologic processes, including cell adhesion, angiogenesis and tumor metastasis. OPN is a well-known multifunctional factor involved in various aspects of cancer progression, including endometrial cancer. In this study, we examined the significance of OPN in endometrial cancer. Methods: The proliferation, migration and invasion ability of HEC-1A cells were detected by Cell Counting Kit-8 (CCK-8, Wound scratch assay and transwell. Western blots were employed to detect the expression of Matrix metalloproteinase-2 (MMP-2 and epithelial-mesenchymal transition (EMT-related factors in HEC-1A cells treated with rhOPN. Results: rhOPN promotes cell proliferation, migration and invasion in HEC-1A cells. rhOPN influenced EMT-related factors and MMP-2 expression in HEC-1A cells. rhOPN promoted HEC-1A cells migration, invasion and EMT through protein kinase B (PKB/AKT and Extracellular regulated protein kinases (ERK1/2 signaling pathway. Conclusions: These results may open up a novel therapeutic strategy for endometrial cancer: namely, rhOPN have important roles in controlling growth of endometrial of cancer cells and suggest a novel target pathway for treatment of this cancer.
Endometrial adenocarcinoma recurrence presenting with tibial metastasis: Report of a case
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Mehmet Salih Söylemez
2017-01-01
Conclusion: Recurrence of endometrial cancer as a solitary bone lesion is a rare situation. Wide resection and reconstruction with an allograft or an intercalar prosthesis might be an option to increase survival and possible cure of the patient.
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Strecker, Ernst-Peter; Heber, Ralf; Boos, Irene; Goettmann, Dieter; Heinrich, Dirk
2003-01-01
The purpose of this study was to assess the suitability of a percutaneously implantable catheter port system (PIPS)for repeated intraarterial locoregional chemotherapy (ILC) for cervical and endometrial carcinoma. In 30 patients with advanced, recurrent, or high-risk cervical (n 23) or endometrial(n = 7) carcinoma, PIPS for ILC was implanted via a femoral access, the catheter localized in the infrarenal abdominal aorta. Chemotherapy was performed adjuvantly after surgery(n = 14) or neo-adjuvantly to enable surgery, or for palliation (n = 16). Port implantation, catheter placement, and repeated port puncture was uneventful in all patients.Complications included catheter dislocation (n = 1),catheter thrombosis (n = 2), subcutaneous infection(n = 1), port-bed skin atrophy (n = 1),requiring port explantation in 3 patients. At 2 years follow-up,complete remission was observed in 7/14 patients with adjuvant chemotherapy, partial remission in 3/14. Successful down-staging could be achieved in 4/8 patients with neo-adjuvant chemotherapy. The PIPS is suitable for repeated ILC which may be a valuable method for pre- and post-surgical therapy of advanced or high-risk cervical and endometrial cancer, for adjuvant chemotherapy as well as neo-adjuvantly for down-staging, or for palliation
Recurrent endometrial cancer: patterns of recurrent disease and assessment of prognosis
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Sohaib, S.A. [Department of Radiology, Royal Marsden Hospital, London (United Kingdom); Houghton, S.L. [Department of Radiology, Royal Marsden Hospital, London (United Kingdom); Meroni, R. [Department of Academic Radiology, St Bartholomew' s Hospital, London (United Kingdom); Rockall, A.G. [Department of Academic Radiology, St Bartholomew' s Hospital, London (United Kingdom); Blake, P. [Department of Gynaecological Oncology, Royal Marsden Hospital, London (United Kingdom); Reznek, R.H. [Department of Academic Radiology, St Bartholomew' s Hospital, London (United Kingdom)
2007-01-15
Aim: To evaluate patterns of disease and identify factors predicting outcome in patients presenting with recurrent endometrial adenocarcinoma following primary surgery. Materials and methods: A retrospective review was performed of the imaging and clinical data in 86 patients (median age 66 years, range 42-88 years) presenting with recurrent endometrial adenocarcinoma following primary surgery. Results: Following primary surgery recurrent disease occurred within 2 years in 64% and within 3 years in 87%. Relapse was seen within lymph nodes in 41 (46%), the vagina in 36 (42%) the peritoneum in 24 (28%) and the lung in 21 (24%). Unusual sites of disease included spleen, pancreas, rectum, muscle and brain. Univariate survival analysis showed the factors significant for poor outcome were: multiple sites of disease, liver and splenic disease, haematogenous, peritoneal and nodal spread, poorly differentiated tumour, and early relapse. The presence of disease within the vagina, bladder or lung was not associated with poor prognosis. Multivariate analysis identified multiple sites of disease, liver and splenic metastases to be independent predictors of poor outcome. Conclusion: The most frequently observed sites of relapse are: lymph nodes, vagina, peritoneum and lung. Significant predictors of poor outcome in recurrent disease are multiple sites of disease and liver and splenic metastases.
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Alli Straubhar
2017-08-01
Full Text Available Introduction: Young women with endometrial intraepithelial hyperplasia or low-grade endometrial carcinoma are potential candidates for conservative fertility sparing therapy utilizing progesterone rather than hysterectomy. High-dose progesterone treatment is associated with 55–80% initial response but high relapse rates. Using aromatase inhibitors in conjunction with high-dose progesterone has largely been unstudied. Case descriptions: Three obese premenopausal women with endometrial cancer failed to respond to oral or intrauterine progesterone as first line therapy. Due to their desire to continue to pursue fertility sparing treatment options, an aromatase inhibitor was added to their treatment regimen. This resulted in resolution of their malignancy in each case. Discussion: In obese premenopausal women, the mechanism of malignant transformation in endometrial carcinoma is considered to be an association with relatively high levels of serum estrogen from peripheral conversion of androgens to estrone in adipose tissue with a deficiency in progesterone exposure due to chronic anovulation. Using aromatase inhibitors seems reasonable as an adjunct to progesterone given the high likelihood that this population has a significant proportion of their estrogen production coming from peripheral conversion in adipose tissue. This case series is unique in that each woman initially failed to respond to progesterone but had resolution when an aromatase inhibitor was added to their treatment regimen. This would suggest that obese women with low grade malignancy or hyperplasia who have no radiographic evidence of deep myometrial invasion, ovarian or retroperitoneal metastases and who wish to retain their fertility may be treated with intrauterine progesterone and an aromatase inhibitor.
Yinghua Li; Yunpeng Xie; Dan Cui; Yanni Ma; Linlin Sui; Chenyang Zhu; Hui Kong; Ying Kong
2015-01-01
Background/Aims: Osteopontin (OPN) is an Extracellular Matrix (ECM) molecule and is involved in many physiologic and pathologic processes, including cell adhesion, angiogenesis and tumor metastasis. OPN is a well-known multifunctional factor involved in various aspects of cancer progression, including endometrial cancer. In this study, we examined the significance of OPN in endometrial cancer. Methods: The proliferation, migration and invasion ability of HEC-1A cells were detected by Cell Cou...
Concurrent Endometrial Carcinoma in Patients with a Curettage Diagnosis of Endometrial Hyperplasia
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Yu-Li Chen
2009-06-01
Conclusion: When patients are diagnosed with endometrial hyperplasia, surgical intervention should be performed in those with cytological atypia and higher BMI because of the possibility of coexisting endometrial carcinoma.
Buchanan, Daniel D; Tan, Yen Y; Walsh, Michael D; Clendenning, Mark; Metcalf, Alexander M; Ferguson, Kaltin; Arnold, Sven T; Thompson, Bryony A; Lose, Felicity A; Parsons, Michael T; Walters, Rhiannon J; Pearson, Sally-Ann; Cummings, Margaret; Oehler, Martin K; Blomfield, Penelope B; Quinn, Michael A; Kirk, Judy A; Stewart, Colin J; Obermair, Andreas; Young, Joanne P; Webb, Penelope M; Spurdle, Amanda B
2014-01-10
Clinicopathologic data from a population-based endometrial cancer cohort, unselected for age or family history, were analyzed to determine the optimal scheme for identification of patients with germline mismatch repair (MMR) gene mutations. Endometrial cancers from 702 patients recruited into the Australian National Endometrial Cancer Study (ANECS) were tested for MMR protein expression using immunohistochemistry (IHC) and for MLH1 gene promoter methylation in MLH1-deficient cases. MMR mutation testing was performed on germline DNA of patients with MMR-protein deficient tumors. Prediction of germline mutation status was compared for combinations of tumor characteristics, age at diagnosis, and various clinical criteria (Amsterdam, Bethesda, Society of Gynecologic Oncology, ANECS). Tumor MMR-protein deficiency was detected in 170 (24%) of 702 cases. Germline testing of 158 MMR-deficient cases identified 22 truncating mutations (3% of all cases) and four unclassified variants. Tumor MLH1 methylation was detected in 99 (89%) of 111 cases demonstrating MLH1/PMS2 IHC loss; all were germline MLH1 mutation negative. A combination of MMR IHC plus MLH1 methylation testing in women younger than 60 years of age at diagnosis provided the highest positive predictive value for the identification of mutation carriers at 46% versus ≤ 41% for any other criteria considered. Population-level identification of patients with MMR mutation-positive endometrial cancer is optimized by stepwise testing for tumor MMR IHC loss in patients younger than 60 years, tumor MLH1 methylation in individuals with MLH1 IHC loss, and germline mutations in patients exhibiting loss of MSH6, MSH2, or PMS2 or loss of MLH1/PMS2 with absence of MLH1 methylation.
Endometrial carcinoma: merit of magnetic resonance in pre-surgical staging
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Fernandez, E.; Barrera, M. C.; Gervas, C.; Salvador, E.; Rivero, B.; Sentis, M.
2003-01-01
To evaluate MR capacity in assessing deep myometrial and cervical infiltrations in cases of endometrial carcinoma. A series of 30 consecutively diagnosed endometrial cancer patients was pre-surgically evaluated by means of magnetic resonance (MR). TSE-T2 sequences with fat saturation and dynamic FFe sequence were used after gadolinium administration. A correlation with post-surgical histological stating was made. There were then determined sensitivity (S), specificity (SP), positive predictive value (PPV) and negative predictive value (NPV) for the deep myometrial infiltration and cervical invasion. Cases of overestimation and underestimation were analyzed. Values obtained for myometrium and cervix were, respectively, S of 67% and 63%, SP of 89% and 91%, PPV of 80% and 71% and NPV of 80% and 87%. Two cases each were over valued for myometrial infiltration and cervix: four cases and 3 cases, respectively, were undervalues. MR stating in cases of endometrial carcinoma is a highly reliable diagnostic technique, but it does present certain limitations. (Author) 19 refs
Efficacy of megestrol acetate in treatment of 21 young patients with endometrial adenocarcinoma
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Eftekhar Z
2007-05-01
Full Text Available Background: Endometrial cancer is the most common malignancy of genital system which is commonly seen after menopause. Rises in the age of marriage non-surgical methods, using systemic progestins, have been evaluated to treat the young patients with well-differentiated endometrial cancer who wish to preserve their fertility. Methods: Twenty one infertile patients with stage Ia well-differentiated endometrial adenocarcinoma were enrolled in a quasi-experimental study. The treatment initiated with 160mg/d of megestrol acetate then continued with 320mg/d for non-responsive cases. Patients follow up with FD&C and hysteroscopy. Patients divided in two groups on the basis of response to therapy and persistent. The responsive patients were introduced to IVF group and evaluated for later fertility and birth of alive newborns for three years. Results: This study showed a response rate of 85.71% and 14.29% undergoing TAH. The mean duration of treatment was 5.85±2.00 month. The response to therapy was observed in 27.78% with dose of 160mg/d and the remaining patients with 320mg/d. Pregnancy occurred in 27.78%, 2 of which ended up in a term delivery and the others ended before term. Recurrence happened in 16.67% that 66.67% of them experienced remission again. Conclusion: Use of 320mg/d seems to be associated with a better therapeutic response. Serious complications were not observed with this dose. Furthermore, continuance of the drug for three month following a normal pathology report was decreased the rate of recurrence.
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Hori, Masatoshi; Kim, Tonsok; Onishi, Hiromitsu; Nakamoto, Atsushi; Tomiyama, Noriyuki [Osaka University Graduate School of Medicine, Department of Radiology, Suita, Osaka (Japan); Imaoka, Izumi; Kagawa, Yuki; Murakami, Takamichi [Kinki University School of Medicine, Department of Radiology, Osaka (Japan); Ueguchi, Takashi; Tatsumi, Mitsuaki [Osaka University Hospital, Department of Radiology, Osaka (Japan); Enomoto, Takayuki [Osaka University Graduate School of Medicine, Department of Obstetrics and Gynecology, Osaka (Japan); Niigata University School of Medicine, Department of Obstetrics and Gynecology, Niigata (Japan); Kimura, Tadashi [Osaka University Graduate School of Medicine, Department of Obstetrics and Gynecology, Osaka (Japan)
2013-08-15
To prospectively assess the efficacy of 3-T magnetic resonance (MR) imaging using the three-dimensional turbo spin-echo T2-weighted and diffusion-weighted technique (3D-TSE/DW) compared with that of conventional imaging using the two-dimensional turbo spin-echo T2-weighted and dynamic contrast-enhanced technique (2D-TSE/DCE) for the preoperative staging of endometrial cancer, with pathological analysis as the reference standard. Seventy-one women with endometrial cancer underwent MR imaging using 3D-TSE/DW (b = 1,000 s/mm{sup 2}) and 2D-TSE/DCE. Two radiologists independently assessed the two imaging sets. Accuracy, sensitivity, and specificity for staging were analysed with the McNemar test; the areas under the receiver operating characteristic curve (Az) were compared with a univariate z-score test. The results for assessing deep myometrial invasion, accuracy, sensitivity, specificity and Az, respectively, were as follows: 3D-TSE/DW - observer 1, 87 %, 95 %, 85 % and 0.96; observer 2, 92 %, 84 %, 94 % and 0.95; 2D-TSE/DCE - observer 1, 80 %, 79 %, 81 % and 0.89; observer 2, 86 %, 84 %, 87 % and 0.86. Most of the values were higher with 3D-TSE/DW without significant differences (P > 0.12). For assessing cervical stromal invasion, there were no significant differences in those values for both observers (P > 0.6). Accuracy of 3D-TSE/DW was at least equivalent to that of the conventional technique for the preoperative assessment of endometrial cancer. (orig.)
Life after endometrial cancer: A systematic review of patient-reported outcomes.
Shisler, Robert; Sinnott, Jennifer A; Wang, Vivian; Hebert, Courtney; Salani, Ritu; Felix, Ashley S
2018-02-01
Women with endometrial cancer (EC) are the second largest population of female cancer survivors in the United States. However, the outcomes of EC survivors, from the patient perspective, are not well-understood. Therefore, we conducted a systematic review of patient-reported outcomes (PROs) following an EC diagnosis. We searched MEDLINE, EMBASE, Scopus, CINAHL, and reference lists to identify published observational studies that examined PROs among women with EC. Reviewers independently reviewed eligible full-text study articles and conducted data extraction. We qualitatively summarized included articles according to exposures [e.g. body mass index (BMI), treatment, etc.] or specific PROs (e.g. sexual function). Of 1722 unique studies, 102 full-text articles were reviewed, of which a total of 27 studies fulfilled the inclusion criteria. The most commonly used PRO questionnaires were the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) (n=9), Short Form 36 Questionnaire (SF-36, n=8), the Functional Assessment of Cancer Therapy-General (FACT-G, n=5), and the Female Sexual Function Index (FSFI, n=4). Obesity was associated with lower quality of life (QOL) and physical functioning. Treatment type affected several outcomes. Laparoscopy generally resulted in better QOL outcomes than laparotomy. Likewise, vaginal brachytherapy was associated with better outcomes compared to external beam radiation. Sexual function outcomes were dependent on age, time since diagnosis, and having consulted a physician before engaging in sexual activities. In addition, a physical activity intervention was associated with improved sexual interest but not sexual function. Our review provides insight into the experience of EC survivors from the patient perspective. Factors that contribute to QOL, such as pain, fatigue, emotional and social functioning, should be monitored following an EC diagnosis. Copyright © 2017 Elsevier Inc
Primary Endometrial Squamous Cell Carcinoma In Situ; Report of a rare disease
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Sujata Jetley
2015-11-01
Full Text Available Squamous cell carcinoma (SCC of the endometrium, whether primary or secondary to cervical cancer, is a rare entity. Primary endometrial squamous cell carcinoma in situ is even more uncommon; it usually occurs in postmenopausal women and has a strong association with pyometra. We report a 60-year-old multiparous postmenopausal woman who presented to the Hakeem Abdul Hameed Centenary Hospital, New Delhi, India, in May 2014 with a lower abdominal swelling corresponding in size to a pregnancy of 26 gestational weeks and vaginal discharge of one year’s duration. A total abdominal hysterectomy with a bilateral salpingooophorectomy was performed, which revealed an enlarged uterus with pyometra. Histopathology showed that the entire endometrial lining had been replaced with malignant squamous cells without invasion of the myometrium. Immunohistochemistry revealed that the tumour cells were positive for p63 with a high Ki-67 labelling index. No adjuvant therapy was required and the patient was disease-free at a seven-month follow-up.
Primary Endometrial Squamous Cell Carcinoma In Situ: Report of a rare disease.
Jetley, Sujata; Jairajpuri, Zeeba S; Hassan, Mohammad J; Madaan, Garima; Jain, Reena
2015-11-01
Squamous cell carcinoma (SCC) of the endometrium, whether primary or secondary to cervical cancer, is a rare entity. Primary endometrial squamous cell carcinoma in situ is even more uncommon; it usually occurs in postmenopausal women and has a strong association with pyometra. We report a 60-year-old multiparous postmenopausal woman who presented to the Hakeem Abdul Hameed Centenary Hospital, New Delhi, India, in May 2014 with a lower abdominal swelling corresponding in size to a pregnancy of 26 gestational weeks and vaginal discharge of one year's duration. A total abdominal hysterectomy with a bilateral salpingooophorectomy was performed, which revealed an enlarged uterus with pyometra. Histopathology showed that the entire endometrial lining had been replaced with malignant squamous cells without invasion of the myometrium. Immunohistochemistry revealed that the tumour cells were positive for p63 with a high Ki-67 labelling index. No adjuvant therapy was required and the patient was disease-free at a seven-month follow-up.
Ozer, Alev; Ozer, Serdar; Kanat-Pektas, Mine
2016-05-01
The present study aims to determine how transvaginal ultrasonography and histopathological examination findings are correlated in a cohort of premenopausal and postmenopausal Turkish women with abnormal uterine bleeding. This is a retrospective review of 350 Turkish women who underwent transvaginal ultrasonography and suction curettage as a result of abnormal uterine bleeding. Sonographic appearance of the endometrium was normal in 244 patients (69.7%), while homogeneous thickening was detected in 47 patients (13.4%) and cystic thickening in 21 patients (6.0%). A sonographic diagnosis of endometrial polyp was made in 38 patients (10.9%). Histopathological analysis of endometrial samplings revealed proliferative endometrium (36%), secretory endometrium (24.6%), decidualization (10.9%), endometrial polyp (8.3%), endometritis (6.8%), endometrial hyperplasia (4.6%), irregular shedding (3.7%), atrophic endometrium (3.1%), endometrial cancer (1.1%) and placental retention (0.9%). The sonographic and histopathological findings correlated significantly (χ(2) = 122 768, P = 0.001; r = 0.215, P = 0.001). Approximately 51% of the women with homogeneous endometrial thickening had proliferative endometrium. Only 44.7% of the women with ultrasonographically visualized endometrial polyps had histopathologically diagnosed endometrial polyps. Nearly 57% of the women with cystic endometrial thickening had proliferative endometrium. If there is no facility for hysteroscopy or hysteroscopy-guided endometrial biopsy for women with abnormal uterine bleeding, transvaginal ultrasonography findings can be efficiently used to make a preliminary diagnosis and, thus, notify the pathologists. © 2016 Japan Society of Obstetrics and Gynecology.
Vassallo, Pierre
2012-01-01
"nAbnormal uterine bleeding, whether in peri menopausal or postmenopausal patients, is an important clinical concern and results in much medical intervention. When bleeding occurs in women over 40 years of age as well as any postmenopausal women, endometrial assessment is mandatory. In the past and present, many clinicians prefer to begin such assessment with blind endometrial sampling. However, when an ultrasound-based approach to such patients is present, a thin distinct end...
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Kitajima, Kazuhiro; Suenaga, Yuko; Ueno, Yoshiko; Kanda, Tomonori; Maeda, Tetsuo; Takahashi, Satoru; Ebina, Yasuhiko; Miyahara, Yoshiya; Yamada, Hideto; Sugimura, Kazuro
2013-01-01
Purpose: To investigate the diagnostic value of retrospective fusion of pelvic MRI and 18 F-fluorodeoxyglucose ( 18 F-FDG) PET images for assessment of locoregional extension and nodal staging of endometrial cancer. Materials and methods: Thirty patients with biopsy-proven endometrial cancer underwent preoperative contrast-enhanced PET/CT (PET/ceCT) and pelvic dynamic contrast-enhanced MRI for initial staging. Diagnostic performance of PET/ceCT, contrast-enhanced MRI, and retrospective image fusion from PET and MRI (fused PET/MRI) for assessing the extent of the primary tumor (T stage) and metastasis to regional LNs (N stage) was evaluated by two experienced readers. Histopathological and follow-up imaging results were used as the gold standard. The McNemar test was employed for statistical analysis. Results: Fused PET/MRI and MRI detected 96.7% of the primary tumors, whereas PET/ceCT detected 93.3%. Accuracy for T status was 80.0% for fused PET/MRI, and MRI proved significantly more accurate than PET/ceCT, which had an accuracy of 60.0% (p = 0.041). Patient-based sensitivity, specificity and accuracy for detecting pelvic nodal metastasis were 100%, 96.3% and 96.7% for both fused PET/MRI and PET/ceCT, and 66.7%, 100% and 96.7% for MRI, respectively. These three parameters were not statistically significant (p = 1). Conclusion: Fused PET/MRI, which complements the individual advantages of MRI and PET, is a valuable technique for assessment of the primary tumor and nodal staging in patients with endometrial cancer
... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... cancer cells have places where hormones can attach ( receptors ), drugs , surgery, or radiation therapy is used to ...
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Seeber, Laura MS; Horrée, Nicole; Groep, Petra van der; Wall, Elsken van der; Verheijen, René HM; Diest, Paul J van
2010-01-01
Hypoxia inducible factor 1α (HIF-1α) plays an essential role in the adaptive response of cells to hypoxia and is associated with aggressive tumour behaviour. We have shown p27 kip1 , which is generally reduced in endometrial cancer, to be re-expressed in hypoxic regions. This possibly contributes to survival of cancer cells. The aim of this study was to evaluate the prognostic value of HIF-1α and p27 kip expression in patients with endometrioid endometrial cancer. Expression levels of HIF-1α, CAIX, Glut-1, and p27 kip1 were analyzed by immunohistochemistry. Percentage of positive cells, staining pattern (perinecrotic, diffuse, or mixed) and presence of necrosis were noted. Necrosis was correlated with shortened disease free survival (DFS) (p = 0.008) and overall survival (OS) (p = 0.045). For DFS, perinecrotic HIF-1α expression was also prognostic (p = 0.044). Moreover, high p27 kip1 expression was an additional prognostic factor for these patients with perinecrotic HIF-1α expression. In multivariate Cox regression, perinecrotic HIF-expression emerged as an independent prognostic factor. Perinecrotic HIF-1α expression was significantly associated with CAIX and Glut-1 expression, pointing towards functional HIF-1. In patients with endometrioid endometrial cancer, necrosis and necrosis-related expression of HIF-1α are important prognostic factors. More aggressive adjuvant treatment might be necessary to improve the outcome of patients with these characteristics
Wang, Jing; Liu, Yao; Wang, Lihua; Sun, Xiao; Wang, Yudong
2016-02-02
RANK/RANKL plays a key role in metastasis of certain malignant tumors, which makes it a promising target for developing novel therapeutic strategies for cancer. However, the prognostic value and pro-metastatic activity of RANK in endometrial cancer (EC) remain to be determined. Thus, the present study investigated the effect of RANK on the prognosis of EC patients, as well as the pro-metastatic activity of EC cells. The results indicated that those with high expression of RANK showed decreased overall survival and progression-free survival. Statistical analysis revealed the positive correlations between RANK/RANKL expression and metastasis-related factors. Additionally, RANK/RANKL significantly promoted cell migration/invasion via activating AKT/β-catenin/Snail pathway in vitro. However, RANK/RANKL-induced AKT activation could be suppressed after osteoprotegerin (OPG) treatment. Furthermore, the combination of medroxyprogesterone acetate (MPA) and RANKL could in turn attenuate the effect of RANKL alone. Similarly, MPA could partially inhibit the RANK-induced metastasis in an orthotopic mouse model via suppressing AKT/β-catenin/Snail pathway. Therefore, therapeutic inhibition of MPA in RANK/RANKL-induced metastasis was mediated by AKT/β-catenin/Snail pathway both in vitro and in vivo, suggesting a potential target of RANK for gene-based therapy for EC.
Talhouk, Aline; Hoang, Lien N; McConechy, Melissa K; Nakonechny, Quentin; Leo, Joyce; Cheng, Angela; Leung, Samuel; Yang, Winnie; Lum, Amy; Köbel, Martin; Lee, Cheng-Han; Soslow, Robert A; Huntsman, David G; Gilks, C Blake; McAlpine, Jessica N
2016-10-01
Categorization and risk stratification of endometrial carcinomas is inadequate; histomorphologic assessment shows considerable interobserver variability, and risk of metastases and recurrence can only be derived after surgical staging. We have developed a Proactive Molecular Risk classification tool for Endometrial cancers (ProMisE) that identifies four distinct prognostic subgroups. Our objective was to assess whether molecular classification could be performed on diagnostic endometrial specimens obtained prior to surgical staging and its concordance with molecular classification performed on the subsequent hysterectomy specimen. Sequencing of tumors for exonuclease domain mutations (EDMs) in POLE and immunohistochemistry for mismatch repair (MMR) proteins and p53 were applied to both pre- and post-staging archival specimens from 60 individuals to identify four molecular subgroups: MMR-D, POLE EDM, p53 wild type, p53 abn (abnormal). Three gynecologic subspecialty pathologists assigned histotype and grade to a subset of samples. Concordance of molecular and clinicopathologic subgroup assignments were determined, comparing biopsy/curetting to hysterectomy specimens. Complete molecular and pathologic categorization was achieved in 57 cases. Concordance metrics for pre- vs. post-staging endometrial samples categorized by ProMisE were highly favorable; average per ProMisE class sensitivity(0.9), specificity(0.96), PPV(0.9), NPV(0.96) and kappa statistic 0.86(95%CI, 0.72-0.93), indicating excellent agreement. We observed the highest level of concordance for 'p53 abn' tumors, the group associated with the worst prognosis. In contrast, grade and histotype assignment from original pathology reports pre- vs. post-staging showed only moderate levels of agreement (kappa=0.55 and 0.44 respectively); even with subspecialty pathology review only moderate levels of agreement were observed. Molecular classification can be achieved on diagnostic endometrial samples and accurately
Liu, Zhao; Qi, Shasha; Zhao, Xingbo; Li, Mingjiang; Ding, Sentai; Lu, Jiaju; Zhang, Hui
2016-01-01
The potential role of metformin in treating endometrial cancer remains to be explored. The current study investigated the role of metformin in 17?-estradiol-induced epithelial-mesenchymal transition (EMT) in endometrial adenocarcinoma cells. We found that 17?-estradiol promoted proliferation and migration, attenuated apoptosis in both estrogen receptor (ER) positive and ER negative endometrial adenocarcinoma cells (Ishikawa and KLE cells, respectively). Metformin abolished 17?-estradiol-induc...
Kikalishvili, N; Beriashvili, R; Muzashvili, T; Burkadze, G
2018-03-01
Endometrial neoplasia is the most common malignant tumor of female genital system in developed countries. The incidence of endometrial cancer has increased in the last years and despite advances in diagnosis and treatment, the death rates have steadily been increasing over the past 20 years. Therefore aspects of endometrial cancer development, pathogenesis and effective treatment is especially urgent to this day, as much of the risk for endometrial cancer development is influenced by the environment and lifestyle. Endometrial stem cells take the special place among somatic stem cells of female reproductive system-the detection of them and identification of their location in the complex cellular hierarchy still remains challenging. Further study of endometrial stem cells will clarify their role in gynecologic pathologies associated with hyper-proliferative states of endometrium. The aim of our study was to explore the specificities of endometrial proliferative/stem cell index distribution under endometrioid carcinoma of different grade of malignancy. The study represents a retrospective research. The coded and depersonalized material data from Acad. N. Kipshidze Central University Clinic was used in the study. 3 study groups - 1st study group "Endometrioid Carcinoma Grade 1" (14 cases), 2nd study group "Endometrioid Carcinoma Grade 2" (23 cases) and 3rd study group "Endometrioid Carcinoma Grade 3" were selected from routine histopathology tissue specimens of uterus. Hematoxilyn-eosin technology and immunohistochemistry with proliferation marker ki67 and stem cell marker CD146 was performed. The proliferative/stem cell index was calculated by the ratio of Ki67-positive cell percentage value divided by CD146-positive cell percentage value. The study showed that in the 1st study group labeled as "Endometrioid Carcinoma Grade 1", the proliferative/stem cell index ranges between 21.7 and 25.5. Its mean average value in the age distribution subgroups accounts for: 1
The value of diagnostic hysteroscopy with biopsy in the preoperative of endometrial ablation
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Salete Yatabe
2011-12-01
Full Text Available Objective: To assess the value of diagnostic hysteroscopy with biopsy in the preoperative preparation for endometrial ablation. Methods: It was a prospective non-randomized study conducted at the division of Gynecologic Endoscopy of Hospital do Servidor Público Estadual “Francisco Morato de Oliveira” from March 2007 to May 2009. A total of 45 patients with abnormal uterine bleeding, and referred to endometrial ablation were included. All women underwent a diagnostic hysteroscopy, and were treated with a GnRH analogous – goserelin – 10.8 mg before surgery. The endometrial ablation was performed with a surgical resectoscope. Patients were submitted to one directed endometrial biopsy, one guided endometrial biopsy with Novak curette, and to endometrial ablation, which was considered as reference for pathological examination with samples from the biopsies. Data were analyze using the SPSS-v16 software, and considered significance at p = 0.05. Results: The mean age of women was 44.20 years (33-56, parity of 2.67 (0-9, uterus size of 139.99 calculated in cc (42-278, and the mean duration of symptoms was 3.68 years (0.5-15. The guided endometrial biopsy showed sensitivity of 80% for endometrium without atypia, and the directed endometrial biopsy had sensitivity of 60%. For proliferative endometrium the directed endometrial biopsy showed sensitivity of 76 and 100% for secretory endometrium, which was higher than the guided endometrial biopsy with 53 and 50%, respectively. Conclusion: The directed biopsy before endometrial ablation had lower sensitivity than guided biopsy for endometrium without atypia, however it was higher for proliferative and secretory endometrium.
Özdemir, Suna; Batmaz, Gonca; Ates, Seda; Celik, Cetin; Incesu, Feyzanur; Peru, Celalettin
2015-01-01
We aimed to investigate the association of metabolic syndrome and metabolic risk factors with endometrial hyperplasia and carcinoma among women with abnormal uterine bleeding (AUB). This study included 199 patients who had undergone endometrial curettage due to abnormal uterine bleeding. We divided the patients into two groups according to whether they had an abnormal (n = 53) or normal endometrium (n = 146). Waist circumference, blood pressure, fasting glucose and serum lipid levels were measured and statistically analyzed. The women in each group were matched with regard to mean age, gravidity, parity and menopausal status. We found increased prevalence of metabolic syndrome, diabetes, general and abdominal obesity, hypertension, elevated levels of glucose, total cholesterol and LDL-cholesterol and reduced levels of HDL-cholesterol among women with endometrial carcinoma and hyperplasia. These results were detected particularly in postmenopausal (>50 years) women compared to pre-menopausal cases (<50 years). All metabolic parameters were similar between hyperplasia and cancer groups. Metabolic syndrome and its components have been shown to have profound impacts on initiation and progession of endometrial pathology, particularly during post-menopausal period.
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Cho, Hanbyoul; Nam, Byung-Ho; Kim, Seok Mo; Cho, Chi-Heum; Kim, Byoung Gie; Ryu, Hee-Sug; Kang, Soon Beom; Kim, Jae-Hoon
2014-01-01
Purpose: A phase 2 study was completed by the Korean Gynecologic Oncologic Group to evaluate the efficacy and toxicity of concurrent chemoradiation with weekly paclitaxel in patients with high-risk endometrial cancer. Methods and Materials: Pathologic requirements included endometrial endometrioid adenocarcinoma stages III and IV. Radiation therapy consisted of a total dose of 4500 to 5040 cGy in 5 fractions per week for 6 weeks. Paclitaxel 60 mg/m 2 was administered once weekly for 5 weeks during radiation therapy. Results: Fifty-seven patients were enrolled between January 2006 and March 2008. The median follow-up time was 60.0 months (95% confidence interval [CI], 51.0-58.2). All grade 3/4 toxicities were hematologic and usually self-limited. There was no life-threatening toxicity. The cumulative incidence of intrapelvic recurrence sites was 1.9% (1/52), and the cumulative incidence of extrapelvic recurrence sites was 34.6% (18/52). The estimated 5-year disease-free and overall survival rates were 63.5% (95% CI, 50.4-76.5) and 82.7% (95% CI, 72.4-92.9), respectively. Conclusions: Concurrent chemoradiation with weekly paclitaxel is well tolerated and seems to be effective for high-risk endometrioid endometrial cancers. This approach appears reasonable to be tested for efficacy in a prospective, randomized controlled study
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Cho, Hanbyoul [Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of); Institute of Women' s Life Medical Science, Yonsei University College of Medicine, Seoul (Korea, Republic of); Nam, Byung-Ho [Cancer Biostatistics Branch, Research Institute for National Cancer Control and Evaluation, National Cancer Center, Goyang (Korea, Republic of); Kim, Seok Mo [Department of Obstetrics and Gynecology, Chonnam National University School of Medicine, Gwangju (Korea, Republic of); Cho, Chi-Heum [Department of Obstetrics and Gynecology, Keimyung University School of Medicine, Daegu (Korea, Republic of); Kim, Byoung Gie [Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Ryu, Hee-Sug [Department of Obstetrics and Gynecology, Ajou University School of Medicine, Suwon (Korea, Republic of); Kang, Soon Beom [Department of Obstetrics and Gynecology, Konkuk University School of Medicine, Seoul (Korea, Republic of); Kim, Jae-Hoon, E-mail: jaehoonkim@yuhs.ac [Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of); Institute of Women' s Life Medical Science, Yonsei University College of Medicine, Seoul (Korea, Republic of)
2014-09-01
Purpose: A phase 2 study was completed by the Korean Gynecologic Oncologic Group to evaluate the efficacy and toxicity of concurrent chemoradiation with weekly paclitaxel in patients with high-risk endometrial cancer. Methods and Materials: Pathologic requirements included endometrial endometrioid adenocarcinoma stages III and IV. Radiation therapy consisted of a total dose of 4500 to 5040 cGy in 5 fractions per week for 6 weeks. Paclitaxel 60 mg/m{sup 2} was administered once weekly for 5 weeks during radiation therapy. Results: Fifty-seven patients were enrolled between January 2006 and March 2008. The median follow-up time was 60.0 months (95% confidence interval [CI], 51.0-58.2). All grade 3/4 toxicities were hematologic and usually self-limited. There was no life-threatening toxicity. The cumulative incidence of intrapelvic recurrence sites was 1.9% (1/52), and the cumulative incidence of extrapelvic recurrence sites was 34.6% (18/52). The estimated 5-year disease-free and overall survival rates were 63.5% (95% CI, 50.4-76.5) and 82.7% (95% CI, 72.4-92.9), respectively. Conclusions: Concurrent chemoradiation with weekly paclitaxel is well tolerated and seems to be effective for high-risk endometrioid endometrial cancers. This approach appears reasonable to be tested for efficacy in a prospective, randomized controlled study.
PTEN Sequence Analysis in Endometrial Hyperplasia and Endometrial Carcinoma in Slovak Women
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H. Gbelcová
2015-01-01
Full Text Available Phosphatase and tensin homolog (PTEN is a protein that acts as a tumor suppressor by dephosphorylating the lipid second messenger phosphatidylinositol 3,4,5-trisphosphate. Loss of PTEN function has been implicated in the pathogenesis of a number of different tumors, particularly endometrial carcinoma (ECa. ECa is the most common neoplasia of the female genital tract. Our study evaluates an association between the morphological appearance of endometrial hyperplasia and endometrial carcinoma and the degree of PTEN alterations. A total of 45 endometrial biopsies from Slovak women were included in present study. Formalin-fixed and paraffin-embedded tissue samples with simple hyperplasia (3, complex hyperplasia (5, atypical complex hyperplasia (7, endometrioid carcinomas G1 (20 and G3 (5, and serous carcinoma (5 were evaluated for the presence of mutations in coding regions of PTEN gene, the most frequently mutated tumor suppressor gene in endometrial carcinoma. 75% of the detected mutations were clustered in exons 5 and 8. Out of the 39 mutations detected in 24 cases, 20 were frameshifts and 19 were nonsense, missense, or silent mutations. Some specimens harboured more than one mutation. The results of current study on Slovak women were compared to a previous study performed on Polish population. The two sets of results were similar.
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Kitajima, Kazuhiro, E-mail: kitajima@med.kobe-u.ac.jp [Department of Radiology, Kobe University School of Medicine, Kobe (Japan); Suenaga, Yuko; Ueno, Yoshiko [Department of Radiology, Kobe University School of Medicine, Kobe (Japan); Kanda, Tomonori [Department of Obsterics and Gynecology of Kobe University School of Medicine, Kobe (Japan); Department of Radiology, Hyogo Cancer Center, Hyogo (Japan); Maeda, Tetsuo; Takahashi, Satoru [Department of Radiology, Kobe University School of Medicine, Kobe (Japan); Ebina, Yasuhiko; Miyahara, Yoshiya; Yamada, Hideto [Department of Obsterics and Gynecology of Kobe University School of Medicine, Kobe (Japan); Department of Radiology, Hyogo Cancer Center, Hyogo (Japan); Sugimura, Kazuro [Department of Radiology, Kobe University School of Medicine, Kobe (Japan)
2013-10-01
Purpose: To investigate the diagnostic value of retrospective fusion of pelvic MRI and {sup 18}F-fluorodeoxyglucose ({sup 18}F-FDG) PET images for assessment of locoregional extension and nodal staging of endometrial cancer. Materials and methods: Thirty patients with biopsy-proven endometrial cancer underwent preoperative contrast-enhanced PET/CT (PET/ceCT) and pelvic dynamic contrast-enhanced MRI for initial staging. Diagnostic performance of PET/ceCT, contrast-enhanced MRI, and retrospective image fusion from PET and MRI (fused PET/MRI) for assessing the extent of the primary tumor (T stage) and metastasis to regional LNs (N stage) was evaluated by two experienced readers. Histopathological and follow-up imaging results were used as the gold standard. The McNemar test was employed for statistical analysis. Results: Fused PET/MRI and MRI detected 96.7% of the primary tumors, whereas PET/ceCT detected 93.3%. Accuracy for T status was 80.0% for fused PET/MRI, and MRI proved significantly more accurate than PET/ceCT, which had an accuracy of 60.0% (p = 0.041). Patient-based sensitivity, specificity and accuracy for detecting pelvic nodal metastasis were 100%, 96.3% and 96.7% for both fused PET/MRI and PET/ceCT, and 66.7%, 100% and 96.7% for MRI, respectively. These three parameters were not statistically significant (p = 1). Conclusion: Fused PET/MRI, which complements the individual advantages of MRI and PET, is a valuable technique for assessment of the primary tumor and nodal staging in patients with endometrial cancer.
SOX15 regulates proliferation and migration of endometrial cancer cells.
Rui, Xiaohui; Xu, Yun; Jiang, Xiping; Guo, Caixia; Jiang, Jingting
2017-10-31
The study aimed to investigate the effects of Sry-like high mobility group box 15 ( SOX15 ) on proliferation and migration of endometrial cancer (EC) cells. Immunohistochemistry (IHC) was applied to determine the expression of SOX15 in EC tissues and adjacent tissues. We used cell transfection method to construct the HEC-1-A and Ishikawa cell lines with stable overexpression and low expression SOX15 Reverse-transcription quantitative real-time PCR (RT-qPCR) and Western blot were performed to examine expression of SOX15 mRNA and SOX15 protein, respectively. By conducting a series of cell proliferation assay and migration assay, we analyzed the influence of SOX15 overexpression or low expression on EC cell proliferation and migration. The expression of SOX15 mRNA and protein in EC tissues was significantly lower than that in adjacent tissues. After lentivirus-transfecting SOX15 , the expression level of SOX15 mRNA and protein was significantly increased in cells of SOX15 group, and decreased in sh- SOX15 group. Overexpression of SOX15 could suppress cell proliferation, while down-regulation of SOX15 increased cell proliferation. Flow cytometry results indicated that overexpression of SOX15 induced the ratio of cell-cycle arrest in G 1 stage. In addition, Transwell migration assay results showed that SOX15 overexpression significantly inhibited cell migration, and also down-regulation of SOX15 promoted the migration. As a whole, SOX15 could regulate the proliferation and migration of EC cells and up- regulation of SOX15 could be valuable for EC treatment. © 2017 The Author(s).
van Meurs, Hannah S.; Bleeker, Maaike C. G.; van der Velden, Jacobus; Overbeek, Lucy I. H.; Kenter, Gemma G.; Buist, Marrije R.
2013-01-01
Concurrent presence of endometrial hyperplasia or cancer in patients with granulosa cell tumors (GCTs) is common, with reported incidences of 25.6% to 65.5%. Consequently, bilateral salpingo-oophorectomy and hysterectomy is usually recommended in patients with a GCT, but this remains debatable. Our
Accuracy of Endometrial Sampling in Endometrial Carcinoma: A Systematic Review and Meta-analysis.
Visser, Nicole C M; Reijnen, Casper; Massuger, Leon F A G; Nagtegaal, Iris D; Bulten, Johan; Pijnenborg, Johanna M A
2017-10-01
To assess the agreement between preoperative endometrial sampling and final diagnosis for tumor grade and subtype in patients with endometrial carcinoma. MEDLINE, EMBASE, ClinicalTrials.gov, and the Cochrane library were searched from inception to January 1, 2017, for studies that compared tumor grade and histologic subtype in preoperative endometrial samples and hysterectomy specimens. In eligible studies, the index test included office endometrial biopsy, hysteroscopic biopsy, or dilatation and curettage; the reference standard was hysterectomy. Outcome measures included tumor grade, histologic subtype, or both. Two independent reviewers assessed the eligibility of the studies. Risk of bias was assessed (Quality Assessment of Diagnostic Accuracy Studies). A total of 45 studies (12,459 patients) met the inclusion criteria. The pooled agreement rate on tumor grade was 0.67 (95% CI 0.60-0.75) and Cohen's κ was 0.45 (95% CI 0.34-0.55). Agreement between hysteroscopic biopsy and final diagnosis was higher (0.89, 95% CI 0.80-0.98) than for dilatation and curettage (0.70, 95% CI 0.60-0.79; P=.02); however, it was not significantly higher than for office endometrial biopsy (0.73, 95% CI 0.60-0.86; P=.08). The lowest agreement rate was found for grade 2 carcinomas (0.61, 95% CI 0.53-0.69). Downgrading was found in 25% and upgrading was found in 21% of the endometrial samples. Agreement on histologic subtypes was 0.95 (95% CI 0.94-0.97) and 0.81 (95% CI 0.69-0.92) for preoperative endometrioid and nonendometrioid carcinomas, respectively. Overall there is only moderate agreement on tumor grade between preoperative endometrial sampling and final diagnosis with the lowest agreement for grade 2 carcinomas.
Shih, I-Lun; Yen, Ruoh-Fang; Chen, Chi-An; Chen, Bang-Bin; Wei, Shwu-Yuan; Chang, Wen-Chun; Sheu, Bor-Ching; Cheng, Wen-Fang; Tseng, Yao-Hui; Chen, Xin-Jia; Chen, Chi-Hau; Wei, Lin-Hung; Chiang, Ying-Cheng; Torng, Pao-Ling; Yen, Men-Luh; Shih, Tiffany Ting-Fang
2015-12-01
To evaluate the correlation between maximum standardized uptake value (SUVmax ) and minimum apparent diffusion coefficient (ADCmin ) of endometrial cancer derived from an integrated positron emission tomography / magnetic resonance (PET/MR) system and to determine their correlation with pathological prognostic factors. This prospective study was approved by the Institutional Review Board of the hospital, and informed consent was obtained. Between April and December 2014, 47 consecutive patients with endometrial cancer were enrolled and underwent simultaneous PET/MR examinations before surgery. Thirty-six patients with measurable tumors on PET/MR were included for image analysis. Pearson's correlation coefficient was used to evaluate the correlation between SUVmax and ADCmin of the tumors. The Mann-Whitney U-test was utilized to evaluate relationships between these two imaging biomarkers and pathological prognostic factors. The mean SUVmax and ADCmin were 14.7 ± 7.1 and 0.48 ± 0.13 × 10(-3) mm(2) /s, respectively. A significant inverse correlation was found between SUVmax and ADCmin (r = -0.53; P = 0.001). SUVmax was significantly higher in tumors with advanced stage, deep myometrial invasion, cervical invasion, lymphovascular space involvement, and lymph node metastasis (P correlated and are associated with pathological prognostic factors. © 2015 Wiley Periodicals, Inc.
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Zhan-Ying Wang
2015-06-01
Full Text Available Endometrial cancer is one of the most prevalent gynaecological malignancies where, currently available therapeutic options remain limited. Recently phytochemicals are exploited for their efficiency in cancer therapy. The present study investigates the anti-proliferative effect of fisetin, a flavonoid on human endometrial cancer cells (KLE and Hec1 A. Fisetin (20-100 µM effectively reduced the viability of Hec1 A and KLE cells and potentially altered the cell population at G2/M stage. Expression levels of the cell cycle proteins (cyclin B1, p-Cdc2, p-Cdc25C, p-Chk1, Chk2, p-ATM, cyclin B1, H2AX, p21 and p27 were analyzed. Fisetin suppressed cyclin B1 expression and caused inactiva-tion of Cdc25C and Cdc2 by increasing their phosphorylation levels and further activated ATM, Chk1 and Chk2. Increased levels of p21 and p27 were observed as well. These results suggest that fisetin induced G2/M cell cycle arrest via inactivating Cdc25c and Cdc2 through activation of ATM, Chk1 and Chk2.
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Nyholm, H C; Nielsen, A L; Lyndrup, J
1992-01-01
OBJECTIVE: This study investigates clinicopathologic associations of estrogen and progesterone receptor content in endometrial carcinoma. STUDY DESIGN: One hundred fifty-two patients with endometrial cancer and 12 with adenomatous hyperplasia were included. Dextran-coated charcoal receptor assay...... receptor dextran-coated charcoal values and immunohistochemical histologic scores correlated inversely (p dextran-coated charcoal values was independent...
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Erhan Yavuz
2012-12-01
Full Text Available Objective: To demonstrate diagnostic efficacy of endometrial cytologic sampling for detection of endometrial pathologies (endometrial hyperplasias and cancers,by comparing endometrial full curettage and endometrial cytologic smear pathologic results performed in patients with abnormal uterine bleeding. Materials and Methods: Totally 109 reproductive and postmenopausal women with abnormal uterine bleeding who applied our clinic between January 2005-June 2010 were included in the study.After measurement of endometrial thickness by transvaginal ultrasound, patients were treated initialy with endometrial cytologic sampling using endometrial brush then endometrial full curettage using sharp curette.Pathology and cytology reports were evaluated retrospectively. Results: The most frequent diagnoses in endometrial cytologic specimens obtained by endometrial brush was nondiagnostic with a rate of 73.7%(n: 42 and 53.8%(n: 28 in postmenopausal women and reproductive period women, respectively.When all patients were analysed together, diagnosis was nondiagnostic in 64.2%(n: 70 (38.5% postmenopausal,25.7% premenopausalof endometrial cytologic samples.Cytologic assessment was resulted as sufficient in only 35.8% (n: 39 of cases.Endometrial full curettage pathologic diagnoses were resulted as insufficient in 56.1%(n: 32of postmenopausal patients and 9.6%(n: 5 of reproductive period cases.The second most frequent diagnosis was endometrial polyp in 13(22.8% patients in postmenopausal period, whereas the most frequent diagnoses in reproductive period were reported as endometrial polyp in 18(34.6% and secretory endometrium in 12(23.1% patients. When full curettage was considered as golden standard method with respect to sample sufficiency;the sensitivity of endometrial cytologic evaluation in postmenopausal patients with regard to sample sufficiency was found as 36%, spesificity 81.3%, positive predictive value 60.0%, negative predictive value 61.9%; the values
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Chovanec, Josef; Selingerova, Iveta; Greplova, Kristina
2017-01-01
based on single-institution data from 120 EC patients and validated against multicentric data from 379 EC patients. Results: In non-cancer individuals, serum HE4 levels increase log-linearly with reduced glomerular filtration of eGFR = 90 ml/min/1.73 m2. HE4ren, adjusting HE4 serum levels to decreased e...... levels to reduced eGFR that enables quantification of time-dependent changes in HE4 production and elimination irrespective of age and renal function in women. Utilizing HE4ren improves performance of biomarker-based models for prediction of dMI in endometrial cancer patients....
E-cadherin and CD10 expression in atypical hyperplastic and malignant endometrial lesions
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Ahmed, A.R.H.; Muhammad, E.M.S.
2014-01-01
Background: Loss of E-cadherin is a critical step for development and progression of malignant tumors. CD10; a marker of non-neoplastic and neoplastic endometrial stroma, is associated with aggressiveness of many epithelial malignancies. Aims: To evaluate expression and correlation of E-cadherin and CD10 in endometrial lesions and their possible role in differentiating atypical endometrial hyperplasia from endometrial carcinoma. The association of E-cadherin and CD10 expression with clinico-pathological parameters of endometrial carcinoma was also investigated. Materials and methods: Fifty four cases including 28 endometrial carcinomas; 19 endometrial hyperplasia and 7 cases of normal endometrial changes were enrolled for this study. The expression of E-cadherin and CD10 was evaluated by immunohistochemistry using the streptavidin–biotin technique. Results: There was a strong association between malignant change of endometrial glands and membrano- cytoplasmic localization of E-cadherin (p< 0.001). Expression of E-cadherin but not CD10 was significantly higher in endometrial carcinomas compared to atypical endometrial hyperplasia (p < 0.01). Expression of E-cadherin was not associated with CD10 expression in different endometrial lesions. High grade tumors expressed low levels of both E-cadherin (p<0.01) and CD10 (p < 0.05) and serous endometrial carcinoma had low E-cadherin and CD10 expression compared to endometrioid carcinoma (p< 0.01 and <0.05, respectively). Expression of both molecules showed no association with depth of tumor invasion or FIGO stage. Tumors with lower E-cadherin or CD10 expression had higher rates of vascular tumor emboli (p< 0.01 and <0.07, respectively). Conclusions: Although expression of E-cadherin and CD10 in endometrial lesions was not correlated, reduced expression of both molecules could be critical for progression of endometrial carcinoma.
[Surgical treatment of precancer and cancer of endometrium].
Ivanov, S; Khadzhiolov, N; Batashki, I
2007-01-01
Our aim was to evaluate occult presence of endometrial cancer in patients with atypical glandular hiperplasia and to compare the histological prognostic factors according to the status of the lymph nodes and the grading of the occult tumour. 306 patients were evaluated retrospectvely for the period of 1990-2007. They were operated one month after the hostological diagnostic atypical glandular hiperplasia obtained by D&C. All patients were with vaginal bleeding. The patients who had concomitant presence of endometrial hyperplasia and endometrial cancer were excluded from the study. One hundred patients (group A) with atypical glandular hyperplasia were compared with 206 patients (group B) without atypical glandular hyperplasia obtained by D&C. Mann and Witney test and chi-square test were used for statistical evaluation.. There was no difference between the age and the menopausal status in the two groups, only there was higher parity in group B. In group A patients with atypical glandular hyperlasia we found in 50% endometrial cancer intraoperatively, in 40% endometrial hyperplasia and in 10% normal endometrium. In the second group B were included the patients without atypical hyperplasia from D&C. In group B were found in 6% endometrial cancer in 44% endometrial hyperplasia and in 50% normal endometrium. In 30 patients was performed complete surgical staging. Six patients were with metastatic lymph nodes. All of them were with grading 2 (4 patients) and grading 3 (2 patients), and also with infiltration in the lymph-vascular spaces. Four patients were with nonendometrioid tumours (type 2 endometrial cancer). The careful preoperative and intraoperative evaluation of the endometrium is very important in patients with atypical glandular hyperplasia. It is reasonable to use frozen section in the time of hysterectomy for patients with atypical glandular hyperplasia. If tumour with grading 2/3 nonendometrioid cancer with lymph-vascular space invasion, is found
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Fujii, Shinya; Kido, Aki; Baba, Tsukasa; Fujimoto, Koji; Daido, Sayaka; Matsumura, Noriomi; Konishi, Ikuo; Togashi, Kaori
2015-01-01
Highlights: •We have assessed the peritumoral enhancement (PTE), which mimics SEE on DCE. •We evaluated the diagnostic accuracy of SEE for the myometrial invasion and the frequency of PTE. •We assessed the relationship between these enhancements and important pathologic factors. •PTE Type 1 is the main factor causing the overestimation of myometrial invasion using SEE on DCE. •PTE Type 2 correlates the myometrial invasion and may play an important role in the diagnosis of LVSI. -- Abstract: Objectives: To evaluate the diagnostic accuracy of subendometrial enhancement (SEE) in assessing the myometrial invasion in endometrial cancer, the frequency and clinical significance of peritumoral enhancement (PTE) on dynamic contrast enhanced (DCE) imaging. Materials and methods: MR images of 147 patients with endometrial cancer were retrospectively analyzed for intact SEE and PTEs: Type 1, a focal early enhancement peritumorally, and Type 2, an irregular thin-layered early intense enhancement peritumorally. Two radiologists independently assessed intact SEE and PTEs on DCE imaging and compared the lesions by the presence and depth of myometrial invasion, grade, lymphovascular space involvement (LVSI), and lymph node metastasis. The relationship between SEE, PTEs, and each factor was analyzed using univariate and multivariate analyses. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy were calculated for SEE. Results: The sensitivity, specificity, PPV, NPV and diagnostic accuracy for myometrial invasion based on SEE disruption on DCE were 96.6%, 32.1–46.4%, 85.8–88.5%, 69.2–76.5%, and 84.4–87.1%. According to multivariate analysis, SEE significantly predicted myometrial invasion (p < 0.0001). PTE Type 2 significantly predicted myometrial invasion presence (p < 0.05) and depth (p < 0.01). Conclusion: Diagnosis of myometrial invasion only by using SEE might be difficult on DCE-MRI due to the
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Fujii, Shinya [Division of Radiology, Department of Pathophysiological and Therapeutic Science, Faculty of Medicine, Tottori University, Yonago (Japan); Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, Kyoto (Japan); Kido, Aki, E-mail: akikido@kuhp.kyoto-u.ac.jp [Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, Kyoto (Japan); Baba, Tsukasa [Departments of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, Kyoto (Japan); Fujimoto, Koji; Daido, Sayaka [Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, Kyoto (Japan); Matsumura, Noriomi; Konishi, Ikuo [Departments of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, Kyoto (Japan); Togashi, Kaori [Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, Kyoto (Japan)
2015-04-15
Highlights: •We have assessed the peritumoral enhancement (PTE), which mimics SEE on DCE. •We evaluated the diagnostic accuracy of SEE for the myometrial invasion and the frequency of PTE. •We assessed the relationship between these enhancements and important pathologic factors. •PTE Type 1 is the main factor causing the overestimation of myometrial invasion using SEE on DCE. •PTE Type 2 correlates the myometrial invasion and may play an important role in the diagnosis of LVSI. -- Abstract: Objectives: To evaluate the diagnostic accuracy of subendometrial enhancement (SEE) in assessing the myometrial invasion in endometrial cancer, the frequency and clinical significance of peritumoral enhancement (PTE) on dynamic contrast enhanced (DCE) imaging. Materials and methods: MR images of 147 patients with endometrial cancer were retrospectively analyzed for intact SEE and PTEs: Type 1, a focal early enhancement peritumorally, and Type 2, an irregular thin-layered early intense enhancement peritumorally. Two radiologists independently assessed intact SEE and PTEs on DCE imaging and compared the lesions by the presence and depth of myometrial invasion, grade, lymphovascular space involvement (LVSI), and lymph node metastasis. The relationship between SEE, PTEs, and each factor was analyzed using univariate and multivariate analyses. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy were calculated for SEE. Results: The sensitivity, specificity, PPV, NPV and diagnostic accuracy for myometrial invasion based on SEE disruption on DCE were 96.6%, 32.1–46.4%, 85.8–88.5%, 69.2–76.5%, and 84.4–87.1%. According to multivariate analysis, SEE significantly predicted myometrial invasion (p < 0.0001). PTE Type 2 significantly predicted myometrial invasion presence (p < 0.05) and depth (p < 0.01). Conclusion: Diagnosis of myometrial invasion only by using SEE might be difficult on DCE-MRI due to the
The Retrograde and Retroperitoneal Totally Laparoscopic Hysterectomy for Endometrial Cancer
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Eugenio Volpi
2012-01-01
Full Text Available Introduction. We retrospectively report our experience with the utilization of an original procedure for total laparoscopic hysterectomy based on completely retrograde and retroperitoneal technique for surgical staging and treatment of the endometrial cancer. The surgical, financial, and oncological advantages are here discussed. Methods. The technique used here has been based on a combination of a retroperitoneal approach with a retrograde and lateral dissection of the bladder and retrograde culdotomy with variable resection of parametrium. No disposable instruments and no uterine manipulator were utilized. Results. Intraoperative and postoperative complications were observed in 10% of the cases overall. Operative time length and mean haemoglobin drop value results were 129 min and 125 mL, respectively. Most patients were dismissed on days 3–5 from the hospital. Seventy-eight percent of the patients were alive with no evidence of disease at mean followup of 49 months. Conclusions. Our original laparoscopic technique is based on a retroperitoneal approach in order to rapidly control main uterine vessels coagulation, constantly check the ureter, and eventually decide type and site of lymph nodes removal. This procedure has important cost saving implications and the avoidance of uterine manipulator is of matter in case such as these of uterine malignancy.
High-dose-rate brachytherapy alone post-hysterectomy for endometrial cancer
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MacLeod, Craig; Fowler, Allan; Duval, Peter; D'Costa, Ieta; Dalrymple, Chris; Firth, Ian; Elliott, Peter; Atkinson, Ken; Carter, Jonathan
1998-01-01
Purpose: To evaluate the outcome of post-hysterectomy adjuvant vaginal high-dose-rate (HDR) brachytherapy. Methods and Materials: A retrospective analysis was performed on a series of 143 patients with endometrial cancer treated with HDR brachytherapy alone post-hysterectomy from 1985 to June 1993. Of these patients, 141 received 34 Gy in four fractions prescribed to the vaginal mucosa in a 2-week period. The median follow-up was 6.9 years. Patients were analyzed for treatment parameters, survival, local recurrence, distant relapse, and toxicity. Results: Five-year relapse free survival and overall survival was 100% and 88% for Stage 1A, 98% and 94% for Stage IB, 100% and 86% for Stage IC, and 92% and 92% for Stage IIA. The overall vaginal recurrence rate was 1.4%. The overall late-toxicity rate was low, and no RTOG grade 3, 4, or 5 complications were recorded. Conclusion: These results are similar to reported international series that have used either low-dose-rate or HDR brachytherapy. The biological effective dose was low for both acute and late responding tissues compared with some of the HDR brachytherapy series, and supports using this lower dose and possibly decreasing late side-effects with no apparent increased risk of vaginal recurrence