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Sample records for borderline ovarian tumors

  1. Hormone therapy and ovarian borderline tumors

    DEFF Research Database (Denmark)

    Mørch, Lina Steinrud; Løkkegaard, Ellen; Andreasen, Anne Helms

    2012-01-01

    Little is known about the influence of postmenopausal hormone therapy on the risk of ovarian borderline tumors. We aimed at assessing the influence of different hormone therapies on this risk.......Little is known about the influence of postmenopausal hormone therapy on the risk of ovarian borderline tumors. We aimed at assessing the influence of different hormone therapies on this risk....

  2. [Laparoscopic management of ovarian borderline tumors].

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    Cortés Algara, A; Charles, L; González Ramírez, P; Río de la Loza, F; Aranda Flores, C E

    2001-09-01

    The objective of this communication is to present a patient case with ovarian borderline tumor. The conservative management for laparoscopy, and we performed an analysis of the mundial literature in which respect to the conservative and laparoscopy management, in spite of the laparoscopy management are of controversy.

  3. Risk of borderline ovarian tumors among women with benign ovarian tumors

    DEFF Research Database (Denmark)

    Guleria, Sonia; Jensen, Allan; Kjær, Susanne K

    2018-01-01

    OBJECTIVE: A growing number of studies suggest that some ovarian cancers can arise from benign and borderline ovarian tumors. However, studies on the association between benign and borderline ovarian tumors are lacking. We studied the overall- and histotype-specific risk of borderline ovarian...... tumors among women with a benign ovarian tumor. METHODS: This nationwide cohort study included all Danish women diagnosed with a benign ovarian tumor (n=139,466) during 1978-2012. The cohort was linked to the Danish Pathology Data Bank and standardized incidence ratios (SIR) with 95% confidence intervals...... (CI) were calculated. RESULTS: Women with benign ovarian tumors had increased risks for subsequent borderline ovarian tumors (SIR 1.62, 95% CI 1.43-1.82), and this applied to both serous (SIR 1.69, 95% CI 1.39-2.03) and mucinous (SIR 1.75, 95% CI 1.45-2.10) histotypes of borderline ovarian tumors...

  4. Risk of borderline ovarian tumors among women with benign ovarian tumors: A cohort study.

    Science.gov (United States)

    Guleria, Sonia; Jensen, Allan; Kjær, Susanne K

    2018-01-01

    A growing number of studies suggest that some ovarian cancers can arise from benign and borderline ovarian tumors. However, studies on the association between benign and borderline ovarian tumors are lacking. We studied the overall- and histotype-specific risk of borderline ovarian tumors among women with a benign ovarian tumor. This nationwide cohort study included all Danish women diagnosed with a benign ovarian tumor (n=139,466) during 1978-2012. The cohort was linked to the Danish Pathology Data Bank and standardized incidence ratios (SIR) with 95% confidence intervals (CI) were calculated. Women with benign ovarian tumors had increased risks for subsequent borderline ovarian tumors (SIR 1.62, 95% CI 1.43-1.82), and this applied to both serous (SIR 1.69, 95% CI 1.39-2.03) and mucinous (SIR 1.75, 95% CI 1.45-2.10) histotypes of borderline ovarian tumors. The risk for borderline ovarian tumors was primarily increased for women diagnosed with a benign ovarian tumor before 40years of age. The risk remained increased up to 9years after a benign ovarian tumor diagnosis. Finally, the associations did not change markedly when analyzed for the different histotypes of benign (solid and cystic tumors) and borderline (serous and mucinous tumors) ovarian tumors. Women with benign ovarian tumors have a long-term increased risk for borderline ovarian tumors. However, as all associations in this study were only adjusted for age and calendar period of diagnosis, more studies that are able to adjust for additional potential confounding variables are required to further understand these associations. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Lead, selenium and nickel concentrations in epithelial ovarian cancer, borderline ovarian tumor and healthy ovarian tissues.

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    Canaz, Emel; Kilinc, Metin; Sayar, Hamide; Kiran, Gurkan; Ozyurek, Eser

    2017-09-01

    Wide variation exists in ovarian cancer incidence rates suggesting the importance of environmental factors. Due to increasing environmental pollution, trace elements and heavy metals have drawn attention in studies defining the etiology of cancer, but scant data is available for ovarian cancer. Our aim was to compare the tissue concentrations of lead, selenium and nickel in epithelial ovarian cancer, borderline tumor and healthy ovarian tissues. The levels of lead, selenium and nickel were estimated using atomic absorption spectrophotometry in formalin-fixed paraffin-embedded tissue samples. Tests were carried out in 20 malignant epithelial ovarian cancer, 15 epithelial borderline tumor and 20 non-neoplastic healthy ovaries. Two samples were collected for borderline tumors, one from papillary projection and one from the smooth surface of cyst wall. Pb and Ni concentrations were found to be higher both in malignant and borderline tissues than those in healthy ovaries. Concentrations of Pb and Ni in malignant tissues, borderline papillary projections and capsular tissue samples were not different. Comparison of Se concentrations of malignant, borderline and healthy ovarian tissues did not reveal statistical difference. Studied metal levels were not found to be different in either papillary projection or in cyst wall of the borderline tumors. This study revealed the accumulation of lead and nickel in ovarian tissue is associated with borderline and malignant proliferation of the surface epithelium. Accumulation of these metals in epithelial ovarian cancer and borderline ovarian tumor has not been demonstrated before. Copyright © 2017 Elsevier GmbH. All rights reserved.

  6. Diagnosis, Treatment, and Follow-Up of Borderline Ovarian Tumors

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    Zikan, Michal; Dundr, Pavel; Cibula, David

    2012-01-01

    Borderline ovarian tumors represent a heterogeneous group of noninvasive tumors of uncertain malignant potential with characteristic histology. They occur in younger women, are present at an early stage, and have a favorable prognosis, but symptomatic recurrence and death may be found as long as 20 years after therapy in some patients. The molecular changes in borderline ovarian tumors indicate linkage of this disease to type I ovarian tumors (low-grade ovarian carcinomas). The pathological stage of disease and subclassification of extraovarian disease into invasive and noninvasive implants, together with the presence of postoperative macroscopic residual disease, appear to be the major predictor of recurrence and survival. However, it should be emphasized that the most important negative prognostic factor for recurrence is just the use of conservative surgery, but without any impact on patient survival because most recurrent diseases are of the borderline type—easily curable and with an excellent prognosis. Borderline tumors are difficult masses to correctly preoperatively diagnose using imaging methods because their macroscopic features may overlap with invasive and benign ovarian tumors. Over the past several decades, surgical therapy has shifted from a radical approach to more conservative treatment; however, oncologic safety must always be balanced. Follow-up is essential using routine ultrasound imaging, with special attention paid to the remaining ovary in conservatively treated patients. Current literature on this topic leads to a number of controversies that will be discussed thoroughly in this article, with the aim to provide recommendations for the clinical management of these patients. PMID:23024155

  7. Epithelial borderline ovarian tumor: Diagnosis and treatment strategy.

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    Ushijima, Kimio; Kawano, Kouichiro; Tsuda, Naotake; Nishio, Shin; Terada, Atsumu; Kato, Hiroyuki; Tasaki, Kazuto; Matsukuma, Ken

    2015-05-01

    Epithelial borderline ovarian tumors (BOT) are distinctive from benign tumors and carcinoma. They occur in younger women more often than carcinoma, and there is some difficulty making correct diagnosis of BOT. Two subtypes of BOT, serous and mucinous borderline tumor have different characteristics and very different clinical behavior. Serous borderline tumor (SBT) with micropapillary pattern shows more incidence of extra ovarian disease and often coexists with invasive implant. SBT with micropapillary pattern in advanced stage has showed a worse prognosis than typical SBT. Huge mucinous borderline tumors have histologic heterogeneity, and the accuracy of frozen section diagnosis is relatively low. Extensive sampling is required to reach a correct pathological diagnosis. Mucinous adenoma (intestinal type) also runs the risk of recurrence after cystectomy, or intraoperative rupture of cyst. Laparoscopic procedure for BOT has not increased the risk of recurrence. Fertility preserving procedures are generally accepted, except in advanced stage SBT with invasive implants. Only cystectomy shows a significant risk of recurrence. Re-staging surgery and full staging surgery is not necessary for all BOT. We should not attempt to treat them uniformly, by the single diagnosis of "borderline tumor". It depends on histologic type. Close communication with the pathologist is necessary to gain more detail and ask more pathological samples in order to make the optimal treatment strategy for each individual patients.

  8. Pelvic Inflammatory Disease and the Risk of Ovarian Cancer and Borderline Ovarian Tumors

    DEFF Research Database (Denmark)

    Rasmussen, Christina B; Kjaer, Susanne K; Albieri, Vanna

    2017-01-01

    Inflammation has been implicated in ovarian carcinogenesis. However, studies investigating the association between pelvic inflammatory disease (PID) and ovarian cancer risk are few and inconsistent. We investigated the association between PID and the risk of epithelial ovarian cancer according...... to tumor behavior and histotype. We pooled data from 13 case-control studies, conducted between 1989 and 2009, from the Ovarian Cancer Association Consortium (OCAC), including 9,162 women with ovarian cancers, 2,354 women with borderline tumors, and 14,736 control participants. Study-specific odds ratios...... were estimated and subsequently combined into a pooled odds ratio using a random-effects model. A history of PID was associated with an increased risk of borderline tumors (pooled odds ratio (pOR) = 1.32, 95% confidence interval (CI): 1.10, 1.58). Women with at least 2 episodes of PID had a 2-fold...

  9. Long-term survival in women with borderline ovarian tumors: a population-based survey of borderline ovarian tumors in Sweden 1960-2007.

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    Kalapotharakos, Grigorios; Högberg, Thomas; Bergfeldt, Kjell; Borgfeldt, Christer

    2016-04-01

    We conducted an evaluation of incidence and survival of women with borderline ovarian tumors in Sweden. All women diagnosed with borderline ovarian tumor in the Swedish Cancer Register 1960-2007 (n = 6252) combined with follow up in the Swedish Death Registry to 1 July 2009 were included. Estimation of age-standardized relative survival rate according to time periods for diagnosis. The incidence of borderline ovarian tumors increased during the study period, with a steep increase during the 1980s. The age standardized 5-year relative survival including all borderline tumors diagnosed 2000-07 was 97% (95% CI 92-99%). In women aged ≤64 years, the 10-year relative survival related to age at diagnosis of borderline tumors ranged from 95 to 98% and was 89% in women aged 65-74 years. In a multivariable analysis including age and decade of diagnosis relative survival for every decade increased. The 10-year relative survival in women with mucinous and serous borderline tumors did not differ significantly (p = 0.121). Results of the present study are reassuring about long-term survival in women with borderline ovarian tumors. The age-standardized relative survival rate increased across time periods for diagnosis. There was no difference in long-term survival between mucinous and serous borderline ovarian tumors. © 2016 Nordic Federation of Societies of Obstetrics and Gynecology.

  10. Tubal ligation and salpingectomy and the risk of epithelial ovarian cancer and borderline ovarian tumors

    DEFF Research Database (Denmark)

    Madsen, C; Baandrup, Louise; Dehlendorff, Christian

    2015-01-01

    OBJECTIVE: According to the recent theories on the ovarian cancer origin, any protective effect of tubal ligation may vary with histologic subtype of ovarian cancer. Furthermore, bilateral salpingectomy may represent an opportunity for surgical prevention of serous ovarian cancer. DESIGN: Nationw......OBJECTIVE: According to the recent theories on the ovarian cancer origin, any protective effect of tubal ligation may vary with histologic subtype of ovarian cancer. Furthermore, bilateral salpingectomy may represent an opportunity for surgical prevention of serous ovarian cancer. DESIGN...... ovarian cancer and borderline ovarian tumors stratified according to histology. RESULTS: Tubal ligation reduced overall epithelial ovarian cancer risk (odds ratios 0.87; 95% confidence interval 0.78-0.98). We observed significant risk variation according to histology (p = 0.003) with the strongest risk...... reductions associated with endometrioid cancer (odds ratios 0.66; 95% confidence interval 0.47-0.93) and epithelial ovarian cancer of "other" histology (odds ratios 0.60; 95% confidence interval 0.43-0.83). Tubal ligation was not associated with risk of borderline ovarian tumors. Finally, bilateral...

  11. Trends in incidence of borderline ovarian tumors in Denmark 1978-2006

    DEFF Research Database (Denmark)

    Hannibal, Charlotte Gerd; Huusom, Lene Drasbek; Kjaerbye-Thygesen, Anette

    2011-01-01

    To examine period-, age- and histology-specific trends in the incidence rate of borderline ovarian tumors in Denmark in 1978-2006.......To examine period-, age- and histology-specific trends in the incidence rate of borderline ovarian tumors in Denmark in 1978-2006....

  12. Mucinous borderline ovarian tumor: a case report with diagnostic insights on ultrasound findings

    Directory of Open Access Journals (Sweden)

    Anna Szymańska-Dubowik

    2016-12-01

    Full Text Available Borderline ovarian tumors represent about 10% of all epithelial ovarian cancers, but in contrast to epithelial ovarian cancers, they constitute a group of tumors with a much better prognosis. An assessment of clinical presentation, physical examination, radiological and biochemical findings is necessary to tailor management strategies for patients with ovarian tumors. The article, which is based on a case report, describes different approaches for preoperative diagnosis as well as discusses approaches that might bring some insights on tumor histology. Furthermore, it raises a question about which imaging techniques should be proposed for a reliable diagnosis of borderline ovarian tumors to ensure safe surgery planning.

  13. Pelvic inflammatory disease and risk of invasive ovarian cancer and ovarian borderline tumors

    DEFF Research Database (Denmark)

    Rasmussen, Christina B; Faber, Mette T; Jensen, Allan

    2013-01-01

    PURPOSE: The aim of the study was to examine the potential association between a history of pelvic inflammatory disease (PID) and risk of epithelial ovarian cancer or ovarian borderline tumors. METHODS: In a population-based case-control study in Denmark, we included 554 women with invasive ovarian...... cancer, 202 with ovarian borderline tumors, and 1,564 controls aged 35-79 years. The analyses were performed in multiple logistic regression models. RESULTS: We found a significantly increased risk of ovarian borderline tumors among women with a history of PID (OR = 1.50; 95% CI 1.......08-2.08) but no apparent association between PID and risk of invasive ovarian cancer (OR = 0.83; 95% CI 0.65-1.05). We found no effect of age at time of first PID or time since first PID on the risk for either condition. CONCLUSION: Our results suggest that a history of PID is associated with an increased risk of ovarian...

  14. Coffee, tea, and caffeine consumption and risk of epithelial ovarian cancer and borderline ovarian tumors

    DEFF Research Database (Denmark)

    Gosvig, Camilla F; Kjaer, Susanne K; Blaakær, Jan

    2015-01-01

    BACKGROUND: Epidemiological studies that have investigated the association between coffee, tea and caffeine consumption and ovarian cancer risk have produced conflicting results. Furthermore, only few studies have examined the role of coffee and tea consumption separately for borderline ovarian...... tumors. By use of data from a large Danish population-based case-control study, we examined the risk of ovarian tumors associated with coffee, tea, and caffeine consumption with a particular focus on characterizing risks by tumor behavior and histology. MATERIAL AND METHODS: From 1995 through 1999, we....... RESULTS: Both coffee (OR = 0.90; 95% CI 0.84-0.97 per cup/day) and total caffeine consumption from coffee and tea combined (OR = 0.93; 95% CI 0.88-0.98 per 100 mg/day) decreased the risk of ovarian cancer. These associations were significant only for the serous and "other" subtypes of ovarian cancer...

  15. Clinicopathologic features of ovarian neoplasms with emphasis on borderline ovarian tumors: an institutional perspective.

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    Hashmi, Atif Ali; Hussain, Zubaida Fida; Bhagwani, Aneel Roy; Edhi, Muhammad Muzzammil; Faridi, Naveen; Hussain, Syed Danish; Khan, Mehmood

    2016-04-06

    Ovarian cancer is the most lethal gynecologic malignancy and it represents third most common malignancy in Karachi (after breast and oral cancer). Due to lack of well established cancer registry in our country, changing trends of ovarian tumors has not been determined. Therefore we aimed to establish the current trends and classification of ovarian tumors in our setup according to latest WHO guidelines. We retrospectively analyzed 162 cases of ovarian tumors that underwent surgical resection from January 2009 till December 2014. Specimens were received in histopathology department, Liaquat National hospital and cases were examined by senior histopathologists and classified according to latest WHO guidelines. Various histopathologic parameters including capsular invasion, omental and lymph node meatstasis along with uterine and fallopian tube involvement were determined apart from tumor type and grade. Mean age at diagnosis was 35.8 years (± 15.5). surface epithelial tumors were most common, 109 cases (67.2%) followed by germ cell tumors, 44 cases (27.1%) and sex cord stromal tumors, 8 cases (4.9%). Serous tumors were most common surface epithelial tumors with 90% benign morphology. On the other hand, mucinous tumors showed a higher percentage of borderline and malignant features (16.7 and 14.6% respectively). Higher incidence of capsular invasion and omental metastasis was noted in endometroid and serous carcinoma compared to mucinous tumors. We noted a higher frequency of young age ovarian cancers in our set up. Serous and endometroid carcinomas were found to be associated with adverse prognostic factors like capsular invasion and omental metastasis. Moreover a significantly higher proportion of ovarian tumors constitute mucinous histology including borderline tumors. Whether this represents a changing trend towards biology of these tumors in this part of the world needs to be uncovered by further studies.

  16. Validation of epithelial ovarian cancer and fallopian tube cancer and ovarian borderline tumor data in the Danish Gynecological Cancer Database

    DEFF Research Database (Denmark)

    Petri, A.L.; Kjaer, S.K.; Christensen, I.J.

    2009-01-01

    OBJECTIVE: To validate the data on epithelial ovarian cancer, fallopian tube cancer and borderline ovarian tumors registered in the nationwide Danish Gynecological Cancer Database (DGCD) in 2005 and 2006. The DGCD is a multidisciplinary database that contains data for research and quality...... improvement. DESIGN: Comparative registry-based study supplemented with data from medical records. SETTING: Six hospitals in Denmark. PARTICIPANTS: Women registered with epithelial ovarian cancer, fallopian tube cancer and borderline ovarian tumor. MAIN OUTCOME MEASURE: Data completeness and strength......: The validity of ovarian cancer data in the DGCD is sufficient for quality monitoring in gynecological oncology Udgivelsesdato: 2009...

  17. Increased risk of borderline ovarian tumors in women with a history of pelvic inflammatory disease

    DEFF Research Database (Denmark)

    Rasmussen, Christina B; Jensen, Allan; Albieri, Vanna

    2016-01-01

    Objective Some studies suggest that pelvic inflammatory disease (PID) is a potential risk factor for ovarian cancer. However, only few studies have investigated the association between PID and risk of borderline ovarian tumors. We conducted a population-based cohort study to investigate...... the association between PID and risk of borderline ovarian tumors. Methods Using various nationwide Danish registries we identified all women in Denmark during 1978–2012, who were born during 1940–1970 (n = 1,318,925). Of these, 81,263 women were diagnosed with PID in the study period, and 2736 women had...... a borderline ovarian tumor (1290 serous and 1344 mucinous). Hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between PID and risk of borderline tumors were estimated using Cox regression models with adjustment for potential confounders. Results A history of PID was associated...

  18. Differentiating between borderline and invasive malignancies in ovarian tumors using a multivariate logistic regression model

    Directory of Open Access Journals (Sweden)

    Jiabin Chen

    2015-08-01

    Conclusion: Differentiation between borderline and invasive ovarian tumors can be achieved using a model based on the following criteria: menopausal status; cancer antigen 125 level; and ultrasound parameters. The model is helpful to oncologists and patients in the initial evaluation phase of ovarian tumors.

  19. Increased risk of second cancer among patients with ovarian borderline tumors.

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    Bouchardy, Christine; Fernandez, Sarah; Merglen, Arnaud; Usel, Massimo; Fioretta, Gérald; Rapiti, Elisabetta; Schubert, Hyma; Pelte, Marie-Françoise; Chappuis, Pierre O; Vlastos, Georges

    2008-05-01

    Several studies have demonstrated a higher risk of colorectal and breast cancers subsequent to invasive ovarian cancer. Such risk has not been investigated for ovarian borderline tumors. We aim to evaluate the risk of subsequent cancer occurrence among patients with borderline ovarian tumors in a population-based setting. We identified 171 patients with a diagnosis of borderline ovarian tumors recorded at the Geneva Cancer Registry, Switzerland. We calculated age and period standardized incidence ratios (SIR) of second tumor occurrence by dividing the number of observed cases by the number of expected cases in the cohort, using cancer incidence rates of the general female population. The risk of developing second cancer was 1.85-fold (95% Confidence Interval [CI]: 1.10-2.92, n=16) higher among women with borderline ovarian tumors compared to that expected in the general population. The excess of risk primarily concerned colorectal cancer (SIR: 3.97, CI: 1.38-12.95, n=5) and breast cancer (SIR: 2.09, CI: 0.84-4.31, n=7), but the latter result was not statistically significant (p=0.09). The increased risk of developing second cancer was mainly observed among patients diagnosed with ovarian borderline tumors occurring before the age of 50. These results were not explained by surveillance bias or by metastasis from one site to another. Women with ovarian borderline tumors have an increased risk of developing secondary cancer, particularly colorectal cancer. These results point to potential common risk factors for these tumors and ask for close surveillance of patients with borderline ovarian tumors.

  20. Mitochondrial DNA sequencing demonstrates clonality of peritoneal implants of borderline ovarian tumors.

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    Girolimetti, Giulia; De Iaco, Pierandrea; Procaccini, Martina; Panzacchi, Riccardo; Kurelac, Ivana; Amato, Laura Benedetta; Dondi, Giulia; Caprara, Giacomo; Ceccarelli, Claudio; Santini, Donatella; Porcelli, Anna Maria; Perrone, Anna Myriam; Gasparre, Giuseppe

    2017-02-27

    Borderline ovarian tumors are rare low malignant potential neoplasms characterized by the absence of stromal invasion, whose main prognostic factors are stage and type of peritoneal implants. The latter are defined as invasive when cell proliferation invades the underlying tissue (peritoneal surface, omentum and intestinal wall), or noninvasive. It is still unknown if these implants are metastatic spread from the primary ovarian mass or a neoplastic transformation de novo of the peritoneal surface. Mitochondrial DNA sequencing was performed to assess clonality in eight patients presenting both borderline ovarian tumors and implants. In 37.5% of the cases, the same mitochondrial DNA mutation was present in both borderline ovarian tumors and the peritoneal implant, being this evidence that implants may arise as a consequence of a spread from a single ovarian site.

  1. Validation of epithelial ovarian cancer and fallopian tube cancer and ovarian borderline tumor data in the Danish Gynecological Cancer Database

    DEFF Research Database (Denmark)

    Petri, Anette Lykke; Kjaer, Susanne Krüger; Christensen, Ib J

    2009-01-01

    OBJECTIVE: To validate the data on epithelial ovarian cancer, fallopian tube cancer and borderline ovarian tumors registered in the nationwide Danish Gynecological Cancer Database (DGCD) in 2005 and 2006. The DGCD is a multidisciplinary database that contains data for research and quality improve...

  2. Safety of ovarian tissue transplantation in patients with borderline ovarian tumors.

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    Masciangelo, Rossella; Bosisio, Chiara; Donnez, Jacques; Amorim, Christiani A; Dolmans, Marie-Madeleine

    2018-02-01

    Is transplantation of cryopreserved ovarian tissue from patients with borderline ovarian tumors (BOTs) a safe procedure? BOT cells were found in frozen-thawed and xenografted ovarian tissue in 1 of 11 BOT patients. The risk of reintroducing malignant cells upon ovarian tissue transplantation has been subject of debate for many years. Reimplantation of cryopreserved ovarian tissue from leukemia patients is unsafe, while results from studies of cryopreserved ovarian tissue from other forms of cancer, such as Hodgkin's lymphoma, are reassuring. Prospective experimental study conducted in an academic research unit using ovarian tissue from 11 patients undergoing cryopreservation for BOTs. Histology, immunohistochemistry (IHC) for mucin 1 (MUC1) and cytokeratin 7 (CK7) and molecular analysis by reverse transcription quantitative polymerase chain reaction (RT-qPCR) for CK7 and MUC1 were performed on frozen-thawed ovarian tissue from 11 patients. Long-term (5 months) xenografting of ovarian tissue in immunodeficient mice was performed. The xenografts were analyzed by histology, IHC and RT-qPCR, furthermore IHC for CD10, a marker of endometriosis, was performed on a selected sample. Analysis by histology, IHC and RT-qPCR indicated 10 of the ovarian tissue samples were negative. Analysis of the xenograft samples indicated nine were negative for malignant cells but in two xenografts glandular lesions were detected by histology. In these two xenografts, CK7 and MUC1 markers were demonstrated by IHC and CK7 expression also by RT-qPCR. A BOT was confirmed in the xenograft in which the original ovarian tissue was positive, while in the other case IHC demonstrated expression of endometriosis marker CD10. Cryopreserved ovarian fragments cannot be tested before transplantation, therefore the preimplantation analysis cannot guarantee that all cryopreserved fragments will be free of BOT cells. BOT cells can be found in cryopreserved ovarian tissue from BOT patients, therefore

  3. Primary mucinous borderline tumor of the vermiform appendix mimicking ovarian carcinoma; case report.

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    Baykal, C; Türkmen, I C; Hizli, F; Doğusoy, G B; Sertep, I; Dünder, I

    2012-01-01

    Primary adenocarcinoma of the vermiform appendix is a very rare entity. Borderline mucinous tumor of the appendix is a much more rare disease. We present a 71-year-old woman with primary mucinous borderline tumor of the vermiform appendix. She was misdiagnosed as an ovarian carcinoma patient and operated on by a gynecologic oncology team. Her frozen section analysis of an appendicial mass resulted as borderline tumor of appendix vermiformis, and right hemicolectomy, as is advised in invasive colon tumors, was not carried out. Borderline mucinous tumor of the appendix vermiformis should be kept in mind in patients who have pseudomyxoma peritonei during surgery. Tumoral resection may be the definitive therapy in these patients.

  4. Benign multicystic peritoneal mesothelioma mimicking recurrence of an ovarian borderline tumor: a case report

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    Takemoto Shuji

    2012-05-01

    Full Text Available Abstract Introduction Benign multicystic peritoneal mesothelioma is an extremely rare tumor that occurs mainly in women in their reproductive age. Its preoperative diagnosis and adequate treatment are quite difficult to attain. Case presentation Our patient was a 23-year-old Japanese woman who had a history of right oophorectomy and left ovarian cystectomy for an ovarian tumor at 20 years of age. The left ovarian tumor had been diagnosed on histology as a mucinous borderline tumor. Two years and nine months after the initial operation, multiple cysts were found in our patient. A laparotomy was performed and her uterus, left ovary, omentum and pelvic lymph nodes were removed due to suspicion of recurrence of the borderline tumor. A histological examination, however, revealed that the cysts were not a recurrence of the borderline tumor but rather benign multicystic peritoneal mesothelioma. There were no residual lesions and our patient was followed up with ultrasonography. She remains free from recurrence nine months after treatment. Conclusion We report a case of benign multicystic peritoneal mesothelioma mimicking recurrence of an ovarian borderline tumor. Benign multicystic peritoneal mesothelioma should be suspected when a multicystic lesion is present in the pelvis as in the case presented here, especially in patients with previous abdominal surgery.

  5. Five years single institution retrospective analysis of the borderline ovarian tumors

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    Ghanim Khatib

    2016-12-01

    Conclusion: Borderline ovarian tumors have a favorable prognosis and therefore, unilateral salpingo-oophorectomy can be suggested to be a safely treatment approach for patients who desire to protect their fertility. [Cukurova Med J 2016; 41(4.000: 653-657

  6. p14 expression differences in ovarian benign, borderline and malignant epithelial tumors.

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    Cabral, Vinicius Duarte; Cerski, Marcelle Reesink; Sa Brito, Ivana Trindade; Kliemann, Lucia Maria

    2016-10-22

    Abnormalities in tumor suppressors p14, p16 and p53 are reported in several human cancers. In ovarian epithelial carcinogenesis, p16 and p53 show higher immunohistochemical staining frequencies in malignant tumors and are associated with poor prognoses. p14 was only analyzed in carcinomas, with conflicting results. There are no reports on its expression in benign and borderline tumors. This study aims to determine p14, p16 and p53 expression frequencies in ovarian benign, borderline and malignant tumors and their associations with clinical parameters. A cross-sectional study utilizing immunohistochemistry was performed on paraffin-embedded ovarian epithelial tumor samples. Clinical data were collected from medical records. Fisher's exact test and the Bonferroni correction were performed for frequency associations. Survival comparisons utilized Kaplan-Meier and log rank testing. Associations were considered significant when p carcinomas, 75 % of borderline and 45.7 % of benign tumors (p = 0.000). p53 negative staining was associated with benign tumors (2.9 % positive) (p = 0.016) but no difference was observed between borderline (16.7 %) and malignant tumors (29.7 %) (p = 0.560). No associations were found between expression rates, disease-free survival times or clinical variables. Carcinoma subtypes showed no difference in expression. This is the first description of p14 expression in benign and borderline tumors. It remains stable in benign and borderline tumors, while carcinomas show a significant absence of staining. This may indicate that p14 abnormalities occur later in carcinogenesis. p16 and p53 frequencies increase from benign to borderline and malignant tumors, similarly to previous reports, possibly reflecting the accumulation of inactive mutant protein. The small sample size may have prevented statistically significant survival analyses and clinical correlations. Future studies should investigate genetic abnormalities in p14 coding

  7. Ovarian borderline tumors in the 2014 WHO classification: evolving concepts and diagnostic criteria.

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    Hauptmann, Steffen; Friedrich, Katrin; Redline, Raymond; Avril, Stefanie

    2017-02-01

    Borderline ovarian tumors (BOT) are uncommon but not rare epithelial ovarian neoplasms, intermediate between benign and malignant categories. Since BOT were first identified >40 years ago, they have inspired controversies disproportionate to their incidence. This review discusses diagnostic criteria for the histologic subtypes of BOT, highlighting areas of diagnostic challenges, ongoing controversies, and changes in terminology implemented by the recent 2014 WHO Classification of Tumours of the Female Genital Organs. Emerging knowledge supports the notion that subtypes of borderline ovarian tumors comprise distinct biologic, pathogenetic, and molecular entities, precluding a single unifying concept for BOT. Serous borderline tumors (SBT) share molecular and genetic alterations with low-grade serous carcinomas and can present at higher stages with peritoneal implants and/or lymph node involvement, which validates their borderline malignant potential. All other (non-serous) subtypes of BOT commonly present at stage I confined to the ovary(ies) and are associated with overall survival approaching that of the general population. An important change in the WHO 2014 classification is the new terminology of non-invasive implants associated with SBT, as any invasive foci (previously called "invasive implants") are now in line with their biological behavior considered peritoneal low-grade serous carcinoma (LGSC). The controversy regarding the terminology of non-serous borderline tumors, called by some pathologists "atypical proliferative tumor" in view of their largely benign behavior, has not been resolved. The concepts of intraepithelial carcinoma and microinvasion may evolve in further studies, as their presence appears to have no prognostic impact and is subject to considerable inter-observer variability.

  8. Serum CA 125, carcinoembryonic antigen, and CA 19-9 as tumor markers in borderline ovarian tumors

    NARCIS (Netherlands)

    Engelen, MJA; de Bruijn, HWA; Hollema, H; ten Koor, KA; Willemse, PHB; Aalders, JG; van der Zee, AGJ

    Objectives. The goals of this study were to analyze preoperative serum levels of CA 125, carcinoembryonic antigen (CEA), and CA 19-9 in patients with borderline ovarian tumors and to investigate if routine assessment of these markers in follow-up may lead to earlier detection of recurrence. Methods.

  9. The role of restaging borderline ovarian tumors: single institution experience and review of the literature.

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    Zapardiel, Ignacio; Rosenberg, Piergiorgio; Peiretti, Michele; Zanagnolo, Vanna; Sanguineti, Fabio; Aletti, Giovanni; Landoni, Fabio; Bocciolone, Luca; Colombo, Nicoletta; Maggioni, Angelo

    2010-11-01

    Borderline ovarian tumors (BOTs) are a histological category of epithelial ovarian tumors and 70% of them are early diagnosed (stage I). Since early stage is the most important prognostic factor, restaging procedure could be justified. This study aims to evaluate the role of restaging surgery in the management of patients with borderline ovarian tumors referred to our Institution after being incompletely surgically staged in other hospitals. We retrospectively reviewed the charts of patients with BOT who were referred to our centre to undergo restaging procedure. From December 1995 to May 2008, 186 patients were treated for BOT and 70 patients met the inclusion criteria. Data collected included patients' age, primary and re-staging surgery details, FIGO stage after first and second procedure, pathological findings, and follow-up data. FIGO stage after primary surgery was IA in 46 patients (68.6%), IB in 7 patients (10.4%), IC in 12 patients (17.9%, 6 due to ruptured cyst), IIA in 1 patient (1.4%), IIB in 1 patient (1.4%), III B in 2 patients (2.8%), and IIIC in 1 patient (1.4%). Among stage I patients (representing 97% of all patients), 12.3% (8 patients) were up-staged. The upstaging rate among serous tumors was 16.2%, and 4% among mucinous tumors. The mean follow-up time was 60.4 months from restaging surgery (SD 30.6 months). We observed 8 primary recurrences of the disease and 3 second recurrences. There were no differences in terms of overall survival between patients who were upstaged and those who were not. Restaging procedure does not seem to have a significant impact on the management of patients diagnosed with borderline ovarian tumors, especially in mucinous subtype and apparent FIGO stage higher than I. Copyright © 2010 Elsevier Inc. All rights reserved.

  10. DNA Cytometry and Nuclear Morphometry in Ovarian Benign, Borderline and Malignant Tumors

    Directory of Open Access Journals (Sweden)

    Amina A. Gamal el Din

    2015-10-01

    CONCLUSION: We suggest that DNA ploidy and nuclear area combined, may be adjuncts to histopathology; in ovarian serous and mucinous benign, borderline and malignant neoplasms; identifying the aggressive borderline tumours.

  11. Ultrasonographic diagnosis and longitudinal follow-up of recurrences after conservative surgery for borderline ovarian tumors.

    Science.gov (United States)

    Franchi, Dorella; Boveri, Sara; Radice, Davide; Portuesi, Rosalba; Zanagnolo, Vanna; Colombo, Nicoletta; Testa, Antonia Carla

    2016-12-01

    Borderline ovarian tumors are generally diagnosed in young women. Because of the young age of patients at first diagnosis and at recurrence, and given the good prognosis of borderline ovarian tumors, a conservative surgical approach in those women who wish to preserve their fertility is advised. In this scenario, transvaginal ultrasound examination plays a key role in the detection of borderline ovarian tumor recurrence, and in assessment of amount of normal functioning parenchyma remaining. To date, no data are available about the natural history of borderline ovarian tumor recurrence. The aim of the study was to determine growth rate of recurrent ovarian cysts by a scheduled follow-up by ultrasound examination, in women previously treated with fertility-sparing surgery due to borderline ovarian tumors. In this prospective observational study, we collected data from 34 patients previously treated with fertility-sparing surgery due to borderline ovarian tumors, who had a suspicious recurrent lesion. The patients underwent transvaginal ultrasonographic examination every 3 months, until the clinical setting recommended proceeding with surgery. According to cyst size at study entry, they were categorized into 3 groups: ≤10 mm, 10-20 mm, and >20 mm. Summary statistics for cyst size, growth rate, and the probability of remaining within the same dimension category at first ultrasound during the follow-up were also obtained. For each cyst the growth rate was calculated as the slope of the linear interpolation between 2 consecutive measurements. Follow-up timing (P 20 mm. The final histology of all recurrent lesions confirmed the same histotype of primary borderline ovarian tumors. This article represents the first observational study that describes the trend in the growth rate of borderline ovarian tumor recurrence in relation to their size detected at the first ultrasound examination. The findings of this study seem to confirm, in selected patients, that a thorough

  12. Bilateral Borderline Serous Ovarian Tumor Following Three Cycles of Clomiphene Treatment in 19 Years Old Subfertile Woman with Polycystic Ovaries: A Case Report

    Directory of Open Access Journals (Sweden)

    Orhan Gelişen

    2006-08-01

    We also review published case reports of borderline ovarian tumors following ovulation induction to update the medical literature about this rare yet serious condition may be encountered by physicians providing infertility treatment. A borderline ovarian neoplasm in polycystic ovaries should be considered if a patient develops unforeseen ovarian mass (es following ovulation induction.

  13. Malignant and borderline epithelial ovarian tumors in the pediatric and adolescent population.

    Science.gov (United States)

    Nasioudis, Dimitrios; Alevizakos, Michail; Holcomb, Kevin; Witkin, Steven S

    2017-02-01

    Malignant and borderline ovarian tumors of epithelial origin are rarely encountered among prepubertal girls and adolescents. The aim of this population-based study was to elucidate their clinicopathological characteristics and prognosis using a multi-institutional tumor registry. The National Cancer Institute's Surveillance, Epidemiology, and End Results database was accessed and a cohort of females aged ovarian tumor (BOT) or a malignant epithelial ovarian carcinoma (EOC) was accessed. Observed survival (OS) was assessed using the Kaplan-Meier method. Comparisons were made using the log-rank test. A total of 114 cases diagnosed with BOT between 1988 and 2000 were identified; 61/114 (53.5%) and 51/114 (44.8%) of BOT were of serous or mucinous histology respectively. Ten-year OS for those with BOT was 97.3%. A total of 140 cases of EOC were identified. Median age was 17 years and the most common histological subtypes were mucinous 79/140 (56.4%) and serous 29/140 (20.7%) adenocarcinoma. Most had stage I disease 92/131 (70.2%) and fertility-sparing surgery was commonly performed. Five-year OS for those with stage I disease was 93.6% compared to 48.3% for cases with exta-ovarian tumor spread (ptumors confined to the ovary. OS survival for those with stage I disease is excellent. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. A nationwide study of ovarian serous borderline tumors in Denmark 1978-2002

    DEFF Research Database (Denmark)

    Hannibal, Charlotte Gerd; Vang, Russell; Junge, Jette

    2017-01-01

    OBJECTIVE: Absolute risk and risk factors for recurrence and ovarian serous carcinoma following ovarian serous borderline tumors (SBTs) is not well-established. METHODS: We included all women with SBTs in Denmark, 1978-2002. Diagnoses were confirmed by centralized pathology review and classified...... as atypical proliferative serous tumor (APST) or noninvasive low-grade serous carcinoma (LGSC). Implants were classified as noninvasive or invasive. Medical records were collected and reviewed, and follow-up was obtained. Subsequent diagnoses were also confirmed by centralized pathology review. We examined...... absolute risk and risk factors for recurrent APST and serous carcinoma using Cox regression. RESULTS: The absolute serous carcinoma risk after, respectively, 5 and 20years was 5.0% and 13.9% for noninvasive LGSC, and 0.9% and 3.7% for APST. Serous carcinoma risk was significantly higher following...

  15. Parity, infertility, oral contraceptives, and hormone replacement therapy and the risk of ovarian serous borderline tumors

    DEFF Research Database (Denmark)

    Rasmussen, Emma L Kaderly; Hannibal, Charlotte Gerd; Dehlendorff, Christian

    2017-01-01

    OBJECTIVE: Few studies have examined the risk of an ovarian serous borderline tumor (SBT) associated with parity, infertility, oral contraceptives (OCs), or hormone replacement therapy (HRT), which was the study aim. METHODS: This nationwide case-control study included all women with an SBT...... or salpingo-oophorectomy were excluded. Conditional logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: We found a strongly decreased risk of SBTs among parous women which decreased with increasing number of children (p

  16. The Prognostic and Clinical Value of Morphometry and DNA Cytometry in Borderline Ovarian Tumors : A Prospective Study

    NARCIS (Netherlands)

    Verbruggen, Marjolijn B.; van Diest, Paul J.; Baak, Jan P.; Broeckaert, Mark A. M.; Kenemans, Peter; Verheijen, Rene H. M.

    To evaluate if morphometric features (mitotic activity index, volume percentage of epithelium, and DNA ploidy) are prognostic markers in borderline ovarian tumors (BOTs). Ninety-three serous and mucinous consecutive BOTs diagnosed between 1989 and 2002 were studied. In all tumors, mitotic activity

  17. Retrospective evaluation of borderline ovarian tumors: single center experience of 183 cases.

    Science.gov (United States)

    Gungor, Tayfun; Cetinkaya, Nilufer; Yalcin, Hakan; Ozdal, Bulent; Ozgu, Emre; Baser, Eralp; Uygur, Dilek; Caglar, Mete; Sirvan, Levent; Erkaya, Salim

    2015-01-01

    Borderline ovarian tumors (BOTs) constitute about a quarter of epithelial ovarian malignancies and require different treatment approaches. The present study aims to document the experience of a single center on the treatment outcome of women who had conservative or comprehensive surgery for BOTs. One hundred eighty-three patients with BOTs, diagnosed and/or treated in our center between January of 2000 and March of 2013, were reviewed retrospectively. The mean age at diagnosis was 40.6 years old (range 17-78). Ninety-five patients (51 %) were ≤40 years. Comprehensive surgical staging and fertility sparing surgery were performed in 49 % (n = 91) and 48 % of patients (n = 89) respectively. A hundred and forty-seven patients had stage IA disease (80 %). The most common type of BOT was serous in histology with 18 % bilateralism. CA-125 and CA-199 levels were increased in 29 (19 %) and 15 (10 %) patients with stage IA disease. Non-invasive tumor implants were diagnosed in 9 patients (4 %) and uterine involvement was 2 % among BOT patients that underwent hysterectomies. The mean post-operative follow-up period was 20.4 months (range 6-78 months). Disease recurrence was seen in 5 patients indicating overall recurrence rate of 2.7 %. In our study, we evaluated a large data pool of 183 patients diagnosed with borderline epithelial ovarian tumors. BOTs have a relatively better prognosis than invasive epithelial ovarian cancer. Surgery with proper staging is the cornerstone of treatment. Patients with BOTs at the early stage can undergo fertility sparing surgery with close follow-up.

  18. Tumor borderline do ovário localizado no canal inguinal: relato de caso A borderline ovarian tumor in inguinal canal: case report

    Directory of Open Access Journals (Sweden)

    Vinícius Basso Preti

    2010-06-01

    Full Text Available Os sintomas do tumor ovariano são inespecíficos e uma forma rara de apresentação é como conteúdo de uma hérnia inguinal. Relatamos o caso de uma paciente de 82 anos, com diagnóstico de câncer de mama e lesão anexial hipoecoica à ecografia. A mesma foi submetida à cirurgia conservadora da mama e à laparotomia, com achado de lesão ovariana sólido-cística no interior do canal inguinal à direita. A análise por congelação foi negativa para malignidade, e o exame anatomopatológico mostrou tratar-se de tumor ovariano borderline.The symptoms of ovarian tumor are not specific and a rare presentation of the tumor is as the content of an inguinal hernia. We reported a case of an 82-year-old woman, diagnosed with breast cancer and with a concomitant hypoecoic adnexal mass at the ecographic exam. The patient was treated with conservative breast surgery and laparotomy. A cystic-solid ovarian lesion was found inside the right inguinal canal. Frozen-section examination was negative for malignancy, and the anatomopathological analysis revealed a borderline ovarian tumor.

  19. DNA Cytometry and Nuclear Morphometry in Ovarian Benign, Borderline and Malignant Tumors.

    Science.gov (United States)

    El Din, Amina A Gamal; Badawi, Manal A; Aal, Shereen E Abdel; Ibrahim, Nihad A; Morsy, Fatma A; Shaffie, Nermeen M

    2015-12-15

    Ovarian carcinoma is a leading cause of death in gynecological malignancy. Ovarian surface epithelial serous and mucinous tumours are classified as benign, borderline, and malignant. The identification of borderline tumours most likely to act aggressively remains an important clinical issue. This work aimed to study DNA ploidy and nuclear area in ovarian serous and mucinous; benign, borderline and malignant tumours. This study included forty ovarian (23 serous and 17 mucinous) tumours. Paraffin blocks were sectioned; stained with haematoxylin and eosin for histopathologic and morphometric studies and with blue feulgen for DNA analysis. All four serous and six out of nine mucinous benign tumours were diploid. All eight serous and five mucinous malignant tumours were aneuploid. Nine of eleven (81.8%) serous and all three mucinous borderline tumours were aneuploid. There were highly significant differences in mean aneuploid cells percentage between serous benign (1.5%), borderline (45.6%) and malignant (74.5%) (p = 0.0001) and between mucinous benign (13.2%) and both borderline (63.7%) and malignant (68.4%) groups (p = 0.0001). There were significant differences in nuclear area between serous benign (26.191%), borderline (45.619%) and malignant (67.634 %) and a significant positive correlation between mean percentage aneuploid value and mean nuclear area in all serous and mucinous groups. We suggest that DNA ploidy and nuclear area combined, may be adjuncts to histopathology; in ovarian serous and mucinous benign, borderline and malignant neoplasms; identifying the aggressive borderline tumours.

  20. Pelvic Inflammatory Disease and the Risk of Ovarian Cancer and Borderline Ovarian Tumors: A Pooled Analysis of 13 Case-Control Studies.

    Science.gov (United States)

    Rasmussen, Christina B; Kjaer, Susanne K; Albieri, Vanna; Bandera, Elisa V; Doherty, Jennifer A; Høgdall, Estrid; Webb, Penelope M; Jordan, Susan J; Rossing, Mary Anne; Wicklund, Kristine G; Goodman, Marc T; Modugno, Francesmary; Moysich, Kirsten B; Ness, Roberta B; Edwards, Robert P; Schildkraut, Joellen M; Berchuck, Andrew; Olson, Sara H; Kiemeney, Lambertus A; Massuger, Leon F A G; Narod, Steven A; Phelan, Catherine M; Anton-Culver, Hoda; Ziogas, Argyrios; Wu, Anna H; Pearce, Celeste L; Risch, Harvey A; Jensen, Allan

    2017-01-01

    Inflammation has been implicated in ovarian carcinogenesis. However, studies investigating the association between pelvic inflammatory disease (PID) and ovarian cancer risk are few and inconsistent. We investigated the association between PID and the risk of epithelial ovarian cancer according to tumor behavior and histotype. We pooled data from 13 case-control studies, conducted between 1989 and 2009, from the Ovarian Cancer Association Consortium (OCAC), including 9,162 women with ovarian cancers, 2,354 women with borderline tumors, and 14,736 control participants. Study-specific odds ratios were estimated and subsequently combined into a pooled odds ratio using a random-effects model. A history of PID was associated with an increased risk of borderline tumors (pooled odds ratio (pOR) = 1.32, 95% confidence interval (CI): 1.10, 1.58). Women with at least 2 episodes of PID had a 2-fold increased risk of borderline tumors (pOR = 2.14, 95% CI: 1.08, 4.24). No association was observed between PID and ovarian cancer risk overall (pOR = 0.99, 95% CI: 0.83, 1.19); however, a statistically nonsignificantly increased risk of low-grade serous tumors (pOR = 1.48, 95% CI: 0.92, 2.38) was noted. In conclusion, PID was associated with an increased risk of borderline ovarian tumors, particularly among women who had had multiple episodes of PID. Although our results indicated a histotype-specific association with PID, the association of PID with ovarian cancer risk is still somewhat uncertain and requires further investigation. © The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  1. KRAS mutation testing in borderline ovarian tumors and low-grade ovarian carcinomas with a rapid, fully integrated molecular diagnostic system.

    Science.gov (United States)

    Sadlecki, Pawel; Antosik, Paulina; Grzanka, Dariusz; Grabiec, Marek; Walentowicz-Sadlecka, Malgorzata

    2017-10-01

    Epithelial ovarian neoplasms are a heterogeneous group of tumors, including various malignancies with distinct clinicopathologic and molecular features. Mutations in BRAF and KRAS genes are the most frequent genetic aberrations found in low-grade serous ovarian carcinomas and serous and mucinous borderline tumors. Implementation of targeted therapeutic strategies requires access to highly specific and highly sensitive diagnostic tests for rapid determination of mutation status. One candidate for such test is fully integrated, real-time polymerase chain reaction-based Idylla™ system for quick and simple detection of KRAS mutations in formaldehyde fixed-paraffin embedded tumor samples. The primary aim of this study was to verify whether fully integrated real-time polymerase chain reaction-based Idylla system may be useful in determination of KRAS mutation status in patients with borderline ovarian tumors and low-grade ovarian carcinomas. The study included tissue specimens from 37 patients with histopathologically verified ovarian masses, operated on at the Department of Obstetrics and Gynecology, Nicolaus Copernicus University Collegium Medicum in Bydgoszcz (Poland) between January 2009 and June 2012. Based on histopathological examination of surgical specimens, 30 lesions were classified as low-grade ovarian carcinomas and 7 as borderline ovarian tumors. Seven patients examined with Idylla KRAS Mutation Test tested positive for KRAS mutation. No statistically significant association was found between the incidence of KRAS mutations and histopathological type of ovarian tumors. Mean survival of the study subjects was 48.51 months (range 3-60 months). Presence of KRAS mutation did not exert a significant effect on the duration of survival in our series. Our findings suggest that Idylla KRAS Mutation Test may be a useful tool for rapid detection of KRAS mutations in ovarian tumor tissue.

  2. Fertility preservation in women with borderline ovarian tumors - how does it impact disease outcome? A cohort study.

    Science.gov (United States)

    Helpman, Limor; Yaniv, Assaf; Beiner, Mario E; Aviel-Ronen, Sarit; Perri, Tamar; Ben-Baruch, Gilad; Hogen Ben-David, Liat; Jakobson-Setton, Ariella; Korach, Jacob

    2017-11-01

    Borderline ovarian tumors are typically indolent neoplasms. Since many are diagnosed in younger women, fertility conservation is an important consideration and has been advocated based on retrospective data. The objective of this study was to identify features impacting on recurrence and survival in a series of borderline ovarian tumors, and to assess the safety of a fertility-sparing approach. A historical cohort study of consecutive borderline ovarian tumors cases treated at a single institution over 30 years (1981-2011). Data on surgical approach (fertility-sparing or otherwise), disease stage, CA125 levels, histological features, adjuvant treatment and follow-up data were collected. Recurrence and survival were assessed using the Kaplan-Meier method and associations with the variables of interest were evaluated using a multivariate Cox proportional hazards model. 213 patients were included. Of 132 women age 40 years and below at diagnosis, 112 (85%) had a fertility-sparing procedure and 60 (46%) had conservation of an involved ovary. Fifty patients (24%) developed recurrences; fertility preservation (hazard ratio = 2.57; 95% confidence interval 1.1-6; p = 0.029) and advanced stage (hazard ratio = 4.15; 95% confidence interval 2.3-7.6; p ovarian tumors carry a good prognosis overall. Fertility preservation is associated with a higher risk of disease relapse; however, as most relapses are localized and may be salvaged with surgical treatment, overall survival is not compromised. © 2017 Nordic Federation of Societies of Obstetrics and Gynecology.

  3. Ultrasound, physical examination, and CA 125 measurement for the detection of recurrence after conservative surgery for early borderline ovarian tumors.

    Science.gov (United States)

    Zanetta, G; Rota, S; Lissoni, A; Meni, A; Brancatelli, G; Buda, A

    2001-04-01

    Borderline ovarian tumors often affect women of childbearing age and the prognosis is outstanding. Given the young age of several patients and the good prognosis, fertility-sparing surgery is considered adequate for stage I tumors. However, women treated conservatively have a relatively small but well-defined risk of recurrence and no study has specifically addressed the optimal follow-up technique. From 1981 to 1997, 164 women underwent fertility-sparing surgery for stage I borderline ovarian tumor and were followed prospectively. After surgery all women underwent physical examination and ultrasound examination every 3 months for 2 years after first diagnosis and every 6 months thereafter. Measurement of serum CA 125 levels was planned every 6 months in patients with a serous tumor. With a median follow-up of 71, months 28 women treated with fertility-sparing surgery (28/164 = 17%) had either recurrence of borderline tumor (23) or recurrence with carcinoma. Complete details of follow-up procedures are available for 24 women and they represent the study population. An abnormal adnexal mass was detected in 18 of 19 women with recurrent borderline tumor. One patient had diagnosis due to persistent free fluid. All five women with invasive carcinoma had diagnosis of a complex adnexal mass. Gynecologic examination was suspicious (palpable mass) in 7 cases and obviously abnormal (large mass or nodules) in another 7. CA 125 serum levels were elevated in 8 cases. Transvaginal ultrasound is currently the most effective diagnostic technique for the follow-up of young patients treated conservatively for early borderline ovarian tumor. Copyright 2001 Academic Press.

  4. Increased risk of borderline ovarian tumors in women with a history of pelvic inflammatory disease: A nationwide population-based cohort study.

    Science.gov (United States)

    Rasmussen, Christina B; Jensen, Allan; Albieri, Vanna; Andersen, Klaus K; Kjaer, Susanne K

    2016-11-01

    Some studies suggest that pelvic inflammatory disease (PID) is a potential risk factor for ovarian cancer. However, only few studies have investigated the association between PID and risk of borderline ovarian tumors. We conducted a population-based cohort study to investigate the association between PID and risk of borderline ovarian tumors. Using various nationwide Danish registries we identified all women in Denmark during 1978-2012, who were born during 1940-1970 (n=1,318,925). Of these, 81,263 women were diagnosed with PID in the study period, and 2736 women had a borderline ovarian tumor (1290 serous and 1344 mucinous). Hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between PID and risk of borderline tumors were estimated using Cox regression models with adjustment for potential confounders. A history of PID was associated with an increased risk of borderline ovarian tumors (HR=1.39; 95% CI: 1.19-1.61). However, histotype-specific analyses revealed significant variation in risk as PID was only associated with an increased risk of serous borderline tumors (HR=1.85; 95% CI: 1.52-2.24), but not with mucinous borderline tumors (HR=1.06; 95% CI: 0.83-1.35). PID is associated with an increased risk of serous borderline tumors. Further research on the potential underlying biological mechanisms and on the identification of the subset of women with PID who are at increased risk of serous borderline tumors is warranted. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Coexistence of borderline ovarian epithelial tumor, primary pelvic hydatid cyst, and lymphoepithelioma-like gastric carcinoma.

    Science.gov (United States)

    Gungor, Tayfun; Altinkaya, Sunduz Ozlem; Sirvan, Levent; Lafuente, Roberto Alvarez; Ceylaner, Serdar

    2011-06-01

    Borderline ovarian tumors (BOTs) represent a heterogeneous group of ovarian epithelial neoplasms. Despite a favorable prognosis, 10-20% of BOTs exhibit progressively worsening clinic. Primary involvement of pelvic organs with echinococcus is very rare. Lymphoepithelioma-like gastric carcinoma is a rare neoplasm of the stomach. A 58-year-old woman referred with abdominal swelling and gastric complaints. Imaging studies revealed a huge cystic mass with multiple septations and solid component, another cystic mass with an appearance of cyst hydatid in the pelvis, and thickening of the small curvature of stomach. Gastroscopy revealed an ulcer with a suspicious malignant appearance, and histology of the endoscopic specimen showed severe chronic inflammation and lymphocytic infiltration. No other involvement of hydatid cyst was detected. In the exploration, there was a 25cm cystic lesion with solid components arising from right ovary, another 6cm cyst over the former, 7cm cystic lesion arising from left ovary, and 10cm mass near the small curvature of the stomach. Excision of the masses; total gastrectomy with esophagojejunal anastomosis; total abdominal hysterectomy; bilateral salpingo-oophorectomy; omentectomy; appendectomy; splenectomy; and pelvic, paraaortic, and coeliac lympadenectomy were performed. Final pathology revealed lymphoepithelioma-like gastric carcinoma, bilateral serous BOT, and hydatid cyst. Hydatid cyst should always be considered in the differential diagnosis of abdominopelvic masses in endemic regions of the world. Preoperative diagnosis of primary pelvic hydatid disease is difficult and awareness of its possibility is very important especially in patients residing in or coming from endemic areas. Copyright © 2011. Published by Elsevier B.V.

  6. Multicystic peritoneal mesothelioma after fertility-sparing surgery for an ovarian tumor of borderline malignancy: A case report

    Directory of Open Access Journals (Sweden)

    Hidetaka Nomura

    2015-02-01

    Full Text Available We report a case of a 19-year-old woman with multicystic peritoneal mesothelioma (MCPM who had previously undergone left adnexectomy due to an ovarian tumor of borderline malignancy at the age of 17 years. Follow-up imaging studies after adnexectomy revealed multiple cystic lesions of increasing size and number, suggesting recurrence of the tumor. Diagnostic laparoscopic surgery was performed, and the cystic lesion was pathologically determined to be MCPM. To our knowledge, this is the first report of MCPM diagnosed and successfully treated by laparoscopic surgery during the course of follow-up for an ovarian tumor. It is important to recognize that MCPM can occur in patients who have previously undergone abdominal surgery, and laparoscopic surgery is recommended for patients of reproductive age, because of the potential risk of infertility associated with extensive pelvic surgery.

  7. Targeted deep sequencing of mucinous ovarian tumors reveals multiple overlapping RAS-pathway activating mutations in borderline and cancerous neoplasms.

    Science.gov (United States)

    Mackenzie, Robertson; Kommoss, Stefan; Winterhoff, Boris J; Kipp, Benjamin R; Garcia, Joaquin J; Voss, Jesse; Halling, Kevin; Karnezis, Anthony; Senz, Janine; Yang, Winnie; Prigge, Elena-Sophie; Reuschenbach, Miriam; Doeberitz, Magnus Von Knebel; Gilks, Blake C; Huntsman, David G; Bakkum-Gamez, Jamie; McAlpine, Jessica N; Anglesio, Michael S

    2015-05-19

    Mucinous ovarian tumors represent a distinct histotype of epithelial ovarian cancer. The rarest (2-4 % of ovarian carcinomas) of the five major histotypes, their genomic landscape remains poorly described. We undertook hotspot sequencing of 50 genes commonly mutated in human cancer across 69 mucinous ovarian tumors. Our goals were to establish the overall frequency of cancer-hotspot mutations across a large cohort, especially those tumors previously thought to be "RAS-pathway alteration negative", using highly-sensitive next-generation sequencing as well as further explore a small number of cases with apparent heterogeneity in RAS-pathway activating alterations. Using the Ion Torrent PGM platform, we performed next generation sequencing analysis using the v2 Cancer Hotspot Panel. Regions of disparate ERBB2-amplification status were sequenced independently for two mucinous carcinoma (MC) cases, previously established as showing ERBB2 amplification/overexpression heterogeneity, to assess the hypothesis of subclonal populations containing either KRAS mutation or ERBB2 amplification independently or simultaneously. We detected mutations in KRAS, TP53, CDKN2A, PIK3CA, PTEN, BRAF, FGFR2, STK11, CTNNB1, SRC, SMAD4, GNA11 and ERBB2. KRAS mutations remain the most frequently observed alteration among MC (64.9 %) and mucinous borderline tumors (MBOT) (92.3 %). TP53 mutation occurred more frequently in carcinomas than borderline tumors (56.8 % and 11.5 %, respectively), and combined IHC and mutation data suggest alterations occur in approximately 68 % of MC and as many as 20 % of MBOT. Proven and potential RAS-pathway activating changes were observed in all but one MC. Concurrent ERBB2 amplification and KRAS mutation were observed in a substantial number of cases (7/63 total), as was co-occurrence of KRAS and BRAF mutations (one case). Microdissection of ERBB2-amplified regions of tumors harboring KRAS mutation suggests these alterations are occurring in the same cell

  8. Comparison of plasma amino acid profile-based index and CA125 in the diagnosis of epithelial ovarian cancers and borderline malignant tumors.

    Science.gov (United States)

    Miyagi, Etsuko; Maruyama, Yasuyo; Mogami, Tae; Numazaki, Reiko; Ikeda, Atsuko; Yamamoto, Hiroshi; Hirahara, Fumiki

    2017-02-01

    We previously developed a new plasma amino acid profile-based index (API) to detect ovarian, cervical, and endometrial cancers. Here, we compared API to serum cancer antigen 125 (CA125) for distinguishing epithelial ovarian malignant tumors from benign growths. API and CA125 were measured preoperatively in patients with ovarian tumors, which were later classified into 59 epithelial ovarian cancers, 21 epithelial borderline malignant tumors, and 97 benign tumors including 40 endometriotic cysts. The diagnostic accuracy and cutoff points of API were evaluated using receiver operating characteristic (ROC) curves. The area under the ROC curves showed the equivalent performance of API and CA125 to discriminate between malignant/borderline malignant and benign tumors (both 0.77), and API was superior to CA125 for discrimination between malignant/borderline malignant lesions and endometriotic cysts (API, 0.75 vs. CA125, 0.59; p tumor marker to detect ovarian cancers and borderline malignancies with a low false-positive rate for endometriosis. A large-scale prospective clinical study using the cutoff value of API determined in this study is warranted to validate API for practical clinical use.

  9. Ten years experience in the management of borderline ovarian tumors at Tom Baker Cancer Centre.

    Science.gov (United States)

    Anfinan, Nisrin; Sait, Khalid; Ghatage, Prafull; Nation, Jill; Chu, Pam

    2011-09-01

    The aim of this study was to review the clinical outcomes of patients with borderline ovarian tumors (BOTs) at Tom Baker Cancer Centre (TBCC) and to assess the value of surgical staging. This retrospective study included 138 patients treated for BOTs at TBCC between January 1994 and December 2005. Patients were divided into two groups: group I with complete surgical staging (n = 89) and group II with incomplete surgical staging (n = 49). This population-based study identified patients using the Alberta Cancer Registry. Charts were reviewed by a single person. Data extracted included demographic information and prognostic factors such as age, histological type, laterality of the cyst, presence of microinvasion, and the type of surgical procedure. Data were extracted and entered into a study database for analysis. Overall survival and overall recurrence-free survival of both groups were calculated using the Kaplan-Meier method. Risk factors for recurrence were analyzed using Cox regression analysis. A total of 138 patients were enrolled, with a mean age of 46 years. The median follow-up time was 37 months. The most common histological type of BOT was the serous type found in 70 (50.7%) patients. Microinvasion was identified in four (2.9%) patients. Twelve patients were found to have implants as result of the staging procedure; two of them were invasive implants and both required chemotherapy. Forty-three (31%) patients had conservative surgery and 95 (68.8%) patients had non-conservative surgery. Nine (6.5%) patients experienced recurrence: five (5.6%) patients in group I versus four (8.2%) patients in group II. The presence of microinvasion is the risk factor for recurrence (P = 0.013). The indications for restaging surgery remain controversial, as there was no difference in recurrence rates observed between the study groups. However, surgical staging is important for identifying invasive extraovarian implants that need to be treated with chemotherapy. For patients

  10. The Serum CA-125 Concentration Data Assists in Evaluating CT Imaging Information When Used to Differentiate Borderline Ovarian Tumor from Malignant Epithelial Ovarian Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Ji Eun; Choi, Hyuck Jae; Kim, Mi Hyun; Cho, Kyoung Sik [University of Ulsan College of Medicine, Asan Medical Center, Seoul (Korea, Republic of)

    2011-08-15

    We wanted to evaluate the diagnostic value of serum CA-125 concentration, when used in combination with the preoperative contrast-enhanced CT results, to differentiate borderline ovarian tumors (BOTs) from stage I malignant epithelial ovarian tumors (MEOTs). Ninety-eight masses (46 BOTs and 52 stage I MEOTs) from 87 consecutive patients (49 with BOTs and 38 with stage I MEOTs) who had undergone preoperative contrast-enhanced computed tomography (CT) and surgical staging were evaluated retrospectively and independently by two radiologists. The preoperative serum CA-125 concentration was measured in all patients. The utility of analyzing serum CA-125 concentration in combination with the CT results was evaluated by receiver operating characteristic (ROC) curve analysis. An irregular tumor surface and lymphadenopathy were predictive of a MEOT. ROC analysis showed that the combination of CT data and the serum CA-125 level resulted in a higher diagnostic performance than did using the CT alone for differentiating BOTs from MEOTs. The areas under the curves (AUCs) without and with the use of the serum CA-125 level data were 0.67 (95% confidence interval [CI]: 0.57-0.77) and 0.78 (95% CI: 0.68-0.85), respectively, for reader 1 (p = 0.029) and 0.71 (95% CI: 0.61-0.80) and 0.81 (95% CI: 0.72-0.89), respectively, for reader 2 (p = 0.009). The serum CA-125 concentration is of additional diagnostic value when used in conjunction with the CT imaging results for differentiating BOTs from MEOTs.

  11. The Serum CA-125 Concentration Data Assists in Evaluating CT Imaging Information When Used to Differentiate Borderline Ovarian Tumor from Malignant Epithelial Ovarian Tumors

    International Nuclear Information System (INIS)

    Shin, Ji Eun; Choi, Hyuck Jae; Kim, Mi Hyun; Cho, Kyoung Sik

    2011-01-01

    We wanted to evaluate the diagnostic value of serum CA-125 concentration, when used in combination with the preoperative contrast-enhanced CT results, to differentiate borderline ovarian tumors (BOTs) from stage I malignant epithelial ovarian tumors (MEOTs). Ninety-eight masses (46 BOTs and 52 stage I MEOTs) from 87 consecutive patients (49 with BOTs and 38 with stage I MEOTs) who had undergone preoperative contrast-enhanced computed tomography (CT) and surgical staging were evaluated retrospectively and independently by two radiologists. The preoperative serum CA-125 concentration was measured in all patients. The utility of analyzing serum CA-125 concentration in combination with the CT results was evaluated by receiver operating characteristic (ROC) curve analysis. An irregular tumor surface and lymphadenopathy were predictive of a MEOT. ROC analysis showed that the combination of CT data and the serum CA-125 level resulted in a higher diagnostic performance than did using the CT alone for differentiating BOTs from MEOTs. The areas under the curves (AUCs) without and with the use of the serum CA-125 level data were 0.67 (95% confidence interval [CI]: 0.57-0.77) and 0.78 (95% CI: 0.68-0.85), respectively, for reader 1 (p = 0.029) and 0.71 (95% CI: 0.61-0.80) and 0.81 (95% CI: 0.72-0.89), respectively, for reader 2 (p = 0.009). The serum CA-125 concentration is of additional diagnostic value when used in conjunction with the CT imaging results for differentiating BOTs from MEOTs.

  12. Second primary or recurrence? Comparative patterns of p53 and K-ras mutations suggest that serous borderline ovarian tumors and subsequent serous carcinomas are unrelated tumors.

    Science.gov (United States)

    Ortiz, B H; Ailawadi, M; Colitti, C; Muto, M G; Deavers, M; Silva, E G; Berkowitz, R S; Mok, S C; Gershenson, D M

    2001-10-01

    The role of serous borderline ovarian tumors (BOTs) in the pathogenesis of serous ovarian carcinomas is unclear. Some authors have compared mutations in serous BOTs to those in serous ovarian carcinomas, but the data on two common oncogenes, p53 and K-ras, remain inconclusive. To further clarify the relationship between the two tumors, we performed mutational analysis on tumors from a set of eight patients who first presented with advanced-stage serous BOTs and later developed grade 1 serous carcinomas. Epithelium from eight advanced-stage serous BOTs and subsequent grade 1 papillary serous carcinomas was microdissected and retrieved using a PixCell laser-capture microscope. Stroma was dissected as an internal control. The DNA was extracted with proteinase K and analyzed by single-strand conformational polymorphism-PCR for p53 and K-ras mutations. Bands with altered motility were analyzed by direct cycle sequencing. Seven of eight patients demonstrated different mutations in the secondary tumor compared with the primary tumor. For three patients, p53 mutations were identified in the BOTs that were absent from the carcinomas, suggesting a nonclonal origin for the carcinomas. These findings are consistent with the hypothesis that advanced-stage serous BOTs represent a distinct pathological entity compared with grade 1 serous epithelial ovarian carcinoma.

  13. Immunohistochemistry with apoptotic-antiapoptotic proteins (p53, p21, bax, bcl-2, c-kit, telomerase, and metallothionein as a diagnostic aid in benign, borderline, and malignant serous and mucinous ovarian tumors

    Directory of Open Access Journals (Sweden)

    Ozer Hatice

    2012-09-01

    Full Text Available Abstract Background In many tumors including ovarian cancer, cell proliferation and apoptosis are important in pathogenesis and there are many alterations in most of the genes related to the cell cycle. This study was designed to evaluate immunohistochemistry with apoptotic-antiapoptotic proteins (p53, p21, bax, and bcl-2, c-kit, telomerase, and metallothionein as a diagnostic aid in typing of benign, borderline, and malignant serous and mucinous ovarian tumors. Methods Total of 68 ovarian tumors, 25 benign [13 (19.1% serous and12 (17.6% mucinous], 16 borderline [9 (13.2% serous and 7(10.3% mucinous], and 27 malignant ovarian tumors [24 (35.3% serous and 3 (4.4% mucinous tumors] were included in the study. Immunohistochemical expression of p53, p21, bax, bcl–2, telomerase, c-kit, and metallothionein were evaluated. Results When all 68 cases were evaluated as benign, borderline, and malignant ovarian tumors without considering histopathological subtypes, the p53, p21, bax and metallothionein showed significantly higher staining scores in the borderline and malignant ones (p  Conclusions In conclusion, p53, p21, bax, c-kit, and metallothionein may be helpful for the typing of ovarian tumors as benign, borderline and malignant or serous and mucinous. p53, p21, bax, c-kit, and metallothionein may have different roles in the pathogenesis of ovarian tumor types. p53 and metallothionein may be helpful in the typing of borderline and malignant ovarian tumors. The immunohistochemical staining with bcl-2 and telomerase may not provide meaningful contribution for the typing of ovarian tumors. Virtual slide The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2013030833768498

  14. Is CA-125 an additional help to radiologic findings for differentiation borderline ovarian tumor from stage I carcinoma?

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eun Joo; Kim, See Hyung; Kim, Young Hwan; Lee, Hee Jung (Dept. of Radiology, Keimyung Univ. Dongsan Hospital, College of Medicine, Daegu (Korea, Republic of)), email: kseehdr@dsmc.or.kr

    2011-05-15

    Background Borderline ovarian tumors (BOTs) are difficult to differentiate from stage I carcinoma using radiological findings. Little is known about the correlation between CA-125 levels and radiological findings for predicting BOTs or carcinoma. Purpose To assess the role of CA-125, in addition to that of radiological findings, in differentiating BOTs from stage I carcinoma. Material and Methods The study received institutional review board approval, with waiver of informed consent. We evaluated 100 patients (two groups: BOT, 58 patients; stage I carcinoma, 42 patients) using radiological findings, including location and size of each tumor, number and size of septations, papillary projections and vegetations, peritoneal implants, ascites, and preoperative CA-125 levels. The differences in CA-125 levels according to bilateral location, solid components, and thickness of septations between the two groups were evaluated using the McNemar test. Correlations of CA-125 level to size and number of septations were evaluated by the independent sample t test. Results No statistical correlation was found between CA-125 level and location, size, and number of septations between the two groups. Solid components within the tumors were similar in the two groups, but the CA-125 level was significantly higher in stage I carcinoma than in BOTs. The number of septations per tumor was similar in the two groups; thick septations were more frequent in stage I carcinoma than in BOTs, and a significantly higher titer of CA-125 was found in stage I carcinoma. Discriminant analysis of solid components and thickness of septations resulted in accurate diagnosis of 70.6% of the tumors (80.6% of BOTs and 69.7% of stage I carcinomas). Conclusion CA-125 levels for solid components and thickness of septations are lower in BOTs. These may be helpful in predicting the risk of carcinoma, even if BOTs cannot be conclusively differentiated from stage I carcinoma

  15. Is CA-125 an additional help to radiologic findings for differentiation borderline ovarian tumor from stage I carcinoma?

    International Nuclear Information System (INIS)

    Lee, Eun Joo; Kim, See Hyung; Kim, Young Hwan; Lee, Hee Jung

    2011-01-01

    Background Borderline ovarian tumors (BOTs) are difficult to differentiate from stage I carcinoma using radiological findings. Little is known about the correlation between CA-125 levels and radiological findings for predicting BOTs or carcinoma. Purpose To assess the role of CA-125, in addition to that of radiological findings, in differentiating BOTs from stage I carcinoma. Material and Methods The study received institutional review board approval, with waiver of informed consent. We evaluated 100 patients (two groups: BOT, 58 patients; stage I carcinoma, 42 patients) using radiological findings, including location and size of each tumor, number and size of septations, papillary projections and vegetations, peritoneal implants, ascites, and preoperative CA-125 levels. The differences in CA-125 levels according to bilateral location, solid components, and thickness of septations between the two groups were evaluated using the McNemar test. Correlations of CA-125 level to size and number of septations were evaluated by the independent sample t test. Results No statistical correlation was found between CA-125 level and location, size, and number of septations between the two groups. Solid components within the tumors were similar in the two groups, but the CA-125 level was significantly higher in stage I carcinoma than in BOTs. The number of septations per tumor was similar in the two groups; thick septations were more frequent in stage I carcinoma than in BOTs, and a significantly higher titer of CA-125 was found in stage I carcinoma. Discriminant analysis of solid components and thickness of septations resulted in accurate diagnosis of 70.6% of the tumors (80.6% of BOTs and 69.7% of stage I carcinomas). Conclusion CA-125 levels for solid components and thickness of septations are lower in BOTs. These may be helpful in predicting the risk of carcinoma, even if BOTs cannot be conclusively differentiated from stage I carcinoma

  16. The Putative Role of TP53 Alterations and p53 Expression in Borderline Ovarian Tumors - Correlation with Clinicopathological Features and Prognosis: A Mini-Review

    Science.gov (United States)

    Semczuk, Andrzej; Gogacz, Marek; Semczuk-Sikora, Anna; Jóźwik, Maciej; Rechberger, Tomasz

    2017-01-01

    Borderline ovarian tumors (BOTs) represent an independent group among ovarian malignancies, being diagnosed at clinical stage earlier than invasive ovarian carcinomas (OCs) and characterized by a rather favorable outcome after careful surgical management. Data published worldwide showed a substantial discordance of p53 expression in BOTs. The purpose of this work was to present the current status of knowledge on the significance of TP53 gene and p53 protein product alterations in BOTs. In general, higher p53 expression patterns were reported for ovarian malignancies compared to BOTs. Serous, mucinous, and endometrioid BOTs differ substantially in relation to p53 immunostaining, but data concerning the relationship between the protein's immunoreactivity and other clinico-pathological variables are scarce. Finally, reports published to date support the view that TP53 alterations may not be commonly associated with the borderline phenotype of ovarian tumors but they probably occur during the development of invasive OCs. In light of these uncertainties, the impact of TP53 alterations and p53 expression on overall survival in women affected by BOTs requires further multi-institutional studies in large cohorts of patients. PMID:28928856

  17. Mutant epidermal growth factor receptor in benign, borderline, and malignant ovarian tumors

    DEFF Research Database (Denmark)

    Steffensen, Karina Dahl; Waldstrøm, Marianne; Olsen, Dorte Aalund

    2008-01-01

    . RESULTS: None of the tissue samples was positive for the EGFRvIII mutation neither at the mRNA level nor at the protein level. CONCLUSIONS: The EGFRvIII mutation seems to be very rare in ovarian tissue. Our data indicate that EGFRvIII is not a part of the malignant phenotype in ovarian cancer and should...

  18. [External multicentric validation of two scores predicting the risk of relapse in patients with borderline ovarian tumors: The nomogram of Bendifallah and the score of Ouldamer].

    Science.gov (United States)

    Pais, Prescilla; Huchon, Cyrille; Chevrot, Audrey; Cohen, Julien; Fauconnier, Arnaud; Rouzier, Roman; Mimouni, Myriam

    2017-09-01

    Borderline ovarian tumors are rare and can occur in young women. For these patients, a fertility sparing surgery should be discussed. Two predicting borderline ovarian tumor relapse risk models were developed in 2014 (Nomogram of Bendifallah) and 2017 (Score of Ouldamer). This study aimed to valid in an external population, these two scores using a multi-institutional BOT database. In this bicentric and retrospective study, all consecutive patients comprising the variable nomogram documented treated between January 2006 and December 2012 for BOT in centre hospitalier de Poissy-Saint-Germain and hôpital René-Huguenin were included. A ROC model was established for each predicting scores. Sixty-five patients were included in the study. Twelve patients showed a recurrence (19%), three of them experienced an infiltrative cancer (5%). The median time of recurrence was 25 months (range: 8-115). The concordance index for the Nomogram of Bendifallah and the Score of Ouldamer were 0.88 (IC 95% [0.78-0.98]) and 0.87 (IC 95% [0.77-0.96]) respectively. This study from an independent population valids the Bendifallah nomogram and Ouldamer score for clinical use in predicting borderline ovarian recurrence. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  19. A nationwide study of ovarian serous borderline tumors in Denmark 1978-2002. Risk of recurrence, and development of ovarian serous carcinoma.

    Science.gov (United States)

    Hannibal, Charlotte Gerd; Vang, Russell; Junge, Jette; Frederiksen, Kirsten; Kurman, Robert J; Kjaer, Susanne K

    2017-01-01

    Absolute risk and risk factors for recurrence and ovarian serous carcinoma following ovarian serous borderline tumors (SBTs) is not well-established. We included all women with SBTs in Denmark, 1978-2002. Diagnoses were confirmed by centralized pathology review and classified as atypical proliferative serous tumor (APST) or noninvasive low-grade serous carcinoma (LGSC). Implants were classified as noninvasive or invasive. Medical records were collected and reviewed, and follow-up was obtained. Subsequent diagnoses were also confirmed by centralized pathology review. We examined absolute risk and risk factors for recurrent APST and serous carcinoma using Cox regression. The absolute serous carcinoma risk after, respectively, 5 and 20years was 5.0% and 13.9% for noninvasive LGSC, and 0.9% and 3.7% for APST. Serous carcinoma risk was significantly higher following noninvasive LGSC compared with APST among stage I patients/patients without implants (HR=5.3; 95% CI: 1.7-16.3), whereas no significant association with tumor type was found in advanced stage patients/patients with implants. Advanced stage - notably invasive implants - bilaterality, surface involvement, and residual disease increased serous carcinoma risk. However, women with stage I APST also had a higher risk than the general population. This largest population-based cohort of verified SBTs revealed that women with noninvasive LGSC are significantly more likely to develop serous carcinoma than women with APST, which could not entirely be explained by invasive implants. Although invasive implants was a strong risk factor for serous carcinoma, even women with stage I APST were at increased risk compared with the general population. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. TGF-beta induces serous borderline ovarian tumor cell invasion by activating EMT but triggers apoptosis in low-grade serous ovarian carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Jung-Chien Cheng

    Full Text Available Apoptosis in ovarian surface epithelial (OSE cells is induced by transforming growth factor-beta (TGF-β. However, high-grade serous ovarian carcinomas (HGC are refractory to the inhibitory functions of TGF-β; their invasiveness is up-regulated by TGF-β through epithelial-mesenchymal transition (EMT activation. Serous borderline ovarian tumors (SBOT have been recognized as distinct entities that give rise to invasive low-grade serous carcinomas (LGC, which have a relatively poor prognosis and are unrelated to HGC. While it is not fully understood how TGF-β plays disparate roles in OSE cells and its malignant derivative HGC, its role in SBOT and LGC remains unknown. Here we demonstrate the effects of TGF-β on cultured SBOT3.1 and LGC-derived MPSC1 cells, which express TGF-β type I and type II receptors. TGF-β treatment induced the invasiveness of SBOT3.1 cells but reduced the invasiveness of MPSC1 cells. The analysis of apoptosis, which was assessed by cleaved caspase-3 and trypan blue exclusion assay, revealed TGF-β-induced apoptosis in MPSC1, but not SBOT3.1 cells. The pro-apoptotic effect of TGF-β on LGC cells was confirmed in another immortalized LGC cell line ILGC. TGF-β treatment led to the activation of Smad3 but not Smad2. The specific TβRI inhibitor SB431542 and TβRI siRNA abolished the SBOT3.1 invasion induced by TGF-β, and it prevented TGF-β-induced apoptosis in MPSC1 cells. In SBOT3.1 cells, TGF-β down-regulated E-cadherin and concurrently up-regulated N-cadherin. TGF-β up-regulated the expression of the transcriptional repressors of E-cadherin, Snail, Slug, Twist and ZEB1. In contrast, co-treatment with SB431542 and TβRI depletion by siRNA abolished the effects of TGF-β on the relative cadherin expression levels and that of Snail, Slug, Twist and ZEB1 as well. This study demonstrates dual TGF-β functions: the induction of SBOT cell invasion by EMT activation and apoptosis promotion in LGC cells.

  1. [A case of disseminated intravascular coagulation--a paraneoplastic manifestation of a borderline ovarian tumor].

    Science.gov (United States)

    Bălănescu, I; Coliţă, D; Moicean, A; Duţu, R; Stănculescu, M; Voinea, S

    1998-01-01

    A 24-year-old-woman was admitted because of disseminated intravascular coagulation (DIC), menometrorrhagia and galactorrhea. The investigations performed showed a right adnexal tumor after the equilibration of DIC with plasma substitution, we performed a right adnexectomy with limited excision of peritoneal. The pathologic examination showed a focus of endometriosis on the right ovary who had a polycystic look and a right adnexal fibromyxoma (premalignant lesion). The post operative evolution was good, with the loss of entire onco-hemato-endocrinologic picture. We describe the interrelation between DIC (paraneoplastic syndrome), menometrorrhagia and galactorrhea, the pathologic hypothesis and the treatment of DIC.

  2. Fertility sparing treatment in borderline ovarian tumours

    Science.gov (United States)

    Alvarez, Rosa Maria; Vazquez-Vicente, Daniel

    2015-01-01

    Borderline ovarian tumours are low malignant potential tumours. They represent 10–15% of all epithelial ovarian malignancies. Patients with this type of tumour are younger at the time of diagnosis than patients with invasive ovarian cancer. Most of them are diagnosed in the early stages and have an excellent prognosis. It has been quite clearly established that the majority of borderline ovarian tumours should be managed with surgery alone. Because a high proportion of women with this malignancy are young and the prognosis is excellent, the preservation of fertility is an important issue in the management of these tumours. In this systemic review of the literature, we have evaluated in-depth oncological safety and reproductive outcomes in women with borderline ovarian tumours treated with fertility-sparing surgery, reviewing the indications, benefits, and disadvantages of each type of conservative surgery, as well as new alternative options to surgery to preserve fertility. PMID:25729420

  3. The value of random biopsies, omentectomy, and hysterectomy in operations for borderline ovarian tumors

    DEFF Research Database (Denmark)

    Kristensen, Gitte Schultz; Schledermann, Doris; Mogensen, Ole

    2014-01-01

    -appearing tissues leads to the finding of microscopic disease. To evaluate the value of random biopsies, omentectomy, and hysterectomy in operations for BOT, the macroscopic and microscopic findings in a cohort of these patients were reviewed retrospectively. MATERIALS: Women treated for BOT at Odense University...... Hospital from 2007 to 2011 were eligible for this study. Data were extracted from electronic records. Intraoperative assessment of tumor spread (macroscopic disease) and the microscopic evaluation of removed tissues were the main outcome measures. RESULTS: The study included 75 patients, 59 (78.......7%) in International Federation of Gynecology and Obstetrics stage I, 9 (12%) in stage II, and 7 (9.3%) in stage III. The histologic subtypes were serous (68%), mucinous (30.7%), and Brenner type (1.3%). Macroscopically radical surgery was performed in 62 patients (82.7%), and 46 (61.3%) received complete staging...

  4. Polytomous diagnosis of ovarian tumors as benign, borderline, primary invasive or metastatic: development and validation of standard and kernel-based risk prediction models

    Directory of Open Access Journals (Sweden)

    Testa Antonia C

    2010-10-01

    Full Text Available Abstract Background Hitherto, risk prediction models for preoperative ultrasound-based diagnosis of ovarian tumors were dichotomous (benign versus malignant. We develop and validate polytomous models (models that predict more than two events to diagnose ovarian tumors as benign, borderline, primary invasive or metastatic invasive. The main focus is on how different types of models perform and compare. Methods A multi-center dataset containing 1066 women was used for model development and internal validation, whilst another multi-center dataset of 1938 women was used for temporal and external validation. Models were based on standard logistic regression and on penalized kernel-based algorithms (least squares support vector machines and kernel logistic regression. We used true polytomous models as well as combinations of dichotomous models based on the 'pairwise coupling' technique to produce polytomous risk estimates. Careful variable selection was performed, based largely on cross-validated c-index estimates. Model performance was assessed with the dichotomous c-index (i.e. the area under the ROC curve and a polytomous extension, and with calibration graphs. Results For all models, between 9 and 11 predictors were selected. Internal validation was successful with polytomous c-indexes between 0.64 and 0.69. For the best model dichotomous c-indexes were between 0.73 (primary invasive vs metastatic and 0.96 (borderline vs metastatic. On temporal and external validation, overall discrimination performance was good with polytomous c-indexes between 0.57 and 0.64. However, discrimination between primary and metastatic invasive tumors decreased to near random levels. Standard logistic regression performed well in comparison with advanced algorithms, and combining dichotomous models performed well in comparison with true polytomous models. The best model was a combination of dichotomous logistic regression models. This model is available online

  5. Fas and Fas ligand in cyst fluids, serum and tumors of patients with benign and (borderline) malignant ovarian tumors

    NARCIS (Netherlands)

    Arts, HJG; De Jong, S; Hollema, H; Ten Hoor, KA; De Vries, EGE; Van Der Zee, AGJ

    Drug resistance in ovarian cancer treatment urges the exploration of new targets for drugs against this malignancy. Fas is a cell membrane receptor which, after engagement with Fas ligand (FasL), triggers apoptotic death. In this study Fas and FasL levels in cyst fluids and sera of patients with

  6. Inhibition of p53 represses E-cadherin expression by increasing DNA methyltransferase-1 and promoter methylation in serous borderline ovarian tumor cells.

    Science.gov (United States)

    Cheng, J-C; Auersperg, N; Leung, P C K

    2011-09-15

    The mechanisms underlying the progression of noninvasive serous borderline ovarian tumors (SBOT) to low-grade invasive carcinomas are poorly understood. We recently showed that inhibition of p53 induces SBOT invasion by activating the PI3K/Akt pathway and transcriptionally repressing E-cadherin. In human cancers, aberrant DNA methylation is a common phenomenon, and it is thought to be involved in the progression from noninvasive to invasive ovarian carcinomas. In this study, we tested the hypothesis that inhibition of p53 downregulates E-cadherin by regulating the methylation of its promoter in SBOT cells. Here, we show that DNA methyltransferase-1 (DNMT1), but not DNMT3a or DNMT3b, was increased in SV40 LT-infected SBOT4 cells, SBOT4-LT and the low-grade invasive serous ovarian carcinoma-derived cell line MPSC1. Treatment with 5-Aza-dC, a DNMT1 inhibitor, restored E-cadherin promoter methylation and expression, and inhibited cell invasion in both invasive SBOT4-LT and MPSC1 cells. Moreover, knockdown of endogenous p53 using siRNA in SBOT3.1 cells induced DNMT1 expression and led to an increase in E-cadherin promoter methylation. Additionally, activation of the PI3K/Akt pathway is required for p53 inhibition-induced DNMT1 expression. The increase in DNMT1 was associated with the inhibition of p53-induced downregulation of E-cadherin and cell invasion. Our findings show an important role for p53 in the progression of SBOT to an invasive carcinoma, and suggest that downregulation of E-cadherin by DNMT1-mediated promoter methylation contributes to this process.

  7. Frequency of papillary tubal hyperplasia (PTH), salpingoliths and transition from adenoma to borderline ovarian tumors (BOT): A systematic analysis of 74 BOT with different histologic types.

    Science.gov (United States)

    Horn, Lars-Christian; Angermann, Karolin; Hentschel, Bettina; Einenkel, Jens; Höhn, Anne Kathrin

    2017-04-01

    Borderline ovarian tumors (BOT) arise from cystadenomas and represent a transition step within the development of low-grade ovarian carcinomas (Type I tumors). That pathway mirrors the adenoma-to-carcinoma sequence known for colorectal cancer. It has been suggested that papillary tubal hyperplasia (PTH) and salpingoliths may be associated with the development of BOT. To evaluate the frequency of the presence of benign cystadenoma and its transition to BOT in a given patient as well as the presence of PTH and salpingoliths we re-valuated in 74 consecutive cases of BOT with different histologic types. The majority of cases represented serous-BOT (60.8%), followed by mucinous BOT (25.7%), other histologic types were rare. 86.5% showed an adenoma-BOT sequence, which was seen in all mucinous BOT but was missed in 15.6% of serous BOT. Two cases had salpingoliths without associated PTH. PTH was seen in four out of the 74 (5.4%) BOT and occurred only in cases with serous histology. The vast majority of BOT represent a transition from benign cystadenoma to BOT in cases with mucinous and serous histology. Salpingoliths are rarely seen in association with BOT and occurred exclusively in BOT with serous histology. PTH may represent a distinct lesion but is rarely seen in association with BOT, especially in those with non-serous histology. Further studies are needed to evaluate the frequency and pathogenetic association of PTH with BOT. Copyright © 2017 Elsevier GmbH. All rights reserved.

  8. Pelvic Inflammatory Disease and the Risk of Ovarian Cancer and Borderline Ovarian Tumors: A Pooled Analysis of 13 Case-Control Studies

    NARCIS (Netherlands)

    Rasmussen, C.B.; Kjaer, S.K.; Albieri, V.; Bandera, E.V.; Doherty, J.A.; Hogdall, E.; Webb, P.M.; Jordan, S.J.; Rossing, M.A.; Wicklund, K.G.; Goodman, M.T.; Modugno, F.; Moysich, K.B.; Ness, R.B.; Edwards, R.P.; Schildkraut, J.M.; Berchuck, A.; Olson, S.H.; Kiemeney, L.A.L.M.; Massuger, L.F.A.G.; Narod, S.A.; Phelan, C.M.; Anton-Culver, H.; Ziogas, A.; Wu, A.H.; Pearce, C.L.; Risch, H.A.; Jensen, A.

    2017-01-01

    Inflammation has been implicated in ovarian carcinogenesis. However, studies investigating the association between pelvic inflammatory disease (PID) and ovarian cancer risk are few and inconsistent. We investigated the association between PID and the risk of epithelial ovarian cancer according to

  9. EGF-induced EMT and invasiveness in serous borderline ovarian tumor cells: a possible step in the transition to low-grade serous carcinoma cells?

    Science.gov (United States)

    Cheng, Jung-Chien; Auersperg, Nelly; Leung, Peter C K

    2012-01-01

    In high-grade ovarian cancer cultures, it has been shown that epidermal growth factor (EGF) induces cell invasion by activating an epithelial-mesenchymal transition (EMT). However, the effect of EGF on serous borderline ovarian tumors (SBOT) and low-grade serous carcinomas (LGC) cell invasion remains unknown. Here, we show that EGF receptor (EGFR) was expressed, that EGF treatment increased cell migration and invasion in two cultured SBOT cell lines, SBOT3.1 and SV40 large T antigen-infected SBOT cells (SBOT4-LT), and in two cultured LGC cell lines, MPSC1 and SV40 LT/ST-immortalized LGC cells (ILGC). However, EGF induced down-regulation of E-cadherin and concurrent up-regulation of N-cadherin in SBOT cells but not in LGC cells. In SBOT cells, the expression of the transcriptional repressors of E-cadherin, Snail, Slug and ZEB1 were increased by EGF treatment. Treatment with EGF led to the activation of the downstream ERK1/2 and PI3K/Akt. The MEK1 inhibitor PD98059 diminished the EGF-induced cadherin switch and the up-regulation of Snail, Slug and ZEB1 and the EGF-mediated increase in SBOT cell migration and invasion. The PI3K inhibitor LY294002 had similar effects, but it could not block the EGF-induced up-regulation of N-cadherin and ZEB1. This study demonstrates that EGF induces SBOT cell migration and invasion by activating EMT, which involves the activation of the ERK1/2 and PI3K/Akt pathways and, subsequently, Snail, Slug and ZEB1 expression. Moreover, our results suggest that there are EMT-independent mechanisms that mediate the EGF-induced LGC cell migration and invasion.

  10. EGF-induced EMT and invasiveness in serous borderline ovarian tumor cells: a possible step in the transition to low-grade serous carcinoma cells?

    Directory of Open Access Journals (Sweden)

    Jung-Chien Cheng

    Full Text Available In high-grade ovarian cancer cultures, it has been shown that epidermal growth factor (EGF induces cell invasion by activating an epithelial-mesenchymal transition (EMT. However, the effect of EGF on serous borderline ovarian tumors (SBOT and low-grade serous carcinomas (LGC cell invasion remains unknown. Here, we show that EGF receptor (EGFR was expressed, that EGF treatment increased cell migration and invasion in two cultured SBOT cell lines, SBOT3.1 and SV40 large T antigen-infected SBOT cells (SBOT4-LT, and in two cultured LGC cell lines, MPSC1 and SV40 LT/ST-immortalized LGC cells (ILGC. However, EGF induced down-regulation of E-cadherin and concurrent up-regulation of N-cadherin in SBOT cells but not in LGC cells. In SBOT cells, the expression of the transcriptional repressors of E-cadherin, Snail, Slug and ZEB1 were increased by EGF treatment. Treatment with EGF led to the activation of the downstream ERK1/2 and PI3K/Akt. The MEK1 inhibitor PD98059 diminished the EGF-induced cadherin switch and the up-regulation of Snail, Slug and ZEB1 and the EGF-mediated increase in SBOT cell migration and invasion. The PI3K inhibitor LY294002 had similar effects, but it could not block the EGF-induced up-regulation of N-cadherin and ZEB1. This study demonstrates that EGF induces SBOT cell migration and invasion by activating EMT, which involves the activation of the ERK1/2 and PI3K/Akt pathways and, subsequently, Snail, Slug and ZEB1 expression. Moreover, our results suggest that there are EMT-independent mechanisms that mediate the EGF-induced LGC cell migration and invasion.

  11. Clinical Significance of Microsatellite Instability in Sporadic Epithelial Ovarian Tumors

    OpenAIRE

    Yoon, Bo-Sung; Kim, Young-Tae; Kim, Jae-Hoon; Kim, Sang-Wun; Nam, Eun-Ji; Cho, Nam-Hoon; Kim, Jae-Wook; Kim, Sunghoon

    2008-01-01

    Purpose We evaluated the expression of microsatellite instability (MSI) in sporadic ovarian tumors using 5 standard and 9 new MSI markers to determine the clinical significance of MSI in sporadic epithelial ovarian tumors. Materials and Methods MSI was examined in 21 borderline and 25 malignant ovarian tumors. Polymerase chain reaction (PCR) was performed using the 5 markers recommended by the National Cancer Institute (NCI) for colon cancer and 9 additional markers. MSI was determined using ...

  12. Increased risk for ovarian cancer and borderline ovarian tumours in subfertile women with endometriosis

    NARCIS (Netherlands)

    Buis, C. C. M.; van Leeuwen, F. E.; Mooij, T. M.; Burger, C. W.; Lambalk, Cornelis B.; Kortman, Marian; Laven, Joop S. E.; Jansen, Cees A. M.; Helmerhorst, Frans M.; Cohlen, Ben J.; Willemsen, Wim N. P.; Smeenk, Jesper M. J.; Simons, Arnold H. M.; van der Veen, Fulco; Evers, Johannes L. H.; van Dop, Peter A.; Macklon, Nicholas S.

    2013-01-01

    Is ovarian or extra-ovarian endometriosis associated with an increased risk of ovarian cancer and borderline ovarian tumours (BOT)? We found a 3- to 8-fold increased risk of ovarian tumours associated with endometriosis: the magnitude of the risk increase depended on the definition of endometriosis.

  13. Molecular characterization of 103 ovarian serous and mucinous tumors.

    Science.gov (United States)

    Vereczkey, Ildikó; Serester, Orsolya; Dobos, Judit; Gallai, Mónika; Szakács, Orsolya; Szentirmay, Zoltán; Tóth, Erika

    2011-09-01

    The pathogenesis of ovarian carcinomas is heterogeneous, with even the same entities showing great variance. In our study we investigated the mutations of the BRAF, KRAS, and p53 genes in serous and mucinous borderline tumors and in low grade and high grade serous and mucinous tumors. The mutations of BRAF and KRAS genes have been shown in 60% of borderline and low grade (well differentiated) serous and mucinous tumors, but very rarely in high grade (moderately and poorly differentiated) carcinomas. However mutations of p53 are very common in high grade tumors and this indicates a "dualistic" model of ovarian tumorigenesis. A total of 80 serous tumors, including serous borderline, low grade and high grade tumors, and 23 mucinous tumors, including borderline and invasive tumors were analysed for BRAF and KRAS mutations using real time PCR method followed by melting point analysis. P53 mutation was investigated by immunohistochemistry. We assumed mutation of the p53 gene when 100% of tumor cells showed strong nuclear positivity. We observed differences in genetic alterations in the development of the low grade tumors and between low and high grade tumors too. In some bilateral or stage II-III cases we observed differences between the mutation status of the left and right ovarian tumors and between the primary tumor and its implants. In one case in a tumor with micropapillary pattern showing high grade nuclear atypia we could detect mutations in both KRAS and p53 genes. The majority of our mucinous ovarian tumor cases showed a KRAS mutation. We have not found mutations of the BRAF and p53 genes in these cases. We have found as have others, that there is a dualistic pathway of ovarian carcinogenesis. In the majority of cases, low grade epithelial tumors develop in a stepwise manner due to genetic alterations of the members of MAP-kinase pathway; however mutation of the p53 gene is the key event in the development of high grade tumors.

  14. Ultrasound-Guided Laparoscopic Ovarian Wedge Resection in Recurrent Serous Borderline Ovarian Tumours.

    Science.gov (United States)

    Jones, Benjamin P; Saso, Srdjan; Farren, Jessica; El-Bahrawy, Mona; Ghaem-Maghami, Sadaf; Smith, J Richard; Yazbek, Joseph

    2017-11-01

    The aim of this study was to demonstrate the use of intraoperative ultrasound-guided ovarian wedge resection in the treatment of recurrent serous borderline ovarian tumors (sBOTs) that are too small to be visualized laparoscopically. This was a prospective analysis of all women with recurrent sBOTs that were not visible laparoscopically, who underwent intraoperative ultrasound-guided ovarian wedge resection between January 2015 and December 2016 at the West London Gynaecological Cancer Centre, Imperial College NHS Trust, London, United Kingdom. We evaluated 7 patients, with a median age of 35 years (range, 28-39 years). Six women were nulliparous, whereas 1 woman had a single child. Previous surgical intervention left 5 women with a single ovary, whereas the remaining 2 had previous ovarian-sparing surgery. The median size of recurrence was 18 mm (range, 12-37 mm). All women underwent uncomplicated intraoperative guided ovarian wedge resections. Histological assessment confirmed sBOT in all 7 cases. Six of the women remain disease-free. One woman recurred postoperatively with her third recurrence, who previously had bilateral disease and noninvasive implants with microinvasive disease and micropapillary pattern. No cases progressed to invasive disease. The median follow-up time was 12 months (range, 1-20 months). One pregnancy has been achieved postoperatively but resulted in miscarriage. Continuous intraoperative ultrasound can be used to facilitate complete tumor excision in recurrent sBOT while minimizing the removal of ovarian tissue in women with recurrent sBOT. It is essential that surgical techniques evolve simultaneously with diagnostic imaging modalities to enable surgeons to treat such pathology.

  15. Molecular Subtyping of Serous Ovarian Tumors Reveals Multiple Connections to Intrinsic Breast Cancer Subtypes

    Science.gov (United States)

    Jönsson, Jenny-Maria; Johansson, Ida; Dominguez-Valentin, Mev; Kimbung, Siker; Jönsson, Mats; Bonde, Jesper Hansen; Kannisto, Päivi; Måsbäck, Anna; Malander, Susanne; Nilbert, Mef; Hedenfalk, Ingrid

    2014-01-01

    Objective Transcriptional profiling of epithelial ovarian cancer has revealed molecular subtypes correlating to biological and clinical features. We aimed to determine gene expression differences between malignant, benign and borderline serous ovarian tumors, and investigate similarities with the well-established intrinsic molecular subtypes of breast cancer. Methods Global gene expression profiling using Illumina's HT12 Bead Arrays was applied to 59 fresh-frozen serous ovarian malignant, benign and borderline tumors. Nearest centroid classification was performed applying previously published gene profiles for the ovarian and breast cancer subtypes. Correlations to gene expression modules representing key biological breast cancer features were also sought. Validation was performed using an independent, publicly available dataset. Results 5,944 genes were significantly differentially expressed between benign and malignant serous ovarian tumors, with cell cycle processes enriched in the malignant subgroup. Borderline tumors were split between the two clusters. Significant correlations between the malignant serous tumors and the highly aggressive ovarian cancer signatures, and the basal-like breast cancer subtype were found. The benign and borderline serous tumors together were significantly correlated to the normal-like breast cancer subtype and the ovarian cancer signature derived from borderline tumors. The borderline tumors in the study dataset, in addition, also correlated significantly to the luminal A breast cancer subtype. These findings remained when analyzed in an independent dataset, supporting links between the molecular subtypes of ovarian cancer and breast cancer beyond those recently acknowledged. Conclusions These data link the transcriptional profiles of serous ovarian cancer to the intrinsic molecular subtypes of breast cancer, in line with the shared clinical and molecular features between high-grade serous ovarian cancer and basal-like breast

  16. Management and prognosis of endometrioid borderline tumors of the ovary.

    Science.gov (United States)

    Uzan, C; Berretta, R; Rolla, M; Gouy, S; Fauvet, R; Darai, E; Duvillard, P; Morice, P

    2012-09-01

    The Endometrioid Borderline ovarian tumor (EBOT) is the third most common histological subtype of borderline ovarian tumors. Very little is known about the prognosis and management of this entity. This paper consists of a review of the literature and an analysis of clinical series. A review of the literature on this topic was conducted identifying series reporting consecutive cases of EBOT using 2 search engines (MEDLINE and Pubmed). Personal data on this topic have been included and concern a series of patients treated between 1985 and 2009 for EBOT. These cases included in this series had complete data concerning patient management and follow-up > 12 months. 16 patients were studied: 7 had been treated conservatively and 9 radically. All 16/16 patients had stage I disease at the initial diagnosis but one patient had also developed synchronous endometrioid adenocarcinoma of the uterine corpus. After a median time of 24 months (range, 12-132) post treatment, one (1/16) patient had developed two recurrences. She remains disease-free 42 months after the end of treatment of the last recurrence. These data were compared to the results of 4 series previously reported in the literature. In fact, the present series reports on the first recurrence in EBOT (which was an invasive lesion). Endometrioid borderline ovarian tumors carry a good prognosis. Most EBOT tumors are stage I, therefore surgical staging is not necessary in most of the cases. However, uterine curettage is required in cases of uterine preservation. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. The value of dynamic contrast-enhanced MRI in characterizing complex ovarian tumors.

    Science.gov (United States)

    Li, Hai-Ming; Qiang, Jin-Wei; Ma, Feng-Hua; Zhao, Shu-Hui

    2017-01-14

    The study aimed to investigate the utility of dynamic contrast enhanced MRI (DCE-MRI) in the differentiation of malignant, borderline, and benign complex ovarian tumors. DCE-MRI data of 102 consecutive complex ovarian tumors (benign 15, borderline 16, and malignant 71), confirmed by surgery and histopathology, were analyzed retrospectively. The patterns (I, II, and III) of time-signal intensity curve (TIC) and three semi-quantitative parameters, including enhancement amplitude (EA), maximal slope (MS), and time of half rising (THR), were evaluated and compared among benign, borderline, and malignant ovarian tumors. The types of TIC were compared by Pearson Chi-square χ 2 between malignant and benign, borderline tumors. The mean values of EA, MS, and THR were compared using one-way ANOVA or nonparametric Kruskal-Wallis test. Fifty-nine of 71 (83%) malignant tumors showed a type-III TIC; 9 of 16 (56%) borderline tumors showed a type-II TIC, and 10 of 15 (67%) benign tumors showed a type-II TIC, with a statistically significant difference between malignant and benign tumors (P tumors (P tumors than in benign tumors and in borderline than in benign tumors (P tumors than in benign tumors and in borderline than in benign tumors (P tumors in MS and THR (P = 0.19, 0.153) or among malignant, borderline, and benign tumors in EA (all P > 0.05). DCE-MRI is helpful for characterizing complex ovarian tumors; however, semi-quantitative parameters perform poorly when distinguishing malignant from borderline tumors.

  18. Molecular Subtyping of Serous Ovarian Tumors Reveals Multiple Connections to Intrinsic Breast Cancer Subtypes

    DEFF Research Database (Denmark)

    Jönsson, Jenny-Maria; Johansson, Ida; Dominguez-Valentin, Mev

    2014-01-01

    OBJECTIVE: Transcriptional profiling of epithelial ovarian cancer has revealed molecular subtypes correlating to biological and clinical features. We aimed to determine gene expression differences between malignant, benign and borderline serous ovarian tumors, and investigate similarities...... with the well-established intrinsic molecular subtypes of breast cancer. METHODS: Global gene expression profiling using Illumina's HT12 Bead Arrays was applied to 59 fresh-frozen serous ovarian malignant, benign and borderline tumors. Nearest centroid classification was performed applying previously published...... expressed between benign and malignant serous ovarian tumors, with cell cycle processes enriched in the malignant subgroup. Borderline tumors were split between the two clusters. Significant correlations between the malignant serous tumors and the highly aggressive ovarian cancer signatures, and the basal...

  19. Insulin-Like Growth Factors (IGF) and IGF-Binding Proteins (IGFBP) in the Serum of Patients with Ovarian Tumors.

    Science.gov (United States)

    Gershtein, E S; Isaeva, E R; Kushlinsky, D N; Korotkova, E A; Ermilova, V D; Laktionov, K P; Adamyan, L V

    2016-04-01

    IGF-1, IGF-2, and IGFBP-1,2,3 were assayed in blood serum of patients with malignant ovarian tumors (n=44), borderline ovarian tumors (n=11), and benign ovarian tumors (n=12) as well as in healthy women (n=33). In blood serum of patients with malignant ovarian tumors, the level of IGF-1 was lower and IGFBP-1 was higher than in other groups. In patients with malignant and borderline ovarian tumors, the level of IGFBP-2 was higher than in healthy women and in patients with benign ovarian tumors. There was no correlation between most examined parameters and the clinical and morphological peculiarities of ovarian tumors. The study revealed IGF/IGFBP imbalance in patients with malignant ovarian tumor and showed that IGFBP-2 proved to be a potential diagnostic serological marker w with 90% sensitivity and 90% specificity.

  20. Prognostic indicators in ovarian serous borderline tumours.

    Science.gov (United States)

    Malpica, Anais; Longacre, Teri A

    2018-02-01

    There have been great strides in our understanding of the serous group of borderline and malignant pelvic epithelial neoplasms in the past decade. While most serous borderline tumours have a favourable prognosis, recurrences and progression to carcinoma occur, often following a protracted clinical course. Clinical and pathological risk factors tend to co-vary, but the presence and type of extraovarian disease is the most important predictor for progression. Progression usually takes the form of low-grade serous carcinoma, although transformation to high-grade carcinoma is occasionally seen. A serous borderline - low-grade serous carcinoma pathway analogous to neoplastic transformation pathways seen in other organ systems has been proposed, based on global gene expression profiling, shared mutations in KRAS or BRAF, and in most cases, the presence of serous borderline tumour in de novo low-grade serous carcinoma. This discussion focuses on the key prognostic factors that predispose to disease progression and/or transformation to carcinoma in serous borderline tumours. Published by Elsevier B.V.

  1. SATB2 Expression Distinguishes Ovarian Metastases of Colorectal and Appendiceal Origin From Primary Ovarian Tumors of Mucinous or Endometrioid Type.

    Science.gov (United States)

    Moh, Michelle; Krings, Gregor; Ates, Deniz; Aysal, Anil; Kim, Grace E; Rabban, Joseph T

    2016-03-01

    The primary origin of some ovarian mucinous tumors may be challenging to determine, because some metastases of extraovarian origin may exhibit gross, microscopic, and immunohistochemical features that are shared by some primary ovarian mucinous tumors. Metastases of primary colorectal, appendiceal, gastric, pancreatic, and endocervical adenocarcinomas may simulate primary ovarian mucinous cystadenoma, mucinous borderline tumor, or mucinous adenocarcinoma. Recently, immunohistochemical expression of SATB2, a transcriptional regulator involved in osteoblastic and neuronal differentiation, has been shown to be a highly sensitive marker of normal colorectal epithelium and of colorectal adenocarcinoma. SATB2 expression has not been reported in normal epithelium of the female reproductive tract. Therefore, we hypothesized that SATB2 may be of value in distinguishing ovarian metastases of colorectal adenocarcinoma from primary ovarian mucinous tumors and from primary ovarian endometrioid tumors. Among primary ovarian tumors, SATB2 staining was observed in 0/22 mucinous cystadenomas that lacked a component of mature teratoma, 4/12 mucinous cystadenomas with mature teratoma, 1/60 mucinous borderline tumors, 0/17 mucinous adenocarcinomas, 0/3 endometrioid borderline tumors, and 0/72 endometrioid adenocarcinomas. Among ovarian metastases, SATB2 staining was observed in 24/32 (75%) colorectal adenocarcinomas; 8/10 (80%) low-grade appendiceal mucinous neoplasms; and 4/4 (100%) high-grade appendiceal adenocarcinomas. No SATB2 staining was observed in any ovarian metastasis of pancreatic, gastric, gallbladder, or endocervical origin. Evaluation of primary extraovarian tumors showed the highest incidences of SATB2 staining among primary colorectal adenocarcinomas (71%), primary appendiceal low-grade mucinous neoplasms (100%), and primary appendiceal high-grade adenocarcinomas (100%). Similar to their metastatic counterparts, none of the primary pancreatic or gastric

  2. CT features of ovarian tumors

    International Nuclear Information System (INIS)

    Akiba, Ryuzo; Izumi, Sigeru; Tsutsui, Fumio; Kurihara, Soju; Hisa, Naofumi

    1985-01-01

    CT findings were compared with macroscopic and histopathologic findings in 84 patients with ovarian tumors. Marginal irregularity of the tumor shown on CT exhibited marked adhesion to the greater omentum, enteron or pelvic wall at laparotomy. CT showed tumor capsules more than 10 mm in thickness in 5 of 27 patients with malignant ovarian carcinomas (18.5%) and 2 of 15 patients with endometrioid cystadenoma (13.3%). Various thickness of the capsule was seen on CT in 48.1% of the patients with malignant ovarian carcinomas and 60.0% of the patients with endometrioid cystadenoma. Diagnostic accuracy of CT for the presence of absence of solid tumors was 89.3%. Misdiagnosis was attributed to the presence of high specific gravidity of fluid contents within the tumor, partial volume phenomenon, various thickness of the capsule, coagulation, and hair mass seen in dermoid cyst. Solid tumor-like density was larger and more irregular in the group with malignant ovarian tumors than in the group with benign ones. Irregular cystic parts were seen on CT in a high incidence among the group with malignant ovarian carcinomas. Dermoid cyst was diagnosed easily by CT because CT numbers were specific to the contents of cyst. (Namekawa, K.)

  3. Borderline Ovarian Tumors and Diagnostic Dilemma of Intraoperative Diagnosis: Could Preoperative He4 Assay and ROMA Score Assessment Increase the Frozen Section Accuracy? A Multicenter Case-Control Study

    Science.gov (United States)

    Gizzo, Salvatore; Berretta, Roberto; Di Gangi, Stefania; Guido, Maria; Zanni, Giuliano Carlo; Franceschetti, Ilaria; Quaranta, Michela; Plebani, Mario; Nardelli, Giovanni Battista; Patrelli, Tito Silvio

    2014-01-01

    The aim of our study was to assess the value of a preoperative He4-serum-assay and ROMA-score assessment in improving the accuracy of frozen section histology in the diagnosis of borderline ovarian tumors (BOT). 113 women presenting with a unilateral ovarian mass diagnosed as serous/mucinous BOT at frozen-section-histology (FS) and/or confirmed on final pathology were recruited. Pathologists were informed of the results of preoperative clinical/instrumental assessment of all patients. For Group_A patients, additional information regarding He4, CA125, and ROMA score was available (in Group_B only CA125 was known). The comparison between Group A and Group B in terms of FS accuracy, demonstrated a consensual diagnosis in 62.8% versus 58.6% (P: n.s.), underdiagnosis in 25.6% versus 41.4% (P < 0.05), and overdiagnosis in 11.6% versus 0% (P < 0.01). Low FS diagnostic accuracy was associated with menopausal status (OR: 2.13), laparoscopic approach (OR: 2.18), mucinous histotype (OR: 2.23), low grading (OR: 1.30), and FIGO stage I (OR: 2.53). Ultrasound detection of papillae (OR: 0.29), septa (OR: 0.39), atypical vascularization (OR: 0.34), serum He4 assay (OR: 0.39), and ROMA score assessment (OR: 0.44) decreased the probability of underdiagnosis. A combined preoperative assessment through serum markers and ultrasonographic features may potentially reduce the risk of underdiagnosis of BOTs on FS while likely increasing the concomitant incidence of false-positive events. PMID:25431767

  4. Borderline Ovarian Tumors and Diagnostic Dilemma of Intraoperative Diagnosis: Could Preoperative He4 Assay and ROMA Score Assessment Increase the Frozen Section Accuracy? A Multicenter Case-Control Study

    Directory of Open Access Journals (Sweden)

    Salvatore Gizzo

    2014-01-01

    Full Text Available The aim of our study was to assess the value of a preoperative He4-serum-assay and ROMA-score assessment in improving the accuracy of frozen section histology in the diagnosis of borderline ovarian tumors (BOT. 113 women presenting with a unilateral ovarian mass diagnosed as serous/mucinous BOT at frozen-section-histology (FS and/or confirmed on final pathology were recruited. Pathologists were informed of the results of preoperative clinical/instrumental assessment of all patients. For Group_A patients, additional information regarding He4, CA125, and ROMA score was available (in Group_B only CA125 was known. The comparison between Group A and Group B in terms of FS accuracy, demonstrated a consensual diagnosis in 62.8% versus 58.6% (P: n.s., underdiagnosis in 25.6% versus 41.4% (P<0.05, and overdiagnosis in 11.6% versus 0% (P<0.01. Low FS diagnostic accuracy was associated with menopausal status (OR: 2.13, laparoscopic approach (OR: 2.18, mucinous histotype (OR: 2.23, low grading (OR: 1.30, and FIGO stage I (OR: 2.53. Ultrasound detection of papillae (OR: 0.29, septa (OR: 0.39, atypical vascularization (OR: 0.34, serum He4 assay (OR: 0.39, and ROMA score assessment (OR: 0.44 decreased the probability of underdiagnosis. A combined preoperative assessment through serum markers and ultrasonographic features may potentially reduce the risk of underdiagnosis of BOTs on FS while likely increasing the concomitant incidence of false-positive events.

  5. Preoperative serum levels of epidermal growth factor receptor, HER2, and vascular endothelial growth factor in malignant and benign ovarian tumors

    DEFF Research Database (Denmark)

    Dahl Steffensen, Karina; Waldstrøm, Marianne; Jeppesen, Ulla

    2008-01-01

    , and malignant ovarian tumors. Patients and Methods: Serum from 233 patients (75 serous ovarian/tubal/peritoneal cancers, 24 borderline tumors, 110 benign ovarian tumors, and 24 with normal ovaries) were analyzed for EGFR, HER2, and VEGF using commercially available enzyme-linked immunosorbent assays (ELISA......). Results: The median EGFR serum level in patients with ovarian cancer was 51 ng/mL, and this was significantly lower than the median serum levels in borderline tumors (P =.0054) and benign ovarian tumors (P ... in patients with ovarian cancer was 10.2 ng/mL and not significantly different from any of the other patient groups. The median VEGF serum level in patients with ovarian cancer was 449 pg/mL and significantly higher than the levels found in borderline tumors (P =.021) and benign tumors (P =.0087) as well...

  6. Comparison of Plasma Osteopontin Levels between Patients with Borderline Ovarian Tumours and Serous Ovarian Carcinoma.

    Science.gov (United States)

    Živný, J H; Leahomschi, S; Klener, P; Živný, J; Haluzík, M; Cibula, D

    2016-01-01

    Osteopontin (OPN) is a novel biomarker of various cancers including ovarian carcinoma. OPN is a promising adjunct to a major biomarker of ovarian cancer, CA125, in diagnosis, differential diagnosis and prognosis. The aim of our study was to measure the plasma level of OPN and CA125 in patients with borderline ovarian tumours (BOTs), serous ovarian carcinoma, and controls to determine its potential role in the differential diagnosis between serous ovarian carcinoma and BOT. The plasma samples of 66 women were analysed using Luminex technology, designed to simultaneously measure multiple specific protein targets. The mean OPN plasma level for the control group was 23.3 ng/ml; for BOT 26.3 ng/ml; and for patients with serous ovarian carcinoma 59.5 ng/ml. Specifically, there was a significant difference between the OPN levels in patients with ovarian carcinoma and BOT (P ovarian carcinoma. The area under the ROC curve (AUC) for OPN was 0.793 (95% confidence interval (CI) 0.669-0.917, P ovarian carcinoma and BOT.

  7. Expression of FK506 binding protein 65 (FKBP65) is decreased in epithelial ovarian cancer cells compared to benign tumor cells and to ovarian epithelium

    DEFF Research Database (Denmark)

    Henriksen, Rudi; Sørensen, Flemming Brandt; Ørntoft, Torben Falck

    2011-01-01

    to be followed by a strongly increased risk of ovarian cysts. We performed the present study to reveal how FKBP65 is expressed in the ovary and in ovarian tumors and to see if this expression might be related to ovarian tumor development, a relationship we have found in colorectal cancer. Biopsies from...... prospectively collected samples from ovaries and benign, borderline, and invasive ovarian tumors were analyzed for expression of FKBP65 by immunohistochemistry. The expression was compared to survival and several clinicopathological parameters. FKBP65 is strongly expressed in ovarian epithelium and in benign...

  8. Determination of BRAF V600E (VE1) protein expression and BRAF gene mutation status in codon 600 in borderline and low-grade ovarian cancers.

    Science.gov (United States)

    Sadlecki, Pawel; Walentowicz, Pawel; Bodnar, Magdalena; Marszalek, Andrzej; Grabiec, Marek; Walentowicz-Sadlecka, Malgorzata

    2017-05-01

    Epithelial ovarian tumors are a group of morphologically and genetically heterogeneous neoplasms. Based on differences in clinical phenotype and genetic background, ovarian neoplasms are classified as low-grade and high-grade tumor. Borderline ovarian tumors represent approximately 10%-20% of all epithelial ovarian masses. Various histological subtypes of ovarian malignancies differ in terms of their risk factor profiles, precursor lesions, clinical course, patterns of spread, molecular genetics, response to conventional chemotherapy, and prognosis. The most frequent genetic aberrations found in low-grade serous ovarian carcinomas and serous borderline tumors, as well as in mucinous cancers, are mutations in BRAF and KRAS genes. The most commonly observed BRAF mutation is substitution of glutamic acid for valine in codon 600 (V600E) in exon 15. The primary aim of this study was to determine whether fully integrated, real-time polymerase chain reaction-based Idylla™ system may be useful in determination of BRAF gene mutation status in codon 600 in patients with borderline ovarian tumors and low-grade ovarian carcinomas. The study included tissue specimens from 42 patients with histopathologically verified ovarian masses, who were operated on at the Department of Obstetrics and Gynecology, Nicolaus Copernicus University Collegium Medicum in Bydgoszcz (Poland). Based on histopathological examination of surgical specimens, 35 lesions were classified as low-grade ovarian carcinomas, and 7 as borderline ovarian tumors. Specimens with expression of BRAF V600E (VE1) protein were tested for mutations in codon 600 of the BRAF gene, using an automated molecular diagnostics platform Idylla™. Cytoplasmic immunoexpression of BRAF V600E (VE1) protein was found in three specimens: serous superficial papilloma, serous papillary cystadenoma of borderline malignancy, and partially proliferative serous cystadenoma. All specimens with the expression of BRAF V600E (VE1) protein were

  9. Plasma fibrinogen levels in patients with benign and malignant ovarian tumors.

    Science.gov (United States)

    Hefler-Frischmuth, Katrin; Lafleur, Judith; Hefler, Lukas; Polterauer, Stephan; Seebacher, Veronika; Reinthaller, Alexander; Grimm, Christoph

    2015-03-01

    Plasma fibrinogen is a key acute phase protein and known to be elevated in ovarian cancer. We aimed to investigate the association between plasma fibrinogen and malignant and benign ovarian tumors. In a retrospective, single-center study, we evaluated preoperative plasma fibrinogen levels in 471 patients with benign and in 224 patients with malignant (borderline ovarian tumor [BOT]: n=36, epithelial ovarian cancer [EOC]: n=188) ovarian tumors. The association between preoperative plasma fibrinogen levels and clinico-pathological parameters was investigated. A multivariate logistic regression model was performed to identify an independent association. Mean (standard deviation) preoperative plasma fibrinogen levels in patients with benign ovarian tumors, BOT, and invasive ovarian cancers were 346.7 (99.7), 372.8 (114), and 472.6 (148.4) mg/dL, respectively (povarian tumors in CA 125 positive and negative patients. Plasma fibrinogen levels are independently associated with malignant ovarian tumors. Plasma fibrinogen levels showed an independent association with malignant ovarian tumors in the subgroup of patients ovarian tumors is particularly challenging. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. BRAF mutational analysis in ovarian tumors: recent perspectives

    Directory of Open Access Journals (Sweden)

    Wong KK

    2015-09-01

    Full Text Available Kwong-Kwok Wong,1 Ching-Chou Tsai,2 David M Gershenson11Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 2Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan, Republic of ChinaAbstract: BRAF mutations are rare in ovarian cancer and mainly occur in indolent serous borderline tumors (SBTs, also known as serous tumors of low malignant potential or atypical proliferative serous tumors. The reported percentage of BRAF mutations in SBTs varies from 23% to 71%. Although a high percentage of stage II–IV SBTs with noninvasive implants have progressed to invasive low-grade serous carcinomas when patients were observed for 5 years or longer, BRAF mutations are rare in low-grade serous carcinomas as well as in invasive implants associated with SBTs. BRAF mutations in SBTs may prevent SBTs from progressing to invasive carcinomas. On the other hand, the reported percentage of BRAF mutations in mucinous carcinoma (20% is much higher than that of mucinous borderline tumor (5%. Further investigation of the role of BRAF mutations in SBTs and mucinous tumor will shed light on the molecular mechanism underlying the role of BRAF mutations in tumor progression in different cellular context and the clinical utility of BRAF mutations in SBTs as a biomarker of favorable prognosis.Keywords: BRAF V600E, ovarian cancer, COLD-PCR

  11. Evaluation of p53, PTEN and β-catenin Immunoexpressions in Primary Ovarian Epithelial Tumors

    Directory of Open Access Journals (Sweden)

    Fatemeh Sari Aslani

    2015-07-01

    Full Text Available Background: Ovarian cancer comprises a heterogeneous group of neoplasms. The prognosis cannot be predicted by histopathologic examination alone. The aim of this study is to evaluate p53, PTEN, and β-catenin expressions in primary ovarian carcinomas in an attempt to find a possible relationship with morphologic parameters and clinical findings. Methods: The study included 100 epithelial ovarian tumors (borderline and carcinomas from affiliated hospitals of Shiraz university of medical sciences during 2007-2013. Immunohistochemical staining for p53, PTEN, and β-catenin was performed on 65 serous, 18 mucinous, 10 endometrioid, 5 clear cell, and 2 mixed tumors. Results: p53 expression pattern in serous carcinoma significantly differed from endometrioid carcinomas. Strong positivity (2+ in >50% of the tumor cells favored serous carcinoma. PTEN expression significantly differed in mucinous and serous carcinomas as well as in endometrioid carcinoma and borderline endometrioid tumor. There was significantly decreased β-catenin expression in the carcinomas compared with borderline tumors. In all of the different subtypes of ovarian carcinomas, we observed a significant association with decreased β-catenin expression to tumor grade as well as in serous carcinomas with increased nuclear grade, mitosis, and tumor grade. There was no significant relation between expressions of p53, PTEN, and β-catenin in epithelial ovarian tumors to FIGO staging, response to chemotherapy, serum CA- 125 marker, and tumor recurrence. Conclusion: p53 and PTEN are helpful in differentiation of some epithelial ovarian tumor subtypes. In serous carcinomas, diminished expression of β-catenin is associated with higher tumor and nuclear grade. This expression is significantly different in borderline and carcinomas.

  12. Early inflammatory response in epithelial ovarian tumor cyst fluids

    International Nuclear Information System (INIS)

    Kristjánsdóttir, Björg; Partheen, Karolina; Fung, Eric T; Yip, Christine; Levan, Kristina; Sundfeldt, Karin

    2014-01-01

    Mortality rates for epithelial ovarian cancer (EOC) are high, mainly due to late-stage diagnosis. The identification of biomarkers for this cancer could contribute to earlier diagnosis and increased survival rates. Given that chronic inflammation plays a central role in cancer initiation and progression, we selected and tested 15 cancer-related cytokines and growth factors in 38 ovarian cyst fluid samples. We used ovarian cyst fluid since it is found in proximity to the pathology and mined it for inflammatory biomarkers suitable for early detection of EOC. Immunoprecipitation and high-throughput sample fractionation were obtained by using tandem antibody libraries bead and mass spectrometry. Two proteins, monocyte chemoattractant protein-1 (MCP-1/CCL2) and interleucin-8 (IL-8/CXCL8), were significantly (P < 0.0001) higher in the malignant (n = 16) versus benign (n = 22) tumor cysts. Validation of MCP-1, IL-8, and growth-regulated protein-α (GROα/CXCL1) was performed with ELISA in benign, borderline, and malignant cyst fluids (n = 256) and corresponding serum (n = 256). CA125 was measured in serum from all patients and used in the algorithms performed. MCP-1, IL-8, and GROα are proinflammatory cytokines and promoters of tumor growth. From 5- to 100-fold higher concentrations of MCP-1, IL-8 and GROα were detected in the cyst fluids compared to the serum. Significant (P < 0.001) cytokine response was already established in borderline cyst fluids and stage I EOC. In serum a significant (P < 0.01) increase of IL-8 and GROα was found, but not until stage I and stage III EOC, respectively. These findings confirm that early events in tumorigenesis can be analyzed and detected in the tumor environment and we conclude that ovarian cyst fluid is a promising source in the search for new biomarkers for early ovarian tumors

  13. [Serous and mucinous epithelial ovarian tumors--a clinicopathologic study of 116 cases].

    Science.gov (United States)

    Giurgea, Nicoleta Luminiţa; Pitrop, Mariana; Mihailovici, Maria Sultana

    2012-01-01

    Surface epithelial tumors are the most important group of neoplasm of the ovary. These tumors are classified according to the following parameters: cell type, pattern of growth, amount of fibrous stroma, atypia and invasiveness. This study aimed to identify ovarian tumours, especially borderline type, by applying last parameters of criteria for histologic diagnostic of ovarian neoplasms. The retrospective study included 116 patients with ovarian tumors diagnosed, investigated, surgically treated at the Obstetrical and Gynecological Hospital Botoşani in the past 9 years (2002-2010). In this interval were recorded 116 cases of epithelial ovarian tumors. In sample processing, we used formalin for fixation, paraffin for specimen embedding and hematoxilin-eosin for staining. The age of the patients ranged between 19-86 years. From 116 cases, 57 (49,1%) were benign, 40 (34,5%) malignant and 19 (16,4%) borderline. In our study of benign neoplasms, we included 37 cases of serous tumours (64,9%) and 20 cases of mucinous types (35%). In the group of borderline tumours, the serous type was the most frequent (13 cases), followed by mucinous types (6), including 5 cases of intestinal type and 1 of endocervical pattern. The malignant tumors, according with decreasing order of frequency, were the following: 19 serous (47,5%), 8 mucinous (20%), 11 endometroid type (27,5%) and one of each cases of clear cell and small cell tumors (2,5%). Of great interest in our research was to identify ovarian borderline tumours, still representing a controversial group, in the same time corresponding with a scientiphic progress. Because the spectrum of epithelial tumors is very large, extensive sampling is essential to carry out all these important determinations, because benign, borderline and malignant patterns can be found in the same tumor.

  14. Pathology-oriented treatment strategy of malignant ovarian tumor in pregnant women: analysis of 41 cases in Japan.

    Science.gov (United States)

    Morikawa, Asuka; Ueda, Kazu; Takahashi, Kazuaki; Fukunaga, Masaharu; Iwashita, Mitsutoshi; Kobayashi, Yoichi; Takechi, Kimihiro; Umezawa, Satoshi; Terauchi, Fumitoshi; Kiguchi, Kazushige; Aoki, Daisuke; Nomura, Hiroyuki; Yoshikawa, Hiroyuki; Satoh, Toyomi; Jobo, Toshiko; Fujiwara, Hiroyuki; Takei, Yuji; Kamoi, Seiryu; Terao, Yasuhisa; Isonishi, Seiji

    2014-12-01

    The aim of this study was to investigate the impact of the histological findings on the treatment of malignant ovarian tumors in pregnant women. This is a retrospective study of 41 patients diagnosed and treated for ovarian malignancy during pregnancy between 1985 and 2010. The median age of the study group was 30 years old, ranging from 20 to 41. Thirty-eight (92 %) patients were diagnosed with stage I, and one (2 %) with each of stages II, III, and IV. Twenty-five (61 %) patients had borderline malignancy, 8 (20 %) were diagnosed with epithelial ovarian cancer, 7 (17 %) with germ cell tumor, and one with sex cord stromal tumor. All patients received primary surgery; 7 (17 %) patients had cystectomy, 32 (78 %) had unilateral salpingo-oophorectomy, and 3 (7 %) underwent hysterectomy with bilateral salpingo-oophorectomy. Thirty-one (76 %) patients delivered live newborns; 21 had borderline tumor (84 %), 2 had ovarian cancers (25 %), and 8 had non-epithelial tumor (100 %). Six cases were terminated in order to perform the standard treatment for ovarian malignancy and 2 cases aborted spontaneously. In pregnant women, ovarian cancer is exceptionally less frequent compared with non-pregnant women, i.e. age-matched, statistically-corrected controls based on the Japanese annual report [8/33 (24 %) vs. control (60 %); ovarian cancer/(ovarian cancer + borderline tumor), P = 0.001]. The pregnant women with ovarian cancer chose to prioritize treatment of ovarian cancer at the sacrifice of their babies while those with borderline tumor or non-epithelial tumor were able to successfully deliver live newborns.

  15. Risk of Local Recurrence of Benign and Borderline Phyllodes Tumors

    DEFF Research Database (Denmark)

    Borhani-Khomani, Kaveh; Talman, Maj-Lis Møller; Kroman, Niels

    2016-01-01

    PURPOSE: To determine the recurrence rate of benign and borderline phyllodes tumors (PTs) of the breast, the association between the size of resection margin and risk of recurrence and the risk of progression of histological grading at recurrence. METHODS: Nationwide retrospective study on Danish...... in histological grading was found. The results do not justify wide excision margins of nonmalignant phyllodes tumors of the breast....... women aged 18 years or older, operated from 1999 to 2014, with resected benign or borderline PTs. Information on age, size of primary tumor and recurrence, histological grade, surgical treatment, margin size, and local recurrence were collected from the national Danish Pathology Register. RESULTS...

  16. Spectrum of fluorodeoxyglucose-positron emission tomography/computed tomography and magnetic resonance imaging findings of ovarian tumors.

    Science.gov (United States)

    Kitajima, Kazuhiro; Ueno, Yoshiko; Maeda, Tetsuo; Murakami, Koji; Kaji, Yasushi; Kita, Masato; Suzuki, Kayo; Sugimura, Kazuro

    2011-11-01

    The purpose of this article is to review fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) and magnetic resonance imaging (MRI) findings in a variety of benign, malignant, and borderline malignant ovarian tumors. It is advantageous to become familiar with the wide variety of FDG-PET/CT findings of this entity. Benign ovarian tumors generally have faint uptake, whereas endometriomas, fibromas, and teratomas show mild to moderate uptake. Malignant ovarian tumors generally have intense uptake, whereas tumors with a small solid component often show minimal uptake.

  17. Novel Treatment Shrinks Ovarian Tumors in Mice

    Science.gov (United States)

    Researchers have developed a new approach for treating tumors that express mutant versions of the p53 protein, which are present in more than half of all cancers, including an aggressive and common subtype of ovarian cancer.

  18. Sox10 expression in ovarian epithelial tumors is associated with poor overall survival.

    Science.gov (United States)

    Kwon, Ah-Young; Heo, Ilyeong; Lee, Hye Jin; Kim, Gwangil; Kang, Haeyoun; Heo, Jin-Hyung; Kim, Tae Hoen; An, Hee Jung

    2016-05-01

    Sox10 is a transcription factor regulating the development of several cell lineages and is involved in tumor development. However, the clinicopathological relevance of Sox10 expression in ovarian cancer has not been examined. We assessed expression of Sox10 in ovarian epithelial tumors by immunohistochemistry and assessed its prognostic value by analyzing the correlation between its expression and clinicopathological factors. We used tissue microarrays including 244 ovarian epithelial tumors. Sox10 staining was found in the cytoplasm or nucleus of tumor cells. Malignant serous, mucinous, and endometrioid tumors were significantly more likely to express Sox10 than benign and borderline tumors. Expression patterns in adenocarcinomas were different for histologic subtypes: nuclear Sox10 staining was common in clear-cell adenocarcinomas and serous adenocarcinomas, whereas all cases of mucinous and endometrioid tumors were negative for nuclear staining. Nuclear Sox10 staining was also associated with chemoresistance and shorter overall survival in ovarian adenocarcinomas, notably in high-grade serous adenocarcinoma. Sox10 is expressed in many ovarian carcinomas, suggesting that it might be involved in oncogenesis of ovarian carcinoma. Expression pattern of Sox10 differs between histological subtypes. Nuclear Sox10 expression is an independent indicator of poor prognosis in ovarian adenocarcinomas, notably in high-grade serous adenocarcinomas.

  19. Long-term Behavior of Serous Borderline Tumors Subdivided Into Atypical Proliferative Tumors and Noninvasive Low-grade Carcinomas

    DEFF Research Database (Denmark)

    Vang, Russell; Hannibal, Charlotte G; Junge, Jette

    2017-01-01

    Ovarian serous borderline tumors (SBTs) have been the subject of considerable controversy, particularly with regard to terminology and behavior. It has been proposed that they constitute a heterogenous group of tumors composed, for the most part, of typical SBTs that are benign and designated...... "atypical proliferative serous tumor (APST)" and a small subset of SBTs with micropapillary architecture that have a poor outcome and are designated "noninvasive low-grade serous carcinoma (niLGSC)". It also has been argued that the difference in behavior between the 2 groups is not due to the subtype...... renamed "low-grade serous carcinoma" (LGSC). The argument as to whether it is the appearance of the primary tumor or the presence of extraovarian LGSC that determines outcome remains unsettled. The current study was initiated in 2004 and was designed to determine what factors were predictive of outcome...

  20. Utility of DWI with quantitative ADC values in ovarian tumors: a meta-analysis of diagnostic test performance.

    Science.gov (United States)

    Pi, Shan; Cao, Rong; Qiang, Jin Wei; Guo, Yan Hui

    2018-01-01

    Background Diffusion-weighted imaging (DWI) and quantitative apparent diffusion coefficient (ADC) values are widely used in the differential diagnosis of ovarian tumors. Purpose To assess the diagnostic performance of quantitative ADC values in ovarian tumors. Material and Methods PubMed, Embase, the Cochrane Library, and local databases were searched for studies assessing ovarian tumors using quantitative ADC values. We quantitatively analyzed the diagnostic performances for two clinical problems: benign vs. malignant tumors and borderline vs. malignant tumors. We evaluated diagnostic performances by the pooled sensitivity and specificity values and by summary receiver operating characteristic (SROC) curves. Subgroup analyses were used to analyze study heterogeneity. Results From the 742 studies identified in the search results, 16 studies met our inclusion criteria. A total of ten studies evaluated malignant vs. benign ovarian tumors and six studies assessed malignant vs. borderline ovarian tumors. Regarding the diagnostic accuracy of quantitative ADC values for distinguishing between malignant and benign ovarian tumors, the pooled sensitivity and specificity values were 0.91 and 0.91, respectively. The area under the SROC curve (AUC) was 0.96. For differentiating borderline from malignant tumors, the pooled sensitivity and specificity values were 0.89 and 0.79, and the AUC was 0.91. The methodological quality of the included studies was moderate. Conclusion Quantitative ADC values could serve as useful preoperative markers for predicting the nature of ovarian tumors. Nevertheless, prospective trials focused on standardized imaging parameters are needed to evaluate the clinical value of quantitative ADC values in ovarian tumors.

  1. [Association of ovarian tumors with CA-125].

    Science.gov (United States)

    Martínez-Acosta, Judith Elena; Olguín-Cruces, Víctor Alberto

    2016-01-01

    The tumor marker CA-125 is the most widely used serum marker for ovarian cancer screening. The aim of this paper was to establish the association between histopathologic result of ovarian tumors with serologic CA-125 and utility for the diagnosis of ovarian tumors at a Ginecoobstetric hospital. An observational, retrospective, descriptive and longitudinal study, from September 1st 2010 to February 28 2013. All patients with histopathologic report ovarian tumor and CA-125 was selected to analyze the association of ovarian tumors with their histological type, biological behavior, range positivity of CA-125 and its relationship to the pre and postmenopausal state. Of 1213 patients, 334 were included. Utility of CA-125 in postmenopausal reported positive predictive value of 67.5%, with sensitivity (72%), specificity (82.6%) and negative predictive value (86.1%), both with p = 0.001, mainly in the epithelial origin. In premenopausal a low positive predictive value was reported. The CA-125 is useful for screening for ovarian cancer in postmenopausal women, mainly for epithelial origin.

  2. Comparing the Copenhagen Index (CPH-I) and Risk of Ovarian Malignancy Algorithm (ROMA): Two equivalent ways to differentiate malignant from benign ovarian tumors before surgery?

    Science.gov (United States)

    Yoshida, Adriana; Derchain, Sophie Françoise; Pitta, Denise Rocha; Andrade, Liliana Aparecida Lucci De Angelo; Sarian, Luis Otavio

    2016-03-01

    To evaluate the prediction of malignancy in women with pelvic masses using the Copenhagen Index (CPH-I) and Risk of Ovarian Malignancy Algorithm (ROMA). Three hundred eighty four women operated due to an ovarian mass were enrolled between January 2010 and June 2015. All patients had histopathological diagnosis, HE4 and CA125 measurement. CPH-I and ROMA were calculated and their performances compared in two distinct scenarios: 1) for the discrimination of benign ovarian disease from epithelial ovarian cancer (EOC), non-epithelial ovarian cancer, borderline ovarian tumors (BOT) and ovarian metastases, and 2) for the discrimination of benign disease from EOC. Receiver Operator Characteristics' Areas Under the Curves (AUC) were calculated for CPH-I and ROMA and compared. Of the 384 women, 224 presented a benign ovarian tumor, 32 BOT, 87 EOC, 26 non-epithelial ovarian cancer, and 15 had ovarian metastases. The best AUCs were obtained for the discrimination of EOC from benign tumors. CPH-I performed slightly better than ROMA, and both approached 89% sensitivity and 85% specificity. When all malignant tumors (EOC, BOT, ovarian metastases and non-epithelial ovarian cancer - entire cohort) were included, the performance of CPH-I and ROMA declined to nearly 72%, although the specificity remained close to 85%. CPH-I and ROMA performed similarly well for the discrimination of EOC from benign ovarian tumors. However, caution is necessary since, in practical situations, where all the histological possibilities for malignant ovarian tumors must be considered, the sensitivity of CPH-I and ROMA may not surpass 70%. Copyright © 2016. Published by Elsevier Inc.

  3. A Borderline Ovarian Tumour in a Patient with Classic Bladder Exstrophy; a Case Report.

    LENUS (Irish Health Repository)

    Beauchamp, K

    2018-02-01

    A 37-year-old Romanian lady presented with a large pelvic mass, urosepsis and deteriorating renal function. She had undergone separation from her conjoined twin. Imaging revealed grossly abnormal anatomy and a suspicious pelvic mass. Examination was consistent with classic bladder exstrophy. Postoperative histology showed borderline ovarian tumour (BTO)

  4. Prevalence of Appendiceal Lesions in Appendicectomies Performed During Surgery for Mucinous Ovarian Tumors: A Retrospective Study.

    Science.gov (United States)

    Moore, Luiza; Gajjar, Ketan; Jimenez-Linan, Mercedes; Crawford, Robin

    2016-10-01

    The aim of this study was to assess the frequency of appendiceal pathology in women undergoing surgery for mucinous ovarian neoplasm and to evaluate whether appendicectomy is necessary. This single-institution retrospective study reviewed prevalence of appendiceal lesions in all patients operated on at our institution from 2002 to 2013 with the final diagnosis of mucinous tumor of the ovary. Clinicopathological data were analyzed. One hundred twenty-three cases were identified. These included 45 (37%) benign mucinous ovarian neoplasms, 63 (51%) borderline, and 11 (9%) invasive mucinous ovarian tumors. In addition, 4 (3%) cases of metastatic tumors to the ovary were also identified. Appendiceal pathology was found in association with all types of mucinous ovarian tumors (benign, borderline, and malignant). In 24% of cases, appendix was macroscopically abnormal at the time of the surgery, prompting the surgical removal. Regardless of the gross findings, microscopic abnormality in the appendix was seen in 24% of all cases. The prevalence of significant occult microscopic appendiceal pathology, that is, when the appendix was grossly normal, was 6%. Given the prevalence of coexisting appendiceal pathology found in this study and the reported low rates of complications associated with the procedure, an appendicectomy is recommended in the management of all mucinous ovarian neoplasms.

  5. Extremely rare borderline phyllodes tumor in the male breast: a case report.

    Science.gov (United States)

    Kim, Jung Gyu; Kim, Shin Young; Jung, Hae Yoen; Lee, Deuk Young; Lee, Jong Eun

    2015-01-01

    Phyllodes tumor of the male breast is an extremely rare disease, and far fewer cases of borderline phyllodes tumors than benign or malignant tumors in the male breast have been reported. We report a case of borderline phyllodes tumor in the male breast with imaging findings of the tumor and pathologic correlation. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. MRI for discriminating metastatic ovarian tumors from primary epithelial ovarian cancers

    OpenAIRE

    Xu, Yanhong; Yang, Jia; Zhang, Zaixian; Zhang, Guixiang

    2015-01-01

    Aims To find specific magnetic resonance imaging (MRI) features to differentiate metastatic ovarian tumors from primary epithelial ovarian cancers. Methods Eleven cases with metastatic ovarian tumors and 26 cases with primary malignant epithelial ovarian cancers were retrospectively studied. All features such as patient characteristics, MRI findings and biomarkers were evaluated. The differences including laterality, configuration, uniformity of locules, diffusion weighted imaging (DWI) signa...

  7. Optical biomarkers of serous and mucinous human ovarian tumor assessed with nonlinear optics microscopies.

    Science.gov (United States)

    Adur, Javier; Pelegati, Vitor B; de Thomaz, Andre A; Baratti, Mariana O; Almeida, Diogo B; Andrade, L A L A; Bottcher-Luiz, Fátima; Carvalho, Hernandes F; Cesar, Carlos L

    2012-01-01

    Nonlinear optical (NLO) microscopy techniques have potential to improve the early detection of epithelial ovarian cancer. In this study we showed that multimodal NLO microscopies, including two-photon excitation fluorescence (TPEF), second-harmonic generation (SHG), third-harmonic generation (THG) and fluorescence lifetime imaging microscopy (FLIM) can detect morphological and metabolic changes associated with ovarian cancer progression. We obtained strong TPEF + SHG + THG signals from fixed samples stained with Hematoxylin & Eosin (H&E) and robust FLIM signal from fixed unstained samples. Particularly, we imaged 34 ovarian biopsies from different patients (median age, 49 years) including 5 normal ovarian tissue, 18 serous tumors and 11 mucinous tumors with the multimodal NLO platform developed in our laboratory. We have been able to distinguish adenomas, borderline, and adenocarcinomas specimens. Using a complete set of scoring methods we found significant differences in the content, distribution and organization of collagen fibrils in the stroma as well as in the morphology and fluorescence lifetime from epithelial ovarian cells. NLO microscopes provide complementary information about tissue microstructure, showing distinctive patterns for serous and mucinous ovarian tumors. The results provide a basis to interpret future NLO images of ovarian tissue and lay the foundation for future in vivo optical evaluation of premature ovarian lesions.

  8. Optical biomarkers of serous and mucinous human ovarian tumor assessed with nonlinear optics microscopies.

    Directory of Open Access Journals (Sweden)

    Javier Adur

    Full Text Available Nonlinear optical (NLO microscopy techniques have potential to improve the early detection of epithelial ovarian cancer. In this study we showed that multimodal NLO microscopies, including two-photon excitation fluorescence (TPEF, second-harmonic generation (SHG, third-harmonic generation (THG and fluorescence lifetime imaging microscopy (FLIM can detect morphological and metabolic changes associated with ovarian cancer progression.We obtained strong TPEF + SHG + THG signals from fixed samples stained with Hematoxylin & Eosin (H&E and robust FLIM signal from fixed unstained samples. Particularly, we imaged 34 ovarian biopsies from different patients (median age, 49 years including 5 normal ovarian tissue, 18 serous tumors and 11 mucinous tumors with the multimodal NLO platform developed in our laboratory. We have been able to distinguish adenomas, borderline, and adenocarcinomas specimens. Using a complete set of scoring methods we found significant differences in the content, distribution and organization of collagen fibrils in the stroma as well as in the morphology and fluorescence lifetime from epithelial ovarian cells.NLO microscopes provide complementary information about tissue microstructure, showing distinctive patterns for serous and mucinous ovarian tumors. The results provide a basis to interpret future NLO images of ovarian tissue and lay the foundation for future in vivo optical evaluation of premature ovarian lesions.

  9. Protein levels and gene expressions of the epidermal growth factor receptors, HER1, HER2, HER3 and HER4 in benign and malignant ovarian tumors

    DEFF Research Database (Denmark)

    Dahl Steffensen, Karina; Waldstrøm, Marianne; Fredslund Andersen, Rikke

    2008-01-01

    , but this is not elucidated in detail in ovarian tissue. High tumor-to-normal-tissue concentration ratios would be favorable for molecular targeted anti-cancer treatment. The primary aim of the study was to analyze the potential differential protein content and gene expression of the four receptors in benign and malignant...... ovarian tumors. Tissue from 207 patients (101 malignant, 19 borderline, 64 benign ovarian tumors and 23 normal ovaries) were analyzed by quantitative ELISA for HER1-HER4 protein concentrations and by real-time PCR for HER1-HER4 gene expression. HER2 was also analyzed by immunohistochemistry. The HER2......-4 receptor protein content and the median gene expression level was significantly higher in ovarian cancer patients compared to patients with benign ovarian tumors and normal ovaries (povarian cancer compared to borderline...

  10. Ovarian Sex Cord-Stromal Tumors.

    Science.gov (United States)

    Schultz, Kris Ann P; Harris, Anne K; Schneider, Dominik T; Young, Robert H; Brown, Jubilee; Gershenson, David M; Dehner, Louis P; Hill, D Ashley; Messinger, Yoav H; Frazier, A Lindsay

    2016-10-01

    Ovarian sex cord-stromal tumors are clinically significant heterogeneous tumors that include several pathologic types. These tumors are often found in adolescents and young adults and can present with hormonal manifestations as well as signs and symptoms of a pelvic mass. Serum tumor markers may assist in preoperative diagnosis and surveillance. Several subtypes are associated with genetic predisposition, including those observed in patients with Peutz-Jegher syndrome. Recent studies have elucidated the relationship between Sertoli-Leydig cell tumors and DICER1 mutations. When classified as International Federation of Gynecology and Obstetrics stage Ia, most subtypes may be treated with surgery alone. Higher stage or recurrent tumors have variable prognoses that range from a usually rapid course in poorly differentiated Sertoli-Leydig cell tumor to an often prolonged course in adult granulosa cell tumors. New understanding of the molecular pathogenesis of these tumors may pave the way for novel therapeutics.

  11. [Expression and significance of Survivin and Smac in ovarian mucinous tumors].

    Science.gov (United States)

    Wang, Hong-xia; Chen, Gang; Li, Guo-li; Jiang, Ya-jun

    2010-06-01

    To investigate the expressions and significances of Survivin and Smac in ovarian mucinous tumors. A total of 55 paraffin-embedded specimens of primary ovarian mucinous tumors were collected. SABC was used to detect protein expression of Survivin and Smac genes. Immunoelectron microscopy using colloidal gold labeling was performed to determine the subcellular localization and patterns of Smac protein expression. (1) The cytoplasmic expression rates of survivin in benign, borderline and malignant ovarian mucinous tumors were 2/20, 12/15 and 20/20 respectively, which presents an improving trend.There were significant differences of survivin expression between benign vs. borderline lesions (P Smac among the three groups were 19/20, 9/15 and 3/20, respectively. There was significant difference among the three groups (P Smac (r = -0.153, P Smac granules in the three groups were 24.1 ± 7.2, 11.1 ± 1.9 and 5.2 ± 1.7, respectively, and there were significant differences among the three groups (P Smac granules were 4.7 ± 3.0, 2.9 ± 1.0 and 1.7 ± 1.3, although without significant difference among the three groups (P > 0.05). With the malignant development of ovarian mucinous tumors, the expressions of Survivin are up-regulated, and the expressions of Smac are down-regulated. Smac proteins exist mainly in an inactive intramembranous storage form inside of mitochondria.

  12. [The morphological and immunohistochemical characteristics of changes in the fallopian tube mucosa in ovarian epithelial tumors].

    Science.gov (United States)

    Asaturova, A V; Ezhova, L S; Faizullina, N M; Sannikova, M V; Khabas, G N

    2016-01-01

    to study the incidence of fallopian tube lesions (secretory cell proliferations (SCP), p53 signature, serous tubal intraepithelial lesions (STIL), and serous tubal intraepithelial carcinomas (STIC) in ovarian epithelial tumors and to propose their pathogenetic association with a certain histotype of the ovarian tumor. The investigation enrolled 136 patients with ovarian epithelial tumors, whose fallopian tubes were morphologically and immunohistochemically (IHC) examined using p53, Ki-67, and PAX2. Statistical analysis was carried out applying the Mann-Whitney test and χ(2) test. Lesions meeting the STIC criteria were found in 14.7% of cases (only in ovarian serous carcinoma (OSC)), those suspecting STICs were in 25.7%, and those without signs of STICs were in 59.6%. IFC examination diagnosed STIC in 10% of cases (only in OSC), STIL in 13.3%, p53 signature in 11.7% (only in serous tumors), and the normal/reactively changed tubal epithelium in 65%. The incidence of STILs correlated with the malignant potential of serous tumors significantly (pSTIC and high-grade OSC and revealed significant differences in the incidence of other fallopian tubal intraepithelial lesions in serous cystadenomas, borderline tumors, and OSC, in different ovarian carcinomas. The findings may suggest that the earliest stage in the pathogenesis of OSC is the development of SCP, followed by the formation of p53 signatures that may further give rise to STIL, and finally STC (due to the acquisition of additional mutations).

  13. Risk for borderline ovarian tumours after exposure to fertility drugs

    DEFF Research Database (Denmark)

    Bjørnholt, Sarah Marie; Kjaer, Susanne Krüger; Nielsen, Thor Schütt Svane

    2015-01-01

    tumours was observed after the use of progesterone. WHAT IS KNOWN ALREADY: Many epidemiological studies have addressed the connection between fertility drugs use and risk for ovarian cancer; most have found no strong association. Fewer studies have assessed the association between use of fertility drugs...

  14. Radiologic findings of malignant tumors arising from ovarian endometriosis

    International Nuclear Information System (INIS)

    Lee, Eun Ju; Joo, Hee Jae; Kim, Bo Hyun

    1999-01-01

    To determine the radiologic characteristics of malignant tumors arising from ovarian endometriosis. The radiologic findings of eleven patients with pelvic masses histologically confirmed as malignant ovarian tumors arising from endometriosis were retrospectively reviewed. All patients underwent MR, and six underwent ultrasonography. The findings were evaluated with regard to tumor size and shape, locularity, thickness and enhancement of the wall and septa, the presence of papillary nodule or solid portion, signal intensity of the locule, the presence of mass in contralateral ovary, ascites, local invasion, distant metastases, and the Pathologic diagnosis included clear cell carcinoma in six cases, endometrioid carcinoma in three, and mucinous cystadenocarcinoma of borderline malignancy and endometrial stromal sarcoma in one case each. Tumor size ranged from 8 to 20 (mean, 12.7)cm. The tumors were mixed in four cases, entirely cystic in three, predominantly cystic in three, and predominantly solid in one. Six cases were unilocular and five were multilocular. The wall and septa varied in thickness and regularity and were well enhanced in all but one case. In all cases papillary nodules or solid portions with similar enhancement to uterine myometrium were seen. On T1WI, the signal intensity of fluid was seen to be high in eight cases, low or intermediate in two, and of differing intensity in one. Ten cases showed high signal intensity on T2WI, whereas in one case in which high signal intensity was seen on T1WI, there was low signal intensity(shading). In three cases the contralateral ovary contained an endometrioma. Other features included ascites in seven cases and peritoneal seeding in one. Malignant ovarian tumors arising from endometriosis showed radiologic features of malignancy:they were larger than 10cm, there was enhancement of the wall and septa, and a papillary nodule or solid portion was present. However, the presence of hyperintense fluid, as seen on T1WI

  15. Radiologic findings of malignant tumors arising from ovarian endometriosis

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eun Ju; Joo, Hee Jae [Ajou Univ. College of Medicine, Suwon (Korea, Republic of); Kim, Bo Hyun [SungkyunKwan Univ. College of Medicine, Seoul (Korea, Republic of)

    1999-11-01

    To determine the radiologic characteristics of malignant tumors arising from ovarian endometriosis. The radiologic findings of eleven patients with pelvic masses histologically confirmed as malignant ovarian tumors arising from endometriosis were retrospectively reviewed. All patients underwent MR, and six underwent ultrasonography. The findings were evaluated with regard to tumor size and shape, locularity, thickness and enhancement of the wall and septa, the presence of papillary nodule or solid portion, signal intensity of the locule, the presence of mass in contralateral ovary, ascites, local invasion, distant metastases, and the Pathologic diagnosis included clear cell carcinoma in six cases, endometrioid carcinoma in three, and mucinous cystadenocarcinoma of borderline malignancy and endometrial stromal sarcoma in one case each. Tumor size ranged from 8 to 20 (mean, 12.7)cm. The tumors were mixed in four cases, entirely cystic in three, predominantly cystic in three, and predominantly solid in one. Six cases were unilocular and five were multilocular. The wall and septa varied in thickness and regularity and were well enhanced in all but one case. In all cases papillary nodules or solid portions with similar enhancement to uterine myometrium were seen. On T1WI, the signal intensity of fluid was seen to be high in eight cases, low or intermediate in two, and of differing intensity in one. Ten cases showed high signal intensity on T2WI, whereas in one case in which high signal intensity was seen on T1WI, there was low signal intensity(shading). In three cases the contralateral ovary contained an endometrioma. Other features included ascites in seven cases and peritoneal seeding in one. Malignant ovarian tumors arising from endometriosis showed radiologic features of malignancy:they were larger than 10cm, there was enhancement of the wall and septa, and a papillary nodule or solid portion was present. However, the presence of hyperintense fluid, as seen on T1WI

  16. Expression of c-Kit and PDGFRα in epithelial ovarian tumors and tumor stroma

    OpenAIRE

    YI, CUNJIAN; LI, LI; CHEN, KEMING; LIN, SHENGRONG; LIU, XIANGQIONG

    2011-01-01

    The purpose of this study was to investigate the expression of c-Kit and platelet-derived growth factor receptor α (PDGFRα) in epithelial ovarian tumor cells and tumor stroma. The expression of c-Kit and PDGFRα in 71 malignant or benign epithelial ovarian tumor tissues and 20 normal ovarian tissues was evaluated by immunohistochemical staining. The expression of c-Kit and PDGFRα in 71 malignant epithelial ovarian tumors and tumor stroma tissue samples was analyzed. A significant increase (P

  17. [Expression and Clinical Significance of Numb and P53 Proteins in Epithelial Ovarian Carcinoma].

    Science.gov (United States)

    Xu, Min; He, Hong-Ju; Zhang, Huan; Wang, Ao; Chen, Jie

    2017-01-01

    To investigate the expression and clinical significance of Numb and P53 proteins in epithelial ovarian carcinoma. We co-tested the expressions of Numb and P53 proteins in epithelial ovarian tissues by immunohistochemistry, including 20 cases of normal tissues, 29 cases of benign tumors, 35 cases of borderline ovarian tumors and 87 cases of epithelial ovarian carcinoma. Their clinical significance was analyzed. The positive expression rates of Numb protein in normal ovarian tissues, benign ovarian tumors, borderline ovarian tumors and epithelial ovarian carcinoma were 5%, 13.8%, 51.4% and 70.1%, respectively, and with the rising trend and significantly difference among four groups ( P 0.05). The positive expression rates of P53 protein in normal ovarian tissues, benign ovarian tumors, borderline ovarian tumors and epithelial ovarian carcinoma were 0%, 3.4%, 28.6% and 63.2%, respectively, which had a gradually rising trend with significantly difference among four groups ( P ovarian tumors was significantly higher than those in normal ovarian tissues and benign ovarian tumors ( P ovarian carcinoma group was significantly higher than those in the rest three groups ( P 0.05). The expression of Numb protein was positive correlated with the expression of P53 protein in borderline ovarian tumors and epithelial ovarian carcinoma ( r =0.488, P ovarian carcinoma and two proteins might work together in the development process of epithelial ovarian carcinoma.

  18. Serum arylesterase and paraoxonase activities in patients with ovarian tumors

    Directory of Open Access Journals (Sweden)

    Slawomir Michalak

    2014-12-01

    Conclusion: ARE activity is higher in patients with ovarian cancer than in patients with benign ovarian tumors; however, the serum activity of ARE is similar between patients with cancer and healthy individuals.

  19. Tumor Filóides Borderline: Relato de caso

    Directory of Open Access Journals (Sweden)

    MARINA PIRASSOL TEPEDINO

    2016-12-01

    Full Text Available O presente artigo tem o objetivo de narrar o caso de uma jovem de 24 anos, que teve quadro de Tumor Filóides do tipo borderline, evidenciado durante cirurgia de excisão de fibroadenoma, e diagnosticado por exame histopatológico da lesão, sendo futuramente reabordado com nova cirurgia. O Tumor Filóides é uma neoplasia fibroepitelial incomum da mama, representando de 0,3 a 0,9% de todos os tumores primários daquele órgão. É comumente vista entre pacientes com 40-50 anos. Sendo mais raro ainda sua apresentação em jovens. Por fim este artigo apresenta breve revisão de literatura, mostrando que a conduta utilizada no caso foi correta.

  20. MRI for discriminating metastatic ovarian tumors from primary epithelial ovarian cancers.

    Science.gov (United States)

    Xu, Yanhong; Yang, Jia; Zhang, Zaixian; Zhang, Guixiang

    2015-08-28

    To find specific magnetic resonance imaging (MRI) features to differentiate metastatic ovarian tumors from primary epithelial ovarian cancers. Eleven cases with metastatic ovarian tumors and 26 cases with primary malignant epithelial ovarian cancers were retrospectively studied. All features such as patient characteristics, MRI findings and biomarkers were evaluated. The differences including laterality, configuration, uniformity of locules, diffusion weighted imaging (DWI) signal of solid components and enhancement of solid portions between metastatic ovarian tumors and primary epithelial ovarian cancers were compared by Fisher's exact test. Median age of patients, the maximum diameter of lesions and biomarkers were compared by the Mann-Whitney test. Patients with metastatic ovarian tumors were younger than patients with primary epithelial ovarian cancers in the median age (P = 0.015). Patients with bilateral tumors in metastatic ovarian tumors were more than those of primary epithelial ovarian cancers (P = 0.032). The maximum diameter of lesions in metastatic ovarian tumors was smaller than that of primary epithelial ovarian cancers (P = 0.005). The locules in metastatic ovarian tumors were more uniform than those of primary epithelial ovarian cancers (P = 0.024). The enhancement of solid portions in metastatic ovarian tumors showed more moderate than that of primary epithelial ovarian cancers (P = 0.037). There was no statistically significant difference between the two groups in configuration, DWI signal of solid components and ascites. Biomarkers such as CA125 and human epididymis protein 4 (HE4) in metastatic ovarian tumors showed less elevated than that of primary epithelial ovarian cancers. Significant differences between metastatic ovarian tumors and primary epithelial ovarian cancers were found in the median age of patients, laterality, the maximum diameter of lesions, uniformity of locules, enhancement patterns of solid portions and

  1. Metastatic Ovarian Tumor Masquerading as Atypical Pneumonia.

    Science.gov (United States)

    Robles Cartagena, Ivonne; Robles Cartagena, América; Delgado Flores, Glorilee; Monroig Quiles, Pedro; Cabanillas, Fernando; Báez, Luis; Luis Acabá; Santos Reyes, Luis; Vicens, Rafael

    2015-01-01

    Krukenberg tumor is a malignancy in the ovary from a primary lesion in the gastrointestinal tract and a metastatic signet ring cell adenocarcinoma to the ovary. Stomach is the most common primary site, but other organs can serve as a primary site. The lymphatic system is the most likely route for metastasis. CA 125 levels can be used for screening for early detection of ovarian metastasis as well as for monitoring the course of disease. The prognosis of Krukenberg tumor is poor and no curative treatment is currently available.

  2. MR findings of ovarian tumors with hormonal activity, with emphasis on tumors other than sex cord-stromal tumors

    International Nuclear Information System (INIS)

    Tanaka, Yumiko Oishi; Saida, Tsukasa Sasaki; Minami, Rie; Yagi, Takako; Tsunoda, Hajime; Yoshikawa, Hiroyuki; Minami, Manabu

    2007-01-01

    Sex cord-stromal tumors including granulosa cell tumor, thecoma, Sertoli stromal cell tumor and steroid cell tumor are noted for their hormonal activity. However, there are many kinds of ovarian tumors other than sex cord-stromal tumors and tumor-like conditions with endocrine manifestations. Cross-sectional imaging, especially MR, can provide precise features of ovarian tumors and uterine morphological change even in a clinically latent excess of estrogen. In this article, we demonstrate typical imaging findings of ovarian tumors with hormonal activity. We also shortly explain the mechanism of the virilization and hyperestrogenism caused by ovarian tumors and tumor-like conditions

  3. A nationwide study of serous “borderline” ovarian tumors in Denmark 1978–2002

    DEFF Research Database (Denmark)

    Hannibal, Charlotte Gerd; Vang, Russell; Junge, Jette

    2014-01-01

    OBJECTIVE: To describe the study population and estimate overall survival of women with a serous "borderline" ovarian tumor (SBT) in Denmark over 25 years relative to the general population. METHODS: The Danish Pathology Data Bank and the Danish Cancer Registry were used to identify 1487 women...... diagnosed with SBTs from 1978 to 2002. The histologic slides were collected from Danish pathology departments and reviewed by expert pathologists and classified as SBT/atypical proliferative serous tumor (APST) or noninvasive low-grade serous carcinoma (LGSC). Associated implants were classified...

  4. Twenty-five-year-old Woman with Bilateral Borderline Ovarian Tumour Desiring to Preserve Fertility - Case Report and Literature Review on the Current State of Fertility Preservation in Women with Borderline Ovarian Tumours.

    Science.gov (United States)

    Findeklee, S; Lotz, L; Heusinger, K; Hoffmann, I; Dittrich, R; Beckmann, M W

    2016-11-01

    Borderline ovarian tumours are semimalignant tumours occurring unilaterally or bilaterally with a peak incidence among women of reproductive age. Since the affected women often wish to preserve fertility, particular precautions must be taken when counselling the patient and obtaining consent prior to planning an individual treatment. Options for preserving fertility include an organ-sparing surgical procedure and cryopreservation of oocytes and/or ovarian tissue. In this article, we report on a 25-year-old patient with a bilateral seromucinous borderline tumour who desired all fertility-preserving options. In order to perform the procedure without delay, we opted to perform luteal phase stimulation prior to oocyte retrieval. We conclude by discussing the current literature on the state of fertility preservation in the treatment of borderline ovarian tumours.

  5. Recent alcohol consumption and risk of incident ovarian carcinoma

    DEFF Research Database (Denmark)

    Kelemen, Linda E; Bandera, Elisa V; Terry, Kathryn L

    2013-01-01

    Studies evaluating the association between alcohol intake and ovarian carcinoma (OC) are inconsistent. Because OC and ovarian borderline tumor histologic types differ genetically, molecularly and clinically, large numbers are needed to estimate risk associations.......Studies evaluating the association between alcohol intake and ovarian carcinoma (OC) are inconsistent. Because OC and ovarian borderline tumor histologic types differ genetically, molecularly and clinically, large numbers are needed to estimate risk associations....

  6. Efficacy of the echo pattern classification of ovarian tumors 2000 in conjunction with transvaginal ultrasonography for diagnosis of ovarian masses.

    Science.gov (United States)

    Tajima, Atsushi; Suzuki, Chikako; Kikuchi, Iwaho; Kasahara, Hanako; Koizumi, Akari; Nojima, Michio; Yoshida, Koyo

    2016-04-01

    Because of the need for rapid, accurate clinical differentiation between malignant and benign ovarian masses, we investigated the diagnostic efficacy of the echo pattern classification used together with transvaginal ultrasound. We classified, on the basis of six echo pattern types, transvaginal ultrasound images of 405 ovarian masses treated surgically between January 2011 and December 2012. We compared the resulting classifications to the postoperative histopathologic diagnoses and computed the diagnostic sensitivity and specificity of the echo pattern-based classification for malignancy. Our review yielded the following echo patterns: type I, n = 61; type II; n = 154; type III, n = 82; type IV, n = 61; type V, n = 34; and type VI, n = 13. Histopathologically, there were 75 borderline malignant/malignant tumors and 330 benign tumors. Diagnostic sensitivity was 80.0 % and specificity was 85.5 % when echo types I-III were categorized as benign and types IV-VI were categorized as malignant. Further, with respect to benign tumors: sensitivity and specificity for chocolate cysts were 85.5 and 88.4 %, respectively, and for dermoid cysts were 67.2 and 97.9 %, respectively. With the echo pattern classification, ovarian masses can be diagnosed easily and accurately upon transvaginal ultrasound.

  7. Accuracy of intra-operative frozen section and its role in the diagnostic evaluation of ovarian tumors.

    Science.gov (United States)

    Abudukadeer, A; Azam, S; Zunong, B; Mutailipu, A Zuoremu; Huijun, B; Qun, L

    2016-01-01

    Summary This retrospective study was undertaken to evaluate the accuracy and role of intra-operative frozen section in the diagnosis of ovarian tumors. Retrospective study of 804 ovarian frozen section results between June 2010 and June 2014 was examined to determine the accuracy of frozen section diagnosis. The intra-operative frozen section diagnosis was compared with the permanent (paraffin) section and the overall accuracy, sensitivity, specificity, and positive and negative predictive values of the frozen section were studied. The overall accuracy to determine the status of malignancy was 92.6%. There were 38 (7.4%) false negative and no false positive frozen section diagnoses.The sensitivity, specificity, and positive predictive and negative predictive values for benign ovarian tumors were 100.0%, 97.0%, 91.3%, and 100.0%, respectively; for borderline tumors they were 64.3%, 97.0%, 91.5%, and 94.0%, respectively, and for malignant tumors they were 90.0%, 100.0%, 100.0%, and 85.5%, respectively. This study concluded that frozen section appears to be an adequate technique for the histopathological diagnosis of ovarian tumors, with some limitations observed among borderline and mucinous tumors.

  8. Krukenberg Tumor: A Rare Cause of Ovarian Torsion

    Directory of Open Access Journals (Sweden)

    Sameer Sandhu

    2012-01-01

    Full Text Available Ovarian torsion is the fifth most common gynecological surgical emergency. Ovarian torsion is usually associated with a cyst or a tumor, which is typically benign. The most common is mature cystic teratoma. We report the case of a 43-year-old woman who came to the Emergency Department with rare acute presentation of bilateral Krukenberg tumors, due to unilateral ovarian torsion. In this case report, we highlight the specific computed tomography (CT features of ovarian torsion and demonstrate the unique radiological findings on CT imaging. Metastasis to the ovary is not rare and 5 to 10% of all ovarian malignancies are metastatic. The stomach is the common primary site in most Krukenberg tumors (70%; an acute presentation of metastatic Krukenberg tumors with ovarian torsion is rare and not previously reported in radiology literature.

  9. Uncommon vascular tumor of the ovary. Primary ovarian epithelioid hemangioendothelioma or vascular sarcomatous transformation in ovarian germ cell tumor?

    Science.gov (United States)

    Illueca, Carmen; Machado, Isidro; García, Ana; Covisa, Amparo; Morales, Javier; Cruz, Julia; Traves, Victor; Almenar, Sergio

    2011-12-01

    Epithelioid hemangioendothelioma (EHE) is an unusual vascular tumor, which usually occurs in the soft tissue, liver, breast, lung and bone. We submit a case of EHE, a tumor never before reported in the ovary. A 20-year-old woman was admitted with a medical history of unilateral ovarian tumor. The right ovary was totally removed and histologically, the tumor was composed of epithelioid cells with eosinophilic cytoplasm and prominent intracytoplasmic vacuoles associated with myxohyaline matrix. No morphologic evidence of germ cell tumor was observed. Immunohistochemically, the tumor cells were positive for CD31 and CD34. However, all germ cell tumor markers were negative. The final diagnosis was EHE of the ovarian gland and sarcomatous transformation in ovarian germ cell tumor was excluded after extensive histopathological and immunohistochemical study. EHE is an uncommon vascular tumor, which is rarely seen in female genital tract and this is the first report of EHE in ovarian gland. Final diagnosis depends on histopathological and immunohistochemical features.

  10. [Fertility preservation, contraception and menopause hormone therapy in women treated for rare ovarian tumors: Guidelines from the French national network dedicated to rare gynaecological cancer].

    Science.gov (United States)

    Rousset-Jablonski, Christine; Selle, Fréderic; Adda-Herzog, Elodie; Planchamp, François; Selleret, Lise; Pomel, Christophe; Chabbert-Buffet, Nathalie; Daraï, Emile; Pautier, Patricia; Trémollières, Florence; Guyon, Frederic; Rouzier, Roman; Laurence, Valérie; Chopin, Nicolas; Faure-Conter, Cécile; Bentivegna, Enrica; Vacher-Lavenu, Marie-Cécile; Lhomme, Catherine; Floquet, Anne; Treilleux, Isabelle; Lecuru, Fabrice; Gouy, Sébastien; Kalbacher, Elsa; Genestie, Catherine; de la Motte Rouge, Thibault; Ferron, Gwenael; Devouassoux-Shisheboran, Mojgan; Kurtz, Jean-Emmanuel; Namer, Moise; Joly, Florence; Pujade-Lauraine, Eric; Grynberg, Michael; Querleu, Denis; Morice, Philippe; Gompel, Anne; Ray-Coquard, Isabelle

    2018-03-01

    Rare ovarian tumors include complex borderline ovarian tumors, sex-cord tumors, germ cell tumors, and rare epithelial tumors. Indications and modalities of fertility preservation, infertility management and contraindications for hormonal contraception or menopause hormone therapy are frequent issues in clinical practice. A panel of experts from the French national network dedicated to rare gynaecological cancers, and of experts in reproductive medicine and gynaecology have worked on guidelines about fertility preservation, contraception and menopause hormone therapy in women treated for ovarian rare tumors. A panel of 39 experts from different specialties contributed to the preparation of the guidelines, following the DELPHI method (formal consensus method). Statements were drafted after a systematic literature review, and then rated through two successive rounds. Thirty-five recommendations were selected, and concerned indications for fertility preservation, contraindications for ovarian stimulation (in the context of fertility preservation or for infertility management), contraceptive options (especially hormonal ones), and menopause hormone therapy for each tumor type. Overall, prudence has been recommended in the case of potentially hormone-sensitive tumors such as sex cord tumors, serous and endometrioid low-grade adenocarcinomas, as well as for high-risk serous borderline ovarian tumors. In the context of a scarce literature, a formal consensus method allowed the elaboration of guidelines, which will help clinicians in the management of these patients. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  11. Use of risk of malignancy index to indicate frozen section analysis in the surgical care of women with ovarian tumors.

    Science.gov (United States)

    van den Akker, Petronella A J; Zusterzeel, Petra L M; Aalders, Anette L; Snijders, Marc P L M; Samlal, Rahul A K; Vollebergh, Jos H A; Kluivers, Kirsten B; Massuger, Leon F A G

    2016-06-01

    To evaluate the importance of the risk of malignancy index (RMI) in the decision to perform frozen section analysis among women with ovarian tumors. A retrospective study was conducted in 11 centers in the Netherlands. Women who underwent surgical treatment of an ovarian mass with unknown histology between January 2005 and September 2009 were included. The RMI was calculated retrospectively. Frozen section analysis and RMI values were assessed for patients with benign, borderline, and malignant ovarian tumors on final histopathology. Overall, 670 women were included. Frozen sections were performed in 323 (48.2%) patients, of whom 206 (63.8%) were diagnosed with benign ovarian tumors, 55 (17.0%) with borderline tumors, and 62 (19.2%) with malignant tumors. Overall, 109 (16.3%) women had an RMI below 20, 106 (97.2%) of whom had benign histology results. Among 235 patients with an RMI over 100, 3 (1.3%) postmenopausal women had malignancies that were missed because frozen sections were not performed. Women with an RMI below 20 have a low risk of malignancy and therefore do not require frozen section analysis. Postmenopausal women with an RMI greater than 100 should be referred to centers where frozen sections can be performed, and proper facilities and expertise are available to perform staging procedures if necessary. Copyright © 2016 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

  12. FBXW7 is involved in the acquisition of the malignant phenotype in epithelial ovarian tumors.

    Science.gov (United States)

    Kitade, Shoko; Onoyama, Ichiro; Kobayashi, Hiroaki; Yagi, Hiroshi; Yoshida, Sachiko; Kato, Masaya; Tsunematsu, Ryosuke; Asanoma, Kazuo; Sonoda, Kenzo; Wake, Norio; Hata, Kenichiro; Nakayama, Keiichi I; Kato, Kiyoko

    2016-10-01

    FBXW7 is a ubiquitin ligase that mediates ubiquitylation of oncoproteins, such as c-Myc, cyclin E, Notch and c-Jun. FBXW7 is a known tumor-suppressor gene, and mutations in FBXW7 have been reported in various human malignancies. In this study, we examined the sequences of the FBXW7 and p53 genes in 57 ovarian cancer clinical samples. Interestingly, we found no FBXW7 mutations associated with amino acid changes. We also investigated FBXW7 expression levels in 126 epithelial ovarian tumors. FBXW7 expression was negatively correlated with the malignant potential of ovarian tumors. That is to say, FBXW7 expression levels in ovarian cancer samples were significantly lower than those in borderline and benign tumors (P carcinoma samples were the lowest among four major histological subtypes. In addition, p53-mutated ovarian cancer samples showed significantly lower levels of FBXW7 expression compared with p53 wild-type cancer samples (P PCR sequencing experiments revealed that 5'-upstream regions of FBXW7 gene in p53-mutated samples were significantly higher methylated compared with those in p53 wild-type samples (P p53 mutations might suppress FBXW7 expression through DNA hypermethylation of FBXW7 5'-upstream regions. Thus, FBXW7 expression was downregulated in ovarian cancers, and was associated with p53 mutations and the DNA methylation status of the 5'-upstream regions of FBXW7. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  13. Preoperative risk stratification of children with ovarian tumors.

    Science.gov (United States)

    Madenci, Arin L; Levine, Bat-Sheva; Laufer, Marc R; Boyd, Theonia K; Voss, Stephen D; Zurakowski, David; Frazier, A Lindsay; Weldon, Christopher B

    2016-09-01

    The appropriate operative approach to pediatric patients with ovarian tumors must balance real risk of malignancy with maximal preservation of reproductive potential. We evaluate preoperative risk of malignancy in order to more precisely guide treatment, so as to err on the side of ovarian preservation if at all possible. We retrospectively reviewed the records of all patients undergoing surgical intervention for ovarian tumors at a single institution. The primary endpoint was ovarian malignancy. Of 502 patients who underwent surgery for ovarian tumors, 44 (8.8%) had malignancies. Malignancy rate (95% confidence interval) was low for cystic lesions tumor marker-negative heterogeneous lesions tumor marker-positive heterogeneous lesions (66.7%, 35.4-87.9%) and solid tumors ≥9cm (69.2%, 16.2-40.3%). Intermediate risk tumors included cystic tumors ≥9cm (6.8%, 3.5-20.7%), tumor marker-negative heterogeneous lesions ≥9cm (31.2%, 18.0-48.6%), and solid tumors ovarian-sparing approach, which warrants prospective application and validation. Ultimately, the decision to pursue an oncologic surgery with oophorectomy and staging (as opposed to fertility-preserving surgery) should be made after individualized discussion involving the surgeon, patient, and family. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Metastatic Bilateral Malignant Ovarian Tumors Associated with Pregnancy

    Directory of Open Access Journals (Sweden)

    Savita Rani Singhal

    2009-06-01

    Conclusion: Because platinum-based chemotherapy can be safely given during pregnancy, hysterectomy can be avoided in cases of bilateral malignant ovarian tumors if the uterus is not grossly involved, so allowing preservation of an existing pregnancy.

  15. Steroid hormone synthesis by the ovarian stroma surrounding epithelial ovarian tumors: a potential mechanism in ovarian tumorigenesis.

    Science.gov (United States)

    Blanco, Luis Z; Kuhn, Elisabetta; Morrison, Jane C; Bahadirli-Talbott, Asli; Smith-Sehdev, Anne; Kurman, Robert J

    2017-04-01

    Epithelial ovarian tumors are responsive to steroid hormone stimulation and the ovarian stroma may have a direct role in this process. We evaluated immunohistochemical markers of sex-steroid differentiation and steroidogenesis (calretinin, inhibin, steroidogenic factor 1), steroid enzymes involved in hormone biosynthesis (CYP17, CYP19, HSD17β1, AKR1C3), and hormone receptors (estrogen receptor, progesterone receptor, and androgen receptor) in 101 epithelial ovarian tumors and in normal structures implicated in ovarian carcinogenesis (ovarian surface epithelium and cortical inclusion cysts) in an attempt to elucidate this process. We hypothesized that ovarian stroma immediately adjacent to tumors express markers of sex-steroid differentiation and steroidogenesis and steroid enzymes whereas the epithelium contains corresponding hormone receptors. As the findings in seromucinous, endometrioid, and clear cell neoplasms, tumors closely associated with endometriosis, were very similar, these were combined into a group designated 'endometriosis-related tumors.' Significantly increased expression of markers of sex-steroid differentiation and steroidogenesis was found in stroma immediately adjacent to endometriosis-related tumors (P=0.003) and mucinous tumors (primary and metastatic mucinous tumors were combined because of similar findings) (Povarian stroma. In addition, sex-steroid enzymes were increased in stroma adjacent to endometriosis-related tumors (P=0.02) and mucinous tumors (P=0.02) compared with more distant stroma. Steroid hormone receptors showed greater expression in epithelium compared with stroma in the endometriosis-related tumors (P=0.0009), low-grade serous tumors (Ptumors, which may be due to the fact that they are not derived from müllerian epithelium. In conclusion, our findings strongly support the view that the stroma surrounding epithelial tumors in the ovary is activated to elaborate steroid hormones which may stimulate further neoplastic growth

  16. Risk for borderline ovarian tumours after exposure to fertility drugs: results of a population-based cohort study.

    Science.gov (United States)

    Bjørnholt, Sarah Marie; Kjaer, Susanne Krüger; Nielsen, Thor Schütt Svane; Jensen, Allan

    2015-01-01

    Do fertility drugs increase the risk for borderline ovarian tumours, overall and according to histological subtype? The use of any fertility drug did not increase the overall risk for borderline ovarian tumours, but an increased risk for serous borderline ovarian tumours was observed after the use of progesterone. Many epidemiological studies have addressed the connection between fertility drugs use and risk for ovarian cancer; most have found no strong association. Fewer studies have assessed the association between use of fertility drugs and risk for borderline ovarian tumours, and the results are inconsistent. A retrospective case-cohort study was designed with data from a cohort of 96 545 Danish women with fertility problems referred to all Danish fertility clinics in the period 1963-2006. All women were followed for first occurrence of a borderline ovarian tumour from the initial date of infertility evaluation until a date of migration, date of death or 31 December 2006, whichever occurred first. The median length of follow-up was 11.3 years. Included in the analyses were 142 women with borderline ovarian tumours (cases) and 1328 randomly selected sub-cohort members identified in the cohort during the follow-up through 2006. Cases were identified by linkage to the Danish Cancer Register and the Danish Register of Pathology by use of personal identification numbers. To obtain information on use of fertility drugs, hospital files and medical records of infertility-associated visits to all Danish fertility clinics were collected and supplemented with information from the Danish IVF register. We used case-cohort techniques to calculate rate ratios (RRs) and corresponding 95% confidence intervals (CIs) for borderline ovarian tumours, overall and according to histological subtype, associated with the use of any fertility drug or five specific groups of fertility drugs: clomiphene citrate, gonadotrophins (human menopausal gonadotrophins and follicle

  17. Expression and clinical implication of Beclin1, HMGB1, p62, survivin, BRCA1 and ERCC1 in epithelial ovarian tumor tissues.

    Science.gov (United States)

    Ju, L-L; Zhao, C Y; Ye, K-F; Yang, H; Zhang, J

    2016-05-01

    The aim of the present study is to investigate the differential expression of Beclin1, HMGB1, p62, survivin, ERCC1 and BRCA1 protein in epithelial ovarian cancer (EOC) and to evaluate the relationship between autophagy and platinum resistance of EOC patients during platinum-based chemotherapy with the protein expression. Expression of Beclin1, HMGB1, p62, survivin, ERCC1 and BRCA1 were detected with immunohistochemistry in 60 patients, including 39 with epithelial ovarian cancer (EOC), 13 benign epithelial ovarian tumor tissue (BET) and 8 borderline ovarian tumor tissue. Beclin, p62 and ERCC1 expression was significantly higher in the EOC than the BET (p0.05). BRCA1 expression was lower in EOC than BET (pepithelial ovarian cancer.

  18. The role of computed tomography in diagnosis of ovarian tumors

    International Nuclear Information System (INIS)

    Yasuda, Yukihiko; Kohchiyama, Masahiko; Tsuru, Hiroshi; Shirai, Shigeo; Kikuchi, Shigeru; Koganemaru, Michihiko; Ohtake, Hisashi

    1985-01-01

    CT is useful in the diagnosis of pelvic tumors. CT can differenciate solid from cystic, and benign from malignant tumors and further provide important diagnostic informations for differential diagnosis. Twenty cases of ovarian tumors have been studied at Kurume University Hospital. This included 3 cystadenomas, 7 cystadenocarcinomas, 5 cystic teratomas, 2 endometriosis cysts and 3 metastatic ovarian cancers. CT was very valuable in differenciation of benign from malignant lesions on the basis of contrast enhancement, presence of ascites and adheison as well as irregularity of the cyst walls. It was difficult to differenciate ovarian tumors on the basis of the density of the tumor or calcification in the wall of the tumor. Cystic teratomas were diagnosed quite accurately in all cases because of its specific CT findings. Differenciation of endometriosis cysts of the ovary was difficult from degenerated uterine myoma. (author)

  19. Novel population of small tumour-initiating stem cells in the ovaries of women with borderline ovarian cancer

    Science.gov (United States)

    Virant-Klun, Irma; Stimpfel, Martin

    2016-01-01

    Small stem cells with diameters of up to 5 μm previously isolated from adult human ovaries indicated pluripotency and germinal lineage, especially primordial germ cells, and developed into primitive oocyte-like cells in vitro. Here, we show that a comparable population of small stem cells can be found in the ovarian tissue of women with borderline ovarian cancer, which, in contrast to small stem cells in “healthy” ovaries, formed spontaneous tumour-like structures and expressed some markers related to pluripotency and germinal lineage. The gene expression profile of these small putative cancer stem cells differed from similar cells sorted from “healthy” ovaries by 132 upregulated and 97 downregulated genes, including some important forkhead box and homeobox genes related to transcription regulation, developmental processes, embryogenesis, and ovarian cancer. These putative cancer stem cells are suggested to be a novel population of ovarian tumour-initiating cells in humans. PMID:27703207

  20. Borderline gastric stromal tumor: diagnosis by ultrasound and computed tomography; Tumor estromal borderline del estomago diagnostico por imagen en ecografia y TC

    Energy Technology Data Exchange (ETDEWEB)

    Feijoo, R.; Rubio, P. J.; Lopez, J. I.; Borderias, A.; Placeres, A. [Hospita San Jorge. Huesca (Spain)

    2000-07-01

    Gastrointestinal stromal tumors (GIST) are a type of undifferentiated stromal tumor that is recently being diagnosed more frequently owing to the introduction of new immunohistochemical techniques. Their main feature, indispensable for the definitive diagnosis, is immunohistochemical evidence of the presence of CD34-positive cells. We present a case of GIST of borderline malignancy involving the outer wall of the stomach, describing the ultrasound and computed tomography images and their correlation with the pathological features. (Author) 8 refs.

  1. Translational research in ovarian carcinoma : cell biological aspects of drug resistance and tumor aggressiveness

    NARCIS (Netherlands)

    Zee, Ate Gerard Jan van der

    1994-01-01

    In this thesis diverse cell biological features that in cultured (ovarian) tumor cells have been linked to drug resistance and/or tumor aggressiveness are studied in tumor specimens of epithelial ovarian carcinomas.

  2. Alfa-fetoprotein secreting ovarian sex cord-stromal tumor

    Directory of Open Access Journals (Sweden)

    Kusum D Jashnani

    2013-01-01

    Full Text Available Ovarian sex cord-stromal tumors are relatively infrequent neoplasms that account for approximately 8% of all primary ovarian tumors. They are a heterogeneous group of neoplasms composed of cells derived from gonadal sex cords (granulosa and Sertoli cells, specialized gonadal stroma (theca and Leydig cells, and fibroblasts. They may show androgenic or estrogenic manifestations. We report such a tumor associated with markedly raised serum alpha-fetoprotein (AFP levels in a young female presenting with a mass and defeminising symptoms. Serum AFP levels returned to normal on removal of tumor.

  3. Update on rare epithelial ovarian cancers: based on the Rare Ovarian Tumors Young Investigator Conference.

    Science.gov (United States)

    Jang, Ji Yon Agnes; Yanaihara, Nozomu; Pujade-Lauraine, Eric; Mikami, Yoshiki; Oda, Katsutoshi; Bookman, Michael; Ledermann, Jonathan; Shimada, Muneaki; Kiyokawa, Takako; Kim, Byoung Gie; Matsumura, Noriomi; Kaku, Tsunehisa; Kuroda, Takafumi; Nagayoshi, Yoko; Kawabata, Ayako; Iida, Yasushi; Kim, Jae Weon; Quinn, Michael; Okamoto, Aikou

    2017-07-01

    There has been significant progress in the understanding of the pathology and molecular biology of rare ovarian cancers, which has helped both diagnosis and treatment. This paper provides an update on recent advances in the knowledge and treatment of rare ovarian cancers and identifies gaps that need to be addressed by further clinical research. The topics covered include: low-grade serous, mucinous, and clear cell carcinomas of the ovary. Given the molecular heterogeneity and the histopathological rarity of these ovarian cancers, the importance of designing adequately powered trials or finding statistically innovative ways to approach the treatment of these rare tumors has been emphasized. This paper is based on the Rare Ovarian Tumors Conference for Young Investigators which was presented in Tokyo 2015 prior to the 5th Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup (GCIG). Copyright © 2017. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.

  4. Modern views on aetiology and pathogenesis of tumor growths and benign ovarian tumors

    Directory of Open Access Journals (Sweden)

    Serebrennikova K.G.

    2010-09-01

    Full Text Available The article represents modern data of aetiology and pathogenesis of tumor growths and benign ovarian tumors as systemic diseases of organism. These diseases appear on the cellular level and involve the presence of polymorphous metabolic, endocrine and immune disorders. Exogenous and endogenous risk factors of ovarian carcinomas are considered

  5. Regulatory T lymphocytes and transforming growth factor beta in epithelial ovarian tumors-prognostic significance.

    Science.gov (United States)

    Winkler, Izabela; Wilczynska, Barbara; Bojarska-Junak, Agnieszka; Gogacz, Marek; Adamiak, Aneta; Postawski, Krzysztof; Darmochwal-Kolarz, Dorota; Rechberger, Tomasz; Tabarkiewicz, Jacek

    2015-06-17

    Regulatory T lymphocytes (Treg) are characterized by the presence of CD4+ surface antigen. Today the transcription factor FOXP3 is considered to be the most specific marker of Treg cells. The aim of the study was to estimate the percentage of Treg in peripheral blood and the tissue of the epithelial ovarian tumor and blood serum TGF-beta concentrations and relationships between them. Moreover, the aim of the study was to answer the question whether the percentage of Treg lymphocytes affects the time of survival in patients with ovarian cancer. The patients were divided into four groups, depending on the histopathological examination result: I--a group without any pathology within the ovaries (C; n = 20), II--a group with benign tumors (B; n = 25), III - with borderline tumors (BR; n = 11), IV--a group with cancer of the ovary (M; n = 24). The percentage of Treg lymphocytes in peripheral blood and the tissue was assessed using the flow cytometry method. TGF-beta cytokine concentration was estimated with the ELISA immunoenzymatic test. Statistical analysis of the results was conducted using the computer program Statistica 10.0PL (StatSoft, Inc). No significant differences were found in percentages of Treg lymphocytes in peripheral blood between individual groups of patients (p = 0.11). However, we observed marked differences in the tissue of malignant and non-malignant tumors between individual groups of patients (p = 0.003). The analysis with the post hoc test revealed significantly higher TGF-beta concentration in the group of women with malignant tumors. Moreover, no relationship was found between TGF-beta concentration and the percentage of Treg cells in peripheral blood and tumors of the ovary. No correlation was found between the percentage of Treg lymphocytes in peripheral blood (p = 0.4) and the tissue of ovarian tumors (p = 0.3) and the time of survival of patients with ovarian cancer. The recruitment of Treg lymphocytes

  6. Serum level of tumor marker CA-125 in ovarian pathology

    International Nuclear Information System (INIS)

    Bagni, B.; Feggi, L.M.; Prandini, N.; Pasini, S.; Mollica, G.

    1987-01-01

    The tumor marker CA-125 is an embrional glycoprotein detectable in tissues derived from celomatic epitelium. Serum Ca-125 was determined by RIA in 66 patients with various ovarian pathologies (16 malignant at stage III-IV and 50 benign). Six patients with ovarian carcinoma were monitored during the first week after surgery and chemiotherapy for a total of 150 days of treatment. It has been observed that CA-125 serum level is consistently above the normal range (>35 U/ml) in all malignant diseases. In benign pathology, levels above the normal were found to be represented almost exclusively by ovarian endometriosis. Furthermore, the results demonstrate that chemiotherapy alone is capable of lowering CA-125 serum levels. This tumor marker may be of great advantage in diagnosis and follow-up of ovarian malignancy

  7. Monoclonal antibody against human ovarian tumor-associated antigens

    International Nuclear Information System (INIS)

    Poels, L.G.; Peters, D.; van Megen, Y.

    1986-01-01

    Mouse monoclonal antibodies (OV-TL 3) were raised against human ovarian tumor-associated antigens for diagnostic purposes. A cloned hybridoma cell line was obtained by fusion of murine myeloma cells with spleen lymphocytes from BALB/c mice immunized with a tumor cell suspension prepared from an ovarian endometrioid carcinoma. The antibodies were initially screened for their ability to bind on frozen sections of human ovarian carcinoma tissue and a negative reaction on gastric carcinoma tissue by indirect immunofluorescence. The reactivity of the selected OV-TL 3 clone (IgG1 subclass) was studied on normal and neoplastic tissues as well as on a cell line derived from the original tumor cell suspension used for immunization. OV-TL 3 antibodies stained frozen sections of human ovarian carcinomas of the following histological types: serous, mucinous, endometrioid, and clear cell. No reaction was found with breast cancers or other nongynecological tumors. No differences in staining pattern were observed between primary and metastatic ovarian carcinomas. OV-TL 3 antibodies brightly stained ovarian carcinoma cell clusters in ascitic fluids and left unstained mesothelial cells and peripheral blood cells. The OV-TL 3-defined antigen also remained strongly expressed on a cell line derived from the endometrioid ovarian carcinoma originally used for generation of OV-TL 3 clone. Reactivity was weak and irregular in a few ovarian cysts, while traces of fluorescence were sometimes detected in epithelial cells lining the female genital tract. In only 3 specimens of 15 endometrium carcinomas was weak focal reactivity with OV-TL 3 antibodies observed. The results of the immunofluorescence study were confirmed by the more sensitive avidin-biotin method and by 125 I-labeled OV-TL 3 antibodies

  8. Staging procedures in patients with mucinous borderline tumors of the ovary do not reveal peritoneal or omental disease

    NARCIS (Netherlands)

    Decker, K. De; Speth, S.; Brugge, H.G. ter; Bart, J.; Massuger, L.F.A.G.; Kleppe, M.; Kooreman, L.F.; Kruitwagen, R.F.; Kruse, A.J.

    2017-01-01

    OBJECTIVES: Staging in case of a borderline tumor of the ovary (BOT) is a controversial issue. Upstaging is not uncommon, but this occurs especially with presumed stage I serous borderline tumors. There are only a few documented cases of BOTs of non-serous histology that were not confined to the

  9. p53 signature and serous tubal in-situ carcinoma in cases of primary tubal and peritoneal carcinomas and serous borderline tumors of the ovary.

    Science.gov (United States)

    Leonhardt, Karoline; Einenkel, Jens; Sohr, Sindy; Engeland, Kurt; Horn, Lars-Christian

    2011-09-01

    The objective of this study was to evaluate the role of the fimbriated end and nonfimbriated epithelium of fallopian tubes with regard to p53 signature, tubal intraepithelial lesions in transition (TILT), and serous tubal in-situ carcinoma (STIC) in cases of different kinds of serous pelvic cancer. This study immunohistochemically evaluated (by Ki-67 and p53 staining) the presence of p53 signature, TILT lesions, and STIC in 14 consecutive cases of prophylactic salpingo-oophorectomy in women with BRCA-1/2 mutation (bilateral salpingo-oophorectomy), 11 cases of macroscopically inconspicuous adnexae of patients with primary contralateral tubal cancer (TC), 9 cases of primary peritoneal cancer (PPC), and 10 cases of serous ovarian borderline tumors, evaluating the fallopian tubes (using the Sectioning and Extensively Examining the FIMbria protocol), ovarian surface epithelium, and ovarian cortical inclusion cysts. The frequencies of p53 signature, TILT, and STIC were 35.7%, 7.1%, and 0% in cases of prophylactic surgery, 18.2%, 9.1%, and 18.2% in TC, and 11.1%, 0%, and 33.3% in PPC. These precursor lesions were missed during the initial routine screening and were found in the fimbriated end of the fallopian tubes in 94%. In 1 case of PPC, staining for p53 was negative in STIC. The studied adnexal tissue of serous ovarian borderline tumor and ovarian cortical inclusion cysts of all cases showed no alterations according to p53 signature, TILT, or STIC. STIC and p53 signature as precursor lesions of pelvic serous cancer were seen in macroscopically inconspicuous contralateral fallopian tubes in unilateral TC, in patients with elective bilateral salpingo-oophorectomy, and in patients affected by PPC. Therefore, we propose the complete processing of adnexal tissue and the use of step sectioning to establish the correct diagnosis. Immunohistochemistry for p53 and ki-67 may aid in the diagnosis, but is not necessary for routine investigation.

  10. Effect of pantethine on ovarian tumor progression and choline metabolism

    Directory of Open Access Journals (Sweden)

    Marie-France Penet

    2016-11-01

    Full Text Available Epithelial ovarian cancer remains the leading cause of death from gynecologic malignancy among women in developed countries. New therapeutic strategies evaluated with relevant preclinical models are urgently needed to improve survival rates. Here we have assessed the effect of pantethine on tumor growth and metabolism using magnetic resonance imaging (MRI and high-resolution proton magnetic resonance spectroscopy (MRS in a model of ovarian cancer. To evaluate treatment strategies, it is important to use models that closely mimic tumor growth in humans. We therefore used an orthotopic model of ovarian cancer where a piece of tumor tissue, derived from an ovarian tumor xenograft, is engrafted directly onto the ovary of female mice, to maintain the tumor physiological environment. Treatment with pantethine, the precursor of vitamin B5 and active moiety of coenzyme A, was started when tumors were approximately 100 mm3, and consisted of a daily i.p. injection of 750 mg/kg in saline. Under these conditions, no side effects were observed. High-resolution 1H MRS was performed on treated and control tumor extracts. A dual-phase extraction method based on methanol/chloroform/water was used to obtain lipid and water-soluble fractions from the tumors. We also investigated effects on metastases and ascites formation. Pantethine treatment resulted in slower tumor progression, decreased levels of phosphocholine and phosphatidylcholine, and reduced metastases and ascites occurrence. In conclusion, pantethine represents a novel potential, well-tolerated, therapeutic tool in patients with ovarian cancer. Further in vivo preclinical studies are needed to confirm the beneficial role of pantethine and to better understand its mechanism of action.

  11. Molecular genetic analysis of tumor suppressor genes in ovarian cancer

    International Nuclear Information System (INIS)

    Lee, Je Ho; Park, Sang Yun

    1992-04-01

    To examine the loci of putative tumor suppressor genes in ovarian cancers, we performed the molecular genetic analysis with fresh human ovarian cancers and observed the following data. Frequent allelic losses were observed on chromosomes 4p(42%), 6p(50%), 7p(43%), 8q(31%), 12p(38%), 12q(33%), 16p(33%), 16q(37%), and 19p(34%) in addition to the previously reported 6q, 11p, and 17p in ovarian caroinomas. we have used an additional probe, TCP10 to narrow down the deleted region on chromosome 6q. TCP10 was reported to be mapped to 6q 25-27. Allelic loss was found to be 40% in epithelial ovarian caroinomas. This finding suggests that chromosome 6q 24-27 is one of putative region haboring the tumor suppressor gene of epithelial ovarian cancer (particularly serous type). To examine the association between FAL(Fractional Allelic Loss) and histopathological features, the FAL value on each phenotypically different tumor was calculated as the ratio of the number of allelic losses versus the number of cases informative in each chromosomal arm. The average FALs for each phenotypically different tumor were: serous cystoadenocarcinomas. FAL=0.31 : mucinous 0.12 : and clear cell carcinoma. FAL=0.20. (Author)

  12. Maternal and fetal Outcome of pregnancies complicated by ovarian tumor

    International Nuclear Information System (INIS)

    Ambreen, A.; Anwar, K.; Hussain, A.

    2010-01-01

    Introduction: Ovarian tumors when occur, endanger two lives, mother and that of fetus. It becomes a therapeutic challenge to evaluate the necessity of immediate intervention for maternal indication versus delaying therapy for fetal indication. Majority of these cysts are benign and usually are functional cysts, dermoid or cyst adenomas. 2-5% of adnexal masses during pregnancy are true malignant neoplasms. Ovarian cancer being the second most frequent gynaecological cancer complicating pregnancy has an average estimated incidence of 1 in 2500 deliveries. Keeping in view all that, a study was conducted in Fatima Memorial Hospital to see maternal and fetal outcome of pregnancies complicated by ovarian tumors. Objective: To determine the maternal and fetal outcome of pregnancies complicated by ovarian tumors. Study Design: Case series descriptive study. Setting: The study was conducted in obstetrics and gynaecology department of Fatima Memorial Hospital, Lahore. Duration of Study: This study was conducted for one year. Subjects and Method: All 14500 pregnant ladies, who visited antenatal clinic and emergency of Fatima Memorial Hospital Lahore for one year, were considered to sort out pregnancies complicated by a co-existent ovarian mass of > 5 cm. Results: Of all 36 patients, included in current study, 24 had surgical and 12 had conservative management. Obstetric out-come revealed one preterm delivery after conservative management. Surgical intervention resulted in two abortions, two pre-term and twenty term deliveries. In both groups, the ratio of abdominal and vaginal delivery was 1:2 respectively. Fetal outcome revealed only one preterm and one IUGR infant in conservative group while surgically managed group revealed two preterm infants, two IUGR and one infant with septicemia. Conclusion: Surgical intervention is a reasonable approach to deal with cases of ovarian tumors with pregnancy, but conservative management may also have comparable obstetric outcome provided

  13. Ovarian Tumor Cells Studied Aboard the International Space Station (ISS)

    Science.gov (United States)

    2001-01-01

    In August 2001, principal investigator Jeanne Becker sent human ovarian tumor cells to the International Space Station (ISS) aboard the STS-105 mission. The tumor cells were cultured in microgravity for a 14 day growth period and were analyzed for changes in the rate of cell growth and synthesis of associated proteins. In addition, they were evaluated for the expression of several proteins that are the products of oncogenes, which cause the transformation of normal cells into cancer cells. This photo, which was taken by astronaut Frank Culbertson who conducted the experiment for Dr. Becker, shows two cell culture bags containing LN1 ovarian carcinoma cell cultures.

  14. Ovarian steroid cell tumor in women with polycystic ovarian syndrome: a case report

    Directory of Open Access Journals (Sweden)

    Yarandi F

    2013-04-01

    Full Text Available Background: Steroid cell tumor is one of the rare ovarian tumors and forms 0.1% of all ovarian tumors, divided to three subgroups. Steroid cell tumor that are not otherwise specified (NOS are the most common type and represent 60% of steroid cell tumors. One of the most known signs of this tumor is hormonal function, especially androgenic effects of it. Primary treatment consists of eradication of tumor via surgery.Case presentation: The patient is a 29 years old female with history of poly cystic ovarian syndrome since 10 years ago, who attended to the clinic of General Women Hospital of Tehran in January 2011. In pelvic ultrasonography, there was a 6449mm mass in the right adnexa consisting of homogeneous component. She underwent laparotomy and unilateral salpingoophorectomy was done. Pathological report was steroid cell tumor of ovary.Conclusion: The aim of this study is reporting one of the rare tumors of ovary and assessment of the correct way of diagnosis and treatment of it.

  15. Intraoperative Cytology of Ovarian Neoplasms with an Attempt to Grade Epithelial Tumors.

    Science.gov (United States)

    Bohara, Sangita; Jain, Shyama; Khurana, Nita; Shangpliang, Darilin M; Agarwal, Swapnil; Gandhi, Gauri

    2018-01-01

    Intraoperative cytology (IOC) is a simple and quick technique with excellent preservation of cellular details. In the present study, we have evaluated the role of IOC by various methods of smear preparation and compared it with frozen section diagnosis. A scoring system was followed for epithelial tumors for characterization and grading on the basis of cellularity, pattern, nuclear, cytoplasmic features, and background details. The study was conducted during a time span of 2 years in total 48 cases of ovarian tumors. Fine-needle aspiration cytology, touch/imprint, scrape, and crush techniques were used. The smears so prepared were processed for toluidine blue and Giemsa and Papanicolaou staining. Cases were cytomorphologically categorized into four groups: Indeterminate; unequivocally benign; borderline tumor with equivocal morphology; and unequivocally malignant (graded into well, moderately, and poorly differentiated). In our study, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 88.88, 96, 96, 88.88, and 92.31%, respectively, were recorded. This was comparable to frozen section diagnosis with a sensitivity, specificity, PPV, NPV, and accuracy of 85.18, 96.15, 95.83, 86.21, and 90.56%, respectively. In epithelial tumors, cytological grading correlated with histopathological grading in 85.29% cases of epithelial tumors. IOC gives comparable results to frozen section and can be used for intraoperative assessment of ovarian tumors. Grading of epithelial tumors on IOC can be performed and may become an important step in intraoperative decision-making for better management and outcome of the patient.

  16. A rare cause of virilization; Ovarian steroid cell tumor, not otherwise specified (NOS)

    OpenAIRE

    Taşdemir, Nicel; Çelik, Cem; Abalı, Remzi; Aksu, Erson; Öznur, Meltem; Yılmaz, Murat

    2012-01-01

    Sex cord–stromal tumors account for 5% of ovarian tumors and 2% of malignant ovarian tumors. Steroid cell tumors (SCT), not otherwise specified (NOS), are rare sex cord–stromal tumors of the ovary and account for less than 0.1% of all ovarian tumors. We report a rare case of a post-menopausal woman presented with hirsutism, virilism and with findings of hyperestrogenism.

  17. Autoantibodies to Tumor-Associated Antigens in Epithelial Ovarian Carcinoma

    Directory of Open Access Journals (Sweden)

    Benjamin Piura

    2009-01-01

    Full Text Available This review will focus on recent knowledge related to circulating autoantibodies (AAbs to tumor-associated antigens (TAAs in epithelial ovarian carcinoma. So far, the following TAAs have been identified to elicit circulating AAbs in epithelial ovarian carcinoma: p53, homeobox proteins (HOXA7, HOXB7, heat shock proteins (HSP-27, HSP-90, cathepsin D, cancer-testis antigens (NY-ESO-1/LAGE-1, MUC1, GIPC-1, IL-8, Ep-CAM, and S100A7. Since AAbs to TAAs have been identified in the circulation of patients with early-stage cancer, it has been speculated that the assessment of a panel of AAbs specific for epithelial ovarian carcinoma TAAs might hold great potential as a novel tool for early diagnosis of epithelial ovarian carcinoma.

  18. Reliability of preoperative evaluation of postmenopausal ovarian tumors.

    Science.gov (United States)

    Niemi, Riikka Johanna; Saarelainen, Sami Kristian; Luukkaala, Tiina Hannele; Mäenpää, Johanna Unelma

    2017-03-14

    Preoperative evaluation of ovarian tumors is challenging. This study was undertaken to evaluate the performance of conventional two-dimensional (2D) ultrasound and CA125 in predicting malignant or benign nature of pelvic masses, and to investigate if three-dimensional power Doppler (3DPD) ultrasound provides any added value. Ninety-six postmenopausal and four perimenopausal women with supposed ovarian tumors were examined by standardized 2D and 3DPD ultrasounds preoperatively. The tumors were evaluated using the risk of malignancy index (RMI), International Ovarian Tumors Analysis (IOTA) group simple rules, expert opinion, IOTA logistic regression model 2 (LR2) and 3D vascular indices, and were postoperatively compared to histopathological results. Ninety-eight tumors turned out to be ovarian in origin. Of these, 66 were benign and 32 malignant. RMI (cut-off value 200), simple rules, expert opinion and LR2 (cut-off value 25) were used to predict malignant nature of the tumors and had sensitivities of 71.9, 90.6, 87.5 and 90.6%, and specificities of 80.3, 84.6, 92.4 and 77.3%, respectively. When the 3D vascularization flow index (VFI) was added to RMI and LR2, the accuracy of the test improved from 77.6 to 81.4% and from 81.6 to 86.5%, respectively, at the expense of sensitivity, while VFI gave no added benefit for simple rules and expert opinion. Agreement between two examiners using expert opinion was good (Cohen's kappa = 0.89). The subjective opinion of an expert seems to be the most reliable method in assessing ovarian tumors, and the 3DPD indices seem to provide no significant added value.

  19. Large malignant ovarian tumors during pregnancy: two cases

    Directory of Open Access Journals (Sweden)

    Xu D

    2014-11-01

    Full Text Available Dong Xu, Cheng Liang, Jing He Gynecological and Obstetrical Department, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China Abstract: The present study reports two cases of large ovarian malignancy during pregnancy, which is very rare. The two patients were received between Nov 2012 and Feb 2013 at Gynecological and Obstetrical Department, Women's Hospital, School of Medicine, Zhejiang University (People's Republic of China. Both cases present tumor sized more than 20 cm, with one case of 40 cm. Both patients underwent timely cesarean section, with survival of the Child, and successful removal of the tumor. All patients showed good outcome in the follow-up period. Therefore the large ovarian malignancy during pregnancy could be well treated after careful clinical evaluation. Keywords: ovarian malignancy, pregnancy, incidence

  20. Sarcoma-like mural nodule in a borderline mucinous tumor of the ovary: A rare entity

    Directory of Open Access Journals (Sweden)

    Prithwijit Ghosh

    2014-01-01

    Full Text Available Sarcoma-like mural nodule (SLMN is a very uncommon and misleading benign entity which may be associated with benign, borderline or malignant mucinous neoplasm of the ovary. It should be distinguished from other malignant mural nodules with sarcoma, carcinosarcoma or anaplastic carcinoma for proper management. We report a rare case of SLMN in a borderline mucinous tumor of the ovary in a 30-year-old lady. In spite of having confusing histopathological features the final diagnosis was made depending on the younger age of the patient, well circumscription of the nodule, absence of vascular invasion and immunohistochemical profile.

  1. Clinicopathological Spectrum of Ovarian Tumors: A 5‑Year ...

    African Journals Online (AJOL)

    1Department of Pathology, B. J. Medical College and Sassoon Hospital, Pune, Maharashtra, India. ABSTRACT. Background: Ovarian tumors are a ..... ovary and lines the epithelial inclusion cyst. But in recent years, a new hypothesis of tubal .... the manuscripts. Financial support and sponsorship. Nil. Conflicts of interest.

  2. Clinicopathological Spectrum of Ovarian Tumors: A 5‑Year ...

    African Journals Online (AJOL)

    Clinicopathological Spectrum of Ovarian Tumors: A 5‑Year Experience in a Tertiary Health Care Center. ... Materials and Methods: It was a retrospective observational study. The study was conducted in. Department of Pathology, B. J. Medical College Pune, India from July 2006 to June 2011. All the histopathology slides of ...

  3. MRI findings of uterine tumor resembling ovarian sex-cord tumor: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Sung Hwan; Kim, Hee Jin; Han, Hyun Young; Hwang, In Taek; Kim, Ju Heon; Lee, Seung Yeon [Eulji University Hospital, Eulji University School of Medicine, Daejeon (Korea, Republic of)

    2017-04-15

    Uterine tumor resembling ovarian sex-cord tumor is a very rare uterine neoplasm that was first described by Clement and Scully in 1976. Since then, approximately 70 cases have been reported. However, these case reports have mainly described and discussed the pathologic and clinical features, and few radiologic findings have been presented. We experienced a case of a uterine tumor resembling ovarian sex-cord tumor, which was considered a uterine leiomyoma or leiomyosarcoma upon initial impression at preoperative evaluation including transvaginal ultrasonography and pelvic magnetic resonance imaging. Its diagnosis was pathologically confirmed after total abdominal hysterectomy.

  4. Molecular Genetic Analysis of Ovarian Brenner Tumors and Associated Mucinous Epithelial Neoplasms: High Variant Concordance and Identification of Mutually Exclusive RAS Driver Mutations and MYC Amplification.

    Science.gov (United States)

    Tafe, Laura J; Muller, Kristen E; Ananda, Guruprasad; Mitchell, Talia; Spotlow, Vanessa; Patterson, Sara E; Tsongalis, Gregory J; Mockus, Susan M

    2016-03-01

    Benign ovarian Brenner tumors often are associated with mucinous cystic neoplasms, which are hypothesized to share a histogenic origin and progression, however, supporting molecular characterization is limited. Our goal was to identify molecular mechanisms linking these tumors. DNA from six Brenner tumors with paired mucinous tumors, two Brenner tumors not associated with a mucinous neoplasm, and two atypical proliferative (borderline) Brenner tumors was extracted from formalin-fixed, paraffin-embedded tumor samples and sequenced using a 358-gene next-generation sequencing assay. Variant calls were compared within tumor groups to assess somatic mutation profiles. There was high concordance of the variants between paired samples (40% to 75%; P tumor pairs showed KRAS hotspot driver mutations specifically in the mucinous tumor. In the two paired samples that lacked KRAS mutations, MYC amplification was detected in both of the mucinous and the Brenner components; MYC amplification also was detected in a third Brenner tumor. Five of the Brenner tumors had no reportable potential driver alterations. The two atypical proliferative (borderline) Brenner tumors both had RAS mutations. The high degree of coordinate variants between paired Brenner and mucinous tumors supports a shared origin or progression. Differences observed in affected genes and pathways, particularly involving RAS and MYC, may point to molecular drivers of a divergent phenotype and progression of these tumors. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  5. MAL2 and tumor protein D52 (TPD52 are frequently overexpressed in ovarian carcinoma, but differentially associated with histological subtype and patient outcome

    Directory of Open Access Journals (Sweden)

    Fanayan Susan

    2010-09-01

    Full Text Available Abstract Background The four-transmembrane MAL2 protein is frequently overexpressed in breast carcinoma, and MAL2 overexpression is associated with gain of the corresponding locus at chromosome 8q24.12. Independent expression microarray studies predict MAL2 overexpression in ovarian carcinoma, but these had remained unconfirmed. MAL2 binds tumor protein D52 (TPD52, which is frequently overexpressed in ovarian carcinoma, but the clinical significance of MAL2 and TPD52 overexpression was unknown. Methods Immunohistochemical analyses of MAL2 and TPD52 expression were performed using tissue microarray sections including benign, borderline and malignant epithelial ovarian tumours. Inmmunohistochemical staining intensity and distribution was assessed both visually and digitally. Results MAL2 and TPD52 were significantly overexpressed in high-grade serous carcinomas compared with serous borderline tumours. MAL2 expression was highest in serous carcinomas relative to other histological subtypes, whereas TPD52 expression was highest in clear cell carcinomas. MAL2 expression was not related to patient survival, however high-level TPD52 staining was significantly associated with improved overall survival in patients with stage III serous ovarian carcinoma (log-rank test, p Conclusions MAL2 is frequently overexpressed in ovarian carcinoma, and TPD52 overexpression is a favourable independent prognostic marker of potential value in the management of ovarian carcinoma patients.

  6. Diagnosis and Management of Ovarian Tumor in Mayer-Rokitansky-Küster-Hauser (MRKH Syndrome

    Directory of Open Access Journals (Sweden)

    Yali Miao

    2018-01-01

    Full Text Available In the most recent publications on Mayer-Rokitansky-Küster-Hauser (MRKH syndrome, the uterine remnants and ovaries in patients may develop uterine remnant leiomyoma, adenomyosis, or ovarian tumor, and this can lead to problems in differential diagnosis. Here we summarize the diagnosis methods and available interventions for ovarian tumor in MRKH syndrome, with emphasis on the relevant clinical findings and illustrative relevant case. According to the clinical findings and illustrative relevant case, with the help of imaging techniques, ovarian tumors can be detected in the pelvis in patients with MRKH syndrome and evaluated in terms of size. Laparoscopy could further differentiate ovarian tumors into different pathological types. In addition, laparoscopic surgery not only is helpful for the diagnosis of MRKH combined ovarian tumor, but also has a good treatment role for excising ovarian tumor at the same time. Moreover, laparoscopic removals of ovarian tumor can be considered as a safe and reliable treatment for conservative management.

  7. Cytostatic and apoptotic effects of paclitaxel in human ovarian tumors.

    Science.gov (United States)

    Millenbaugh, N J; Gan, Y; Au, J L

    1998-01-01

    The present study evaluated the cytostatic and apoptotic effects of a 24-hr paclitaxel treatment in ovarian tumors. Three-dimensional histocultures of surgical specimens from patients (n = 17) were used. The cytostatic effect was measured by inhibition of 96-hr cumulative DNA precursor incorporation and induction of apoptosis was determined by morphological changes. Paclitaxel produced partial inhibition of DNA precursor incorporation in about 40% of tumors (maximum inhibition of approximately 30%) and induced apoptosis in about 90% of tumors (maximum apoptotic index of approximately 15%). In responsive tumors, maximum cytostatic and apoptotic effects were achieved at < or = 1 microM with no further enhancement by increasing the drug concentration to 10 microM. In individual tumors, the apoptotic effect inversely correlated with cytostatic effect (r2 = 0.27, p = 0.031), and the maximal apoptotic index correlated with the LI for the untreated controls (r2 = 0.38, p < 0.01). More than 95% of apoptotic cells after paclitaxel treatment were labeled with DNA precursor. The incomplete cytostatic and apoptotic effects of paclitaxel and the link between DNA synthesis and apoptosis in ovarian tumors are similar to our previous findings in other human solid tumors. These findings suggest that (a) apoptosis is the major paclitaxel effect in advanced ovarian tumors, (b) tumor sensitivity to drug-induced cytostatic effect is opposite to sensitivity to apoptotic effect, (c) paclitaxel-induced apoptosis increases with increased cell proliferation and is completed after DNA synthesis, and (d) further increasing the dose to elevate plasma concentration beyond 1 microM may not improve treatment outcome.

  8. Biologic Effects of Dopamine on Tumor Vasculature in Ovarian Carcinoma

    Directory of Open Access Journals (Sweden)

    Myrthala Moreno-Smith

    2013-05-01

    Full Text Available Chronic sympathetic nervous system activation results in increased angiogenesis and tumor growth in orthotopic mouse models of ovarian carcinoma. However, the mechanistic effects of such activation on the tumor vasculature are not well understood. Dopamine (DA, an inhibitory catecholamine, regulates the functions of normal and abnormal blood vessels. Here, we examined whether DA, an inhibitory catecholamine, could block the effects of chronic stress on tumor vasculature and tumor growth. Exogenous administration of DA not only decreased tumor microvessel density but also increased pericyte coverage of tumor vessels following daily restraint stress in mice. Daily restraint stress resulted in significantly increased tumor growth in the SKOV3ip1 and HeyA8 ovarian cancer models. DA treatment blocked stress-mediated increases in tumor growth and increased pericyte coverage of tumor endothelial cells. Whereas the antiangiogenic effect of DA is mediated by dopamine receptor 2 (DR2, our data indicate that DA, through DR1, stimulates vessel stabilization by increasing pericyte recruitment to tumor endothelial cells. DA significantly stimulated migration of mouse 10T1/2 pericyte-like cells in vitro and increased cyclic adenosine mono-phosphate (cAMP levels in these cells. Moreover, DA or the DR1 agonist SKF 82958 increased platinum concentration in SKOV3ip1 tumor xenografts following cisplatin administration. In conclusion, DA stabilizes tumor blood vessels through activation of pericyte cAMP-protein kinase A signaling pathway by DR1. These findings could have implications for blocking the stimulatory effects of chronic stress on tumor growth.

  9. Conservative Treatment of Serous Borderline Paratesticular Tumor in a Pediatric Patient.

    Science.gov (United States)

    Caroassai Grisanti, Simone; Martini, Alberto; Bigazzi, Barbara; Raspollini, Maria Rosaria; Delle Rose, Augusto; Villari, Donata; Nicita, Giulio

    2016-03-01

    Serous borderline tumors are rare neoplasms. Herein we report our conservative approach, whose rationale is neoplasm low-malignant potential. Tumor was removed under general anesthesia, and frozen section ruled out a germinal malignancy or a stromal tumor such as rhabdomyosarcoma. Ultrasound evaluation was initially performed every 3 months during the first 2 years, every 6 months during the next 3 years, and annually thereafter. After 8 years, the patient has not experienced any relapse, either clinical or ultrasonographical. In our opinion, conservative approach, whose final decision relies on intraoperative frozen section, represents the best option and does not jeopardize long-term oncological outcome. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Borderline phyllodes tumor of breast in a premenarchal girl: A relatively common tumor at an uncommon age

    Directory of Open Access Journals (Sweden)

    Akhil Kapoor

    2016-06-01

    Full Text Available Phyllodes tumors are relatively rare breast lesions that usually occur in the age group of 35 ‒ 55 years. It is a very rare diagnosis in young girls, particularly at prepubertal age. Because of the uncommon nature of this tumor in children, it may be misdiagnosed leading to inappropriate management. We report a case of a 9–year-old girl who was diagnosed as a case of borderline phyllodes tumor left breast. Simple mastectomy without axillary staging was performed. She has recovered well and is on follow up.

  11. Ovarian Sex Cord-stromal Tumors With Melanin Pigment: Report of a Previously Undescribed Phenomenon.

    Science.gov (United States)

    Taylor, Jennifer; McCluggage, W Glenn

    2017-11-14

    We report 2 ovarian sex cord-stromal tumors, a luteinized adult granulosa cell tumor and a cellular fibroma, with melanin pigment. These occurred in 44 and 61-yr-old patients, respectively. As far as we are aware, melanin pigment has not been described previously in an ovarian sex cord-stromal tumor, although it has been reported in a testicular Sertoli cell tumor. We review ovarian neoplasms containing melanin pigment.

  12. Reprogramming of the Ovarian Tumor Stroma by Activation of a Biomechanical ECM Switch

    Science.gov (United States)

    2016-09-01

    AWARD NUMBER: W81XWH-14-1-0178 TITLE: Reprogramming of the Ovarian Tumor Stroma by Activation of a Biomechanical ECM Switch PRINCIPAL...SUBTITLE 5a. CONTRACT NUMBER Reprogramming of the Ovarian Tumor Stroma by Activation of a Biomechanical ECM Switch 5b. GRANT NUMBER W81XWH-14-1...particular we, have characterized stromal cell infiltration of ovarian tumors and have shown extensive infiltration of tumor associated blood vessels as well

  13. p53 mutations in ovarian tumors, detected by temperature-gradient gel electrophoresis, direct sequencing and immunohistochemistry.

    Science.gov (United States)

    Kappes, S; Milde-Langosch, K; Kressin, P; Passlack, B; Dockhorn-Dworniczak, B; Röhlke, P; Löning, T

    1995-02-20

    Samples from 94 ovarian tumors, comprising 24 cystadenomas/adenofibromas, among them 6 benign and 18 borderline tumors, one benign Brenner tumor, 39 carcinomas, 17 sex-cord stromal tumors, 5 germ-cell tumors and 8 metastatic or recurrent neoplasms were screened for p53 aberrations by polymerase chain reaction (PCR), temperature-gradient gel electrophoresis (TGGE), direct sequencing and immunohistochemistry. All sex-cord stromal and germ-cell tumors showed wild-type p53, except for a heterozygous silent germ-line mutation in one androblastoma. Somatic p53 mutations were detected in only one tumor of the cystadenoma/adenofibroma series (4.2%), in contrast to 38.5% of the carcinomas, among them 57.1% of serous papillary carcinomas, and 12.5 to 22.2% of endometrioid and mucinous carcinomas. By direct sequencing, the mutations of 13 cases were qualified as mis-sense mutations (n = 10), or 1 to 2-bp deletions (n = 3). Only 2 cases were immunohistochemically positive in the absence of detectable p53-gene abnormalities. The presence of p53 aberrations was significantly correlated with high grade, but not with stage of disease. For 21 bilateral tumors and/or tumors spread to the peritoneum, samples from both ovaries and/or ascites were analyzed. Among these, 16 cases were identical as to the p53 genotype, 5 cases showed discordant p53 states in ovary and/or in ascites DNA. We conclude that somatic p53 mutations are very frequent in serous papillary carcinomas, particularly in tumors of high grade, bilaterality, and peritoneal spread, less frequent in other carcinoma types and extremely rare in borderline and benign tumors of the ovary.

  14. MR imaging findings of extraovarian endocervical mucinous borderline tumors arising from pelvic endometriosis

    Energy Technology Data Exchange (ETDEWEB)

    Yeo, Dong Myung; Rha, Sung Eun; Byun, Jae Young; Lee, Ahwon; Kim, Mee Ran [Seoul St. Mary' s Hospital, The Catholic University of Korea, Seoul (Korea, Republic of)

    2013-12-15

    We report MR imaging findings of a rare case of endocervical mucinous borderline tumor (MBT) involving the cul-de-sac and left fallopian tube arising from extensive pelvic endometriosis with pathologic correlation in a 35-year-old woman presented with vague pelvic pain. Endocervical MBT is a type of endometriosis-associated carcinoma. Imaging findings of endocervical MBT are unilocular or oligolocular cystic lesions with enhancing mural nodules, which are different from those of the more common intestinal type MBT.

  15. MR imaging findings of extraovarian endocervical mucinous borderline tumors arising from pelvic endometriosis

    International Nuclear Information System (INIS)

    Yeo, Dong Myung; Rha, Sung Eun; Byun, Jae Young; Lee, Ahwon; Kim, Mee Ran

    2013-01-01

    We report MR imaging findings of a rare case of endocervical mucinous borderline tumor (MBT) involving the cul-de-sac and left fallopian tube arising from extensive pelvic endometriosis with pathologic correlation in a 35-year-old woman presented with vague pelvic pain. Endocervical MBT is a type of endometriosis-associated carcinoma. Imaging findings of endocervical MBT are unilocular or oligolocular cystic lesions with enhancing mural nodules, which are different from those of the more common intestinal type MBT.

  16. Stages of Ovarian Low Malignant Potential Tumors

    Science.gov (United States)

    ... tests or procedures are used for staging. Staging laparotomy (a surgical incision made in the wall of ... treatment. Two types of standard treatment are used: Surgery The type of surgery (removing the tumor in ...

  17. ELF5 in epithelial ovarian carcinoma tissues and biological behavior in ovarian carcinoma cells.

    Science.gov (United States)

    Yan, Hongchao; Qiu, Linglin; Xie, Xiaolei; Yang, He; Liu, Yongli; Lin, Xiaoman; Huang, Hongxiang

    2017-03-01

    The expression of E74-like factor 5 (ELF5) in epithelial ovarian carcinoma tissues and its effects on biological behavior in ovarian carcinoma cells were assessed in search for a new approach for gene treatment of epithelial ovarian carcinoma. RT-PCR technology was applied to detect the expression of ELF5 mRNA in epithelial ovarian carcinoma (n=49), borderline ovarian epithelial tumor (n=19), benign ovarian epithelial tumor (n=31) and normal ovarian tissues (n=40). Then, we transfected recombinant plasmid pcDNA3.1‑ELF5+EGFP into human ovarian carcinoma SKOV3 cells (recombinant plasmid group) in vitro and screened out stably transfected cells to conduct multiplication culture. Western blot analysis was performed to detect the expression of ELF5 protein in the different groups. Flow cytometry was employed to detect cell apoptosis and cycles. ELF5 mRNA in epithelial ovarian carcinoma and borderline ovarian epithelial tumor tissues were significantly lower (Povarian epithelial tumor and normal ovarian tissues. ELF5 protein expression in the cells of recombinant plasmid group was significantly higher compared with empty plasmid and blank control groups. The capacity of cell reproductive recombinant plasmid group at each time point decreased (Povarian carcinoma SKOV3 cells and promoted apoptosis of human ovarian carcinoma SKOV3 cells inhibiting their growth and invasive capacity; and thus providing a new approach to gene treatment of ovarian carcinoma.

  18. Degenerated uterine leiomyomas mimicking malignant bilateral ovarian surface epithelial tumors

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Yi Boem Ha; Lee, Hae Kyung; Lee, Min Hee; Choi, Seo Youn; Chung, Soo Ho [Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon (Korea, Republic of)

    2017-07-15

    Uterine leiomyomas are the most common benign uterine neoplasms. Undegenerated uterine leiomyomas are easily recognizable by the typical imaging findings on radiologic studies. However, degenerated fibroids can have unusual and variable appearances. The atypical appearances due to degenerative changes may cause confusion in diagnosis of leiomyomas. In this article, we report a case of a patient with extensive cystic and myxoid degeneration of uterine leiomyoma, mimicking malignant bilateral ovarian surface epithelial tumors.

  19. Morphological and Immunohistochemical Reevaluation of Tumors Initially Diagnosed as Ovarian Endometrioid Carcinoma With Emphasis on High-grade Tumors.

    Science.gov (United States)

    Lim, Diana; Murali, Rajmohan; Murray, Melissa P; Veras, Emanuela; Park, Kay J; Soslow, Robert A

    2016-03-01

    Ovarian endometrioid carcinomas (OEC) of low grade have characteristic morphologic features, but high-grade tumors can mimic high-grade serous and undifferentiated carcinomas. We reviewed tumors initially diagnosed as OEC to determine whether a combination of pathologic and immunohistochemical features can improve histologic subclassification. Tumors initially diagnosed as OEC were reviewed using World Health Organization criteria. We also noted the presence of associated confirmatory endometrioid features (CEFs): (i) squamous metaplasia; (ii) endometriosis; (iii) adenofibromatous background; and (iv) borderline endometrioid or mixed Mullerian component. A tissue microarray was constructed from 27 representative tumors with CEF and 14 without CEF, and sections were stained for WT-1, p16, and p53. Of 109 tumors initially diagnosed as OEC, 76 (70%) tumors were classified as OEC. The median patient age was 55 years, and 75% of patients were younger than 60 years. Ninety-two percent presented with disease confined to the pelvis, and 87% of tumors were unilateral. The median tumor size was 11.8 cm. Only 3% of tumors were high grade (grade 3of 3). Eighty percent of cases had at least 1 CEF, and 59% had at least 2 CEFs. Eleven percent overexpressed p16, 0% overexpressed p53, and 3% expressed WT-1. Only 10% of patients died of disease at last follow-up. Thirty-three (33) tumors, or 30% of tumors originally classified as endometrioid, were reclassified as serous carcinoma (OSC). The median patient age was 54.5 years, and 59% of patients were younger than 60 years of age. Only 27% had disease confined to the pelvis at presentation, 52% of tumors were unilateral, and the median tumor size was 8 cm. Associated squamous differentiation, endometrioid adenofibroma, and endometrioid or mixed Mullerian borderline tumor (CEFs) were not present in any case, but 6% of patients had endometriosis. Approximately one half of the reclassified OSC demonstrated SET-pattern morphology

  20. Preoperative serum tetranectin, CA125 and menopausal status used as single markers in screening and in a risk assessment index (RAI) in discriminating between benign and malignant ovarian tumors

    DEFF Research Database (Denmark)

    Begum, F D; Høgdall, E; Kjaer, S K

    2009-01-01

    risk for OC for quick referral to highly specialized centers in gynecologic oncology. These aims were addressed in the present study by evaluating serum tetranectin (TN) and serum CA125 on a large number of pre- and postmenopausal women with ovarian tumors and controls. METHODS: The potential ability...... of the markers to discriminate between the four groups (208 benign ovarian tumor, 153 borderline ovarian tumor (BOT), 445 OC and 1333 age matched controls) in OC screening was examined. We also constructed a risk assessment index (RAI) for discrimination between tumor groups based on these variables...... and menopausal status. RESULTS: Highly significant differences in both TN and CA125 levels were found between all the four groups as well as between the different FIGO stages of OC patients. A very high probability of having OC or a benign tumor, respectively, was predicted by the RAI. CONCLUSIONS: In the case-control...

  1. A new tumor marker: CA125 for ovarian carcinomas

    International Nuclear Information System (INIS)

    Sakahara, H.; Endo, K.; Nakajima, K.

    1985-01-01

    To evaluate CA125 as a tumor marker for ovarian carcinomas, CA125 concentrations were measured by the simultaneous immunoradiometric assay. The binding of I-125 labeled monoclonal antibody to the bead-bound antigen was greatly influenced by many factors, such as the incubation time, pH, IgG concentrations of samples, the sequence of addition of the tracer and samples and so on. By applying the forward two-step assay, diminished binding was observed than in the simultaneous assay, probably due to the relatively low affinity of the antibody. This simultaneous immunoradiometric assay resulted in the ''prozone'' or ''hook'' effect at high CA125 samples and proper dilution was necessary to determine the accurate CA125 values. All 72 normal control subjects had low concentrations of under 35 U/ml. Elevated serum CA125 was observed in 43% (9/21) cases with malignant ovarian tumors, depending on the stage and the histopathological findings. All 4 serous cystadenocarcinomas and 2 of 3 endometrioid carcinomas were positive and the measurement of serum CA125 was useful in the sequential monitoring of these cases. In contrast, 51 benign gynecological diseases, none had elevated serum CA125 except one with follicular cyst. Among 75 cases with non-gynecological benign and malignant diseases, only 1 of 12 gastric carcinomas and 2 of 13 pancreatic carcinomas had elevated CA125 levels. In summary, CA125 is a promising and relatively specific marker for ovarian carcinomas

  2. Mutational analysis of BRAF and KRAS in ovarian serous borderline (atypical proliferative) tumours and associated peritoneal implants

    DEFF Research Database (Denmark)

    Ardighieri, Laura; Zeppernick, Felix; Hannibal, Charlotte G

    2014-01-01

    There is debate as to whether peritoneal implants associated with serous borderline tumours/atypical proliferative serous tumours (SBT/APSTs) of the ovary are derived from the primary ovarian tumour or arise independently in the peritoneum. We analysed 57 SBT/APSTs from 45 patients with advanced......), 34 (53.9%) had KRAS mutations and 14 (22%) had BRAF mutations, of which identical KRAS mutations were found in 34 (91%) of 37 SBT/APST-implant pairs and identical BRAF mutations in 14 (100%) of 14 SBT/APST-implant pairs. Wild-type KRAS and BRAF (at the loci investigated) were found in 11 (100%) of 11...... SBT/APST-implant pairs. Overall concordance of KRAS and BRAF mutations was 95% in 59 of 62 SBT/APST-implant (non-invasive and invasive) pairs (p identical KRAS or BRAF...

  3. Genetics and genomics of ovarian sex cord-stromal tumors.

    Science.gov (United States)

    Fuller, P J; Leung, D; Chu, S

    2017-02-01

    Ovarian sex cord-stromal tumors (SCST) represent approximately 8% of malignant ovarian tumors. The most common are granulosa cell tumors (GCT) which account for approximately 90% of malignant SCST. Recent studies have unraveled the key genomic and genetic events contributing to their pathogenesis. SCST are found in the hereditary syndromes: Peutz-Jeghers syndrome, Ollier disease and Maffucci syndrome, and DICER1 syndrome. Genomic studies have largely been limited to GCT where a number of recurring chromosomal abnormalities (monsomy and trisomy) have been identified although their contribution to pathogenesis remains unclear. In addition to the recurrent DICER1 mutations reported in non-hereditary cases of Sertoli cell and Sertoli-Leydig cell tumors, recurrent somatic mutations in both the juvenile (j) and adult (a) forms of GCT have been reported. Approximately 30% of jGCT contain a somatic mutation, the gsp oncogene, while a further 60% have an activating mutation in the AKT gene. In the case of aGCT, a well characterized mutation in the FOXL2 transcription factor (FOXL2 C134W) is found in almost all cases, which arguably defines the disease, although the molecular events that determine the stage, behavior and prognosis of aGCT remain to be determined. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Mutational profiles of Brenner tumors show distinctive features uncoupling urothelial carcinomas and ovarian carcinoma with transitional cell histology.

    Science.gov (United States)

    Pfarr, Nicole; Darb-Esfahani, Silvia; Leichsenring, Jonas; Taube, Eliane; Boxberg, Melanie; Braicu, Ioana; Jesinghaus, Moritz; Penzel, Roland; Endris, Volker; Noske, Aurelia; Weichert, Wilko; Schirmacher, Peter; Denkert, Carsten; Stenzinger, Albrecht

    2017-10-01

    Brenner tumors (BT) are rare ovarian tumors encompassing benign, borderline, and malignant variants. While the histopathology of BTs and their clinical course is well described, little is known about the underlying genetic defects. We employed targeted next generation sequencing to analyze the mutational landscape in a cohort of 23 BT cases (17 benign, 2 borderline, and 4 malignant) and 3 ovarian carcinomas with transitional cell histology (TCC). Copy number variations (CNV) were validated by fluorescence in-situ hybridization (FISH) and quantitative PCR-based copy number assays. Additionally, we analyzed the TERT promotor region by conventional Sanger sequencing. We identified 25 different point mutations in 23 of the analyzed genes in BTs and 10 mutations in 8 genes in TCCs. About 57% percent of mutations occurred in genes involved in cell cycle control, DNA repair, and epigenetic regulation processes. All TCC cases harbored TP53 mutations whereas all BTs were negative and none of the mutations observed in BTs were present in TCCs. CNV analysis revealed recurrent MDM2 amplifications in 3 out of 4 of the malignant BT cases with one case harboring a concomitant amplification of CCND1. No mutations were observed in the TERT promoter region in BTs and TCCs, which is mutated in about 50%-75% of urothelial carcinoma and in 16% of ovarian clear-cell carcinomas. In conclusion, our study highlights distinct genetic features of BTs, and detection of the triplet phenotype MDM2 amplification/TP53 wt/TERT wt may aid diagnosis of malignant BT in difficult cases. Moreover, selected genetic lesions may be clinically exploitable in a metastatic setting. © 2017 Wiley Periodicals, Inc.

  5. Serum tumor marker CA 125 for monitoring ovarian cancer during follow-up

    DEFF Research Database (Denmark)

    Tuxen, Malgorzata K.; Sölétormos, G; Dombernowsky, P

    2002-01-01

    CA 125 is currently widely applied in the management of patients with ovarian cancer. However, a change in results of CA 125, which should be considered significant, has not been defined. The aim of this study was to investigate the ability of CA 125 to signal progressive ovarian cancer during fo...... utility of serological tumor markers in patients with ovarian cancer....

  6. Ovarian tumor-initiating cells display a flexible metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, Angela S. [Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, VA (United States); Roberts, Paul C. [Biomedical Science and Pathobiology, Virginia Tech, Blacksburg, VA (United States); Frisard, Madlyn I. [Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, VA (United States); Hulver, Matthew W., E-mail: hulvermw@vt.edu [Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, VA (United States); Schmelz, Eva M., E-mail: eschmelz@vt.edu [Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, VA (United States)

    2014-10-15

    An altered metabolism during ovarian cancer progression allows for increased macromolecular synthesis and unrestrained growth. However, the metabolic phenotype of cancer stem or tumor-initiating cells, small tumor cell populations that are able to recapitulate the original tumor, has not been well characterized. In the present study, we compared the metabolic phenotype of the stem cell enriched cell variant, MOSE-L{sub FFLv} (TIC), derived from mouse ovarian surface epithelial (MOSE) cells, to their parental (MOSE-L) and benign precursor (MOSE-E) cells. TICs exhibit a decrease in glucose and fatty acid oxidation with a concomitant increase in lactate secretion. In contrast to MOSE-L cells, TICs can increase their rate of glycolysis to overcome the inhibition of ATP synthase by oligomycin and can increase their oxygen consumption rate to maintain proton motive force when uncoupled, similar to the benign MOSE-E cells. TICs have an increased survival rate under limiting conditions as well as an increased survival rate when treated with AICAR, but exhibit a higher sensitivity to metformin than MOSE-E and MOSE-L cells. Together, our data show that TICs have a distinct metabolic profile that may render them flexible to adapt to the specific conditions of their microenvironment. By better understanding their metabolic phenotype and external environmental conditions that support their survival, treatment interventions can be designed to extend current therapy regimens to eradicate TICs. - Highlights: • Ovarian cancer TICs exhibit a decreased glucose and fatty acid oxidation. • TICs are more glycolytic and have highly active mitochondria. • TICs are more resistant to AICAR but not metformin. • A flexible metabolism allows TICs to adapt to their microenvironment. • This flexibility requires development of specific drugs targeting TIC-specific changes to prevent recurrent TIC outgrowth.

  7. Inhibitory role of prohibitin in human ovarian epithelial cancer

    Science.gov (United States)

    Jia, Lin; Ren, Jian-Min; Wang, Yi-Ying; Zheng, Yu; Zhang, Hui; Zhang, Qing; Kong, Bei-Hua; Zheng, Wen-Xin

    2014-01-01

    Objectives: To characterize the exact individual roles of gonadotropins on ovarian epithelial carcinogenesis, an earlier study showed that prohibitin was significantly up-regulated by luteinizing hormone (LH). To further clarify the role of prohibitin in ovarian carcinogenesis and its association with LH, herein we studied the expression of prohibitin in various ovarian tissues including different developmental stages of ovarian epithelial tumors. Methods: A total of 135 samples were studied by immunohistochemistry. These included benign ovarian cases with follicles, ovarian surface epithelia and ovarian epithelial inclusions (OEI) (n=30), serous cystadenoma (n=14), serous borderline tumor (n=12), serous carcinoma (n=20), mucinous cystadenoma (n=10), mucinous borderline tumor (n=10), mucinous carcinomas (n=10), endometrioid carcinomas (n=12), poorly/undifferentiated carcinomas (n=5), and fallopian tube (n=12). Results: Strong and diffuse staining of prohibitin was detected in luteinized ovarian stromal cells, follicular cells, fallopian tube, and OEI with serous differentiation. A significantly higher prohibitin expression in luteinized stromal cells than in non-luteinized stromal cells was observed (POEI. However, compared to the level of prohibitin expression in OEI, it showed a trend of gradual loss from benign ovarian tumors, to borderline tumors and to carcinomas (POEI. Conclusions: These data further suggest that prohibitin plays a tumor suppressing role, which is probably associated with LH mediated protection role against ovarian epithelial carcinoma. In addition to the tumor suppressive role of prohibitin, it also plays a role in cellular differentiation, which may be helpful to differentiate ovarian mucinous tumors from the tumors with serous differentiation in clinical settings. More importantly, our findings are supportive that the ovarian epithelial cancers, particularly the serous cancers including those precursors with serous differentiation are

  8. Incidence of serous tubal intraepithelial carcinoma (STIC) by algorithm classification in serous ovarian tumor associated with PAX8 expression in tubal epithelia: a study of single institution in Japan.

    Science.gov (United States)

    Munakata, Satoru; Yamamoto, Toshiya

    2015-01-01

    Serous ovarian carcinoma is now hypothesized to originate from fallopian tube epithelium (FTE). We investigated the FTE abnormalities in the patients with epithelial ovarian tumors. Our study included 55 cases of serous tumors (24 carcinomas, 8 borderline tumors, and 23 adenomas), 14 mucinous carcinomas, 22 endometrioid carcinomas, 5 clear cell carcinomas, and 2 malignant Brenner tumors. FTE was diagnosed by the diagnostic algorithm, which combines the data of morphology, and p53, Ki-67 immunostaining, as serous tubal intraepithelial carcinoma, serous tubal intraepithelial lesion, p53 signature, and normal/reactive. Serous tubal intraepithelial carcinoma, serous tubal intraepithelial lesion, p53 signature, and normal/reactive were observed in 5, 3, 0, and 16 cases in serous carcinoma; 0, 3, 0, and 5 cases in serous borderline tumor; 0, 1, 1, and 21 cases in serous adenoma; 0, 0, 1, and 13 cases in mucinous carcinoma; 0, 0, 3, and 19 cases in endometrioid carcinoma; 0, 0, 0, and 5 cases in clear cell carcinoma; and 0, 1, 0, and 1 case in malignant Brenner tumor. Among tumors of serous histology and between carcinomas, FTE abnormalities differed significantly (Pcarcinomas were only found in serous carcinoma. The incidence of secretory cell proliferation (SCP) was examined by PAX8 expression. The rate of SCP was extremely high in serous carcinoma (96%). Among tumors of serous histology and between carcinomas, an incidence of SCP differed significantly (Povarian carcinogenesis. The SCP has a meaningful association with serous ovarian cancer.

  9. [Before surgery predictability of malignant ovarian tumors based on ADNEX model and its use in clinical practice].

    Science.gov (United States)

    Joyeux, E; Miras, T; Masquin, I; Duglet, P-E; Astruc, K; Douvier, S

    2016-10-01

    The principal aim of this study was the predictability of malignant ovarian tumors and to determine a cut-off value for this score to indicate the risk of malignancy that would be easy to use in clinical practice. We retrospectively calculated the ADNEX score for all patients who underwent surgery for ovarian tumours in two Burgundy hospitals (Dijon University Hospital and Chalon-sur-Saône Hospital). We used the nine criteria of the ADNEX model. The inclusion criteria were the presence of all of the ADNEX criteria and a histology result. We analysed the sensitivity, specificity, PPV and PNV of four cut-offs (3%, 5%, 10% and 15%) for the entire pool then by age groups; from 14 to 42 (group 1) and 43 and more (group 2) RESULTS: Two hundred and eighty-four patients managed for an ovarian tumour were included between the 1st January 2013 and the 31st December 2015. Our AUC was of 0.94 (95% CI [0.903-0.977]) for discrimination between benign and malignant ovarian tumors. For a cut-off of 10%, sensitivity was 90%, specificity was 81.1%, PPV was 34.6% and PNV 98.5%. Results were lower for young women than for the second group. For a cut-off of 10%, group 1 had a sensitivity of 77.7% and specificity of 89.6%, PPV of 46.6% and PNV 97.5%. For the group 2, sensitivity was 95.2%, specificity was 76.6%, PPV was 33.8% and PNV was 99.2%. The most reasonable cut-off for the whole pool was 10%. For group 1 a cut-off of 5% was retained due to the less satisfying detection of "borderline" tumours more frequent in younger patients. For group 2 the cut-off of 10% gave the best results. In our study, a lower cut-off for younger women seemed better suited to discriminate borderline tumours. In practice, the ADNEX score associated with the peroperative laparoscopic examination seems to be the best way to use the ADNEX model. Our study showed that the ADNEX model allows a good predictability of malignant ovarian tumours. The predictability becomes less satisfying for the youngest patients

  10. [Carcinoid syndrome: report of a case with heart involvement and primary ovarian tumor].

    Science.gov (United States)

    Narváez, R; Viveros, E; Gómez, M; Romero, J; Hernández, S; Dorantes, J; Hernández, P; Rebollar, V; Orea, A; Rodríguez, C; Asensio, E; Oseguera, J

    2001-01-01

    A patient with a primary ovarian carcinoid tumor with extensive carcinoid heart disease, without hepatic metastases is presents. Literature was revisited, emphasizing that carcinoid heart disease secondary to an ovarian tumor is quite rare. Surgical indications relative to this patient are discussed.

  11. Comparison of symptoms and presentation of women with benign, low malignant potential and invasive ovarian tumors

    NARCIS (Netherlands)

    Olsen, C. M.; Cnossen, J.; Green, A. C.; Webb, P. M.

    2007-01-01

    Objectives: To describe symptoms, delay in presentation and reasons for non-presentation among women diagnosed with benign, low malignant potential and malignant ovarian tumors. Methods: Study participants included 457 women who underwent surgery for an ovarian tumor in Queensland, Australia,

  12. Intratumor heterogeneity of morphometric and stereologic variables in primary ovarian tumors and their omental metastatic deposits

    NARCIS (Netherlands)

    Brinkhuis, M.; Scheepstra, C.; Buist, M. R.; van Diest, P. J.; Baak, J. P.

    1997-01-01

    To compare quantitative pathologic variables assessed in primary ovarian tumors and metastatic tumor deposits in the omentum and compare their prognostic value. In 29 cases of advanced ovarian cancer the mean nuclear area (MNA), volume-weighted mean nuclear volume (vv), volume percentage epithelium

  13. Tubal ligation and risk of ovarian cancer subtypes

    DEFF Research Database (Denmark)

    Sieh, Weiva; Salvador, Shannon; McGuire, Valerie

    2013-01-01

    Tubal ligation is a protective factor for ovarian cancer, but it is unknown whether this protection extends to all invasive histological subtypes or borderline tumors. We undertook an international collaborative study to examine the association between tubal ligation and ovarian cancer subtypes....

  14. Isolation and characterization of tumor cells from the ascites of ovarian cancer patients: molecular phenotype of chemoresistant ovarian tumors.

    Directory of Open Access Journals (Sweden)

    Ardian Latifi

    Full Text Available Tumor cells in ascites are a major source of disease recurrence in ovarian cancer patients. In an attempt to identify and profile the population of ascites cells obtained from ovarian cancer patients, a novel method was developed to separate adherent (AD and non-adherent (NAD cells in culture. Twenty-five patients were recruited to this study; 11 chemonaive (CN and 14 chemoresistant (CR. AD cells from both CN and CR patients exhibited mesenchymal morphology with an antigen profile of mesenchymal stem cells and fibroblasts. Conversely, NAD cells had an epithelial morphology with enhanced expression of cancer antigen 125 (CA125, epithelial cell adhesion molecule (EpCAM and cytokeratin 7. NAD cells developed infiltrating tumors and ascites within 12-14 weeks after intraperitoneal (i.p. injections into nude mice, whereas AD cells remained non-tumorigenic for up to 20 weeks. Subsequent comparison of selective epithelial, mesenchymal and cancer stem cell (CSC markers between AD and NAD populations of CN and CR patients demonstrated an enhanced trend in mRNA expression of E-cadherin, EpCAM, STAT3 and Oct4 in the NAD population of CR patients. A similar trend of enhanced mRNA expression of CD44, MMP9 and Oct4 was observed in the AD population of CR patients. Hence, using a novel purification method we demonstrate for the first time a distinct separation of ascites cells into epithelial tumorigenic and mesenchymal non-tumorigenic populations. We also demonstrate that cells from the ascites of CR patients are predominantly epithelial and show a trend towards increased mRNA expression of genes associated with CSCs, compared to cells isolated from the ascites of CN patients. As the tumor cells in the ascites of ovarian cancer patients play a dominant role in disease recurrence, a thorough understanding of the biology of the ascites microenvironment from CR and CN patients is essential for effective therapeutic interventions.

  15. Comprehensive Quantitative Analysis of Ovarian and Breast Cancer Tumor Peptidomes

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Zhe; Wu, Chaochao; Xie, Fang; Slysz, Gordon W.; Tolic, Nikola; Monroe, Matthew E.; Petyuk, Vladislav A.; Payne, Samuel H.; Fujimoto, Grant M.; Moore, Ronald J.; Fillmore, Thomas L.; Schepmoes, Athena A.; Levine, Douglas; Townsend, Reid; Davies, Sherri; Li, Shunqiang; Ellis, Matthew; Boja, Emily; Rivers, Robert; Rodriguez, Henry; Rodland, Karin D.; Liu, Tao; Smith, Richard D.

    2015-01-02

    Aberrant degradation of proteins is associated with many pathological states, including cancers. Mass spectrometric analysis of tumor peptidomes, the intracellular and intercellular products of protein degradation, has the potential to provide biological insights on proteolytic processing in cancer. However, attempts to use the information on these smaller protein degradation products from tumors for biomarker discovery and cancer biology studies have been fairly limited to date, largely due to the lack of effective approaches for robust peptidomics identification and quantification, and the prevalence of confounding factors and biases associated with sample handling and processing. Herein, we have developed an effective and robust analytical platform for comprehensive analyses of tissue peptidomes, which is suitable for high throughput quantitative studies. The reproducibility and coverage of the platform, as well as the suitability of clinical ovarian tumor and patient-derived breast tumor xenograft samples with post-excision delay of up to 60 min before freezing for peptidomics analysis, have been demonstrated. Moreover, our data also show that the peptidomics profiles can effectively separate breast cancer subtypes, reflecting tumor-associated protease activities. Peptidomics complements results obtainable from conventional bottom-up proteomics, and provides insights not readily obtainable from such approaches.

  16. Long-term Behavior of Serous Borderline Tumors Subdivided Into Atypical Proliferative Tumors and Noninvasive Low-grade Carcinomas: A Population-based Clinicopathologic Study of 942 Cases.

    Science.gov (United States)

    Vang, Russell; Hannibal, Charlotte G; Junge, Jette; Frederiksen, Kirsten; Kjaer, Susanne K; Kurman, Robert J

    2017-06-01

    Ovarian serous borderline tumors (SBTs) have been the subject of considerable controversy, particularly with regard to terminology and behavior. It has been proposed that they constitute a heterogenous group of tumors composed, for the most part, of typical SBTs that are benign and designated "atypical proliferative serous tumor (APST)" and a small subset of SBTs with micropapillary architecture that have a poor outcome and are designated "noninvasive low-grade serous carcinoma (niLGSC)". It also has been argued that the difference in behavior between the 2 groups is not due to the subtype of the primary tumor but rather the presence of extraovarian disease, specifically invasive implants. According to the terminology of the 2014 WHO Classification, typical SBTs are equivalent to APSTs and SBTs displaying micropapillary architecture are synonymous with niLGSC. In addition, "invasive implants" were renamed "low-grade serous carcinoma" (LGSC). The argument as to whether it is the appearance of the primary tumor or the presence of extraovarian LGSC that determines outcome remains unsettled. The current study was initiated in 2004 and was designed to determine what factors were predictive of outcome, with special attention to the appearance of the primary tumor (APST vs. niLGSC) and that of the extraovarian disease (noninvasive vs. invasive implants). Our study is population based, involving the entire female population of Denmark. None of the women in the study were lost to follow-up, which ranged up to 36 years (median, 15 y). All the microscopic slides from the contributing hospitals were rereviewed by a panel of 2 pathologists (R.V. and R.J.K.) who were blinded to the follow-up. After excluding those that were not SBTs by the pathology panel, as well as cases with a prior or concurrent cancer or undefined stage, 942 women remained, of which 867 were APSTs and 75 were niLGSCs. The median patient age was 50 years (range, 16 to 97 y). Eight hundred nine women (86

  17. F-18 FDG PET/CT findings of metastatic ovarian tumors from gastrointestinal tract origin.

    Science.gov (United States)

    Park, Hye Lim; Yoo, Ie Ryung; O, Joo Hyun; Han, Eun Ji; Kim, Sung Hoon

    2015-10-01

    To review the F-18 FDG PET/CT findings of metastatic ovarian tumors and to determine any correlation between FDG uptake by metastatic ovarian tumors and that by the primary tumors. PET/CT performed from June 2005 to March 2011 on patients with metastatic ovarian tumors of gastrointestinal tract origin malignancies was analyzed retrospectively. The SUV(max) of metastatic ovarian tumors and primary tumors, when available, was measured. Thirty-two patients were included. Of the 32 cases, 20 had metastatic tumors in bilateral ovaries and 12 had in a single ovary. The mean SUV(max) of the 52 total lesions was 4.1 ± 3.1 (range 1.2-13.3), and 46 lesions showed a heterogeneous FDG uptake pattern. In 22 cases with available primary tumor SUV(max) values, there was a moderate positive correlation with the SUV(max) of the corresponding metastatic tumors (r = 0.559, p = 0.007). There was no significant correlation between the size and SUV(max) of metastatic ovarian tumors (p = 0.128). The mean SUV(max) of metastatic ovarian tumors from colorectal cancers was significantly higher than that of stomach cancers (p = 0.039). Metastatic ovarian tumors showed FDG uptake of variable intensity, depending on the primary tumor type. The FDG uptake pattern was heterogeneous by PET imaging in vast majority of the cases. When the primary tumor demonstrates a low FDG uptake, careful evaluation is necessary since the metastatic ovarian tumors may also show low FDG uptake.

  18. Tumor suppressive effects of bromodomain-containing protein 7 (BRD7) in epithelial ovarian carcinoma.

    Science.gov (United States)

    Park, Young-Ae; Lee, Jeong-Won; Kim, Hye-Sun; Lee, Yoo-Young; Kim, Tae-Joong; Choi, Chel Hun; Choi, Jung-Joo; Jeon, Hye-Kyung; Cho, Young Jae; Ryu, Ji Yoon; Kim, Byoung-Gie; Bae, Duk-Soo

    2014-02-01

    Bromodomain-containing protein 7 (BRD7), which is a subunit of SWI/SNF complex, has been recently suggested as a novel tumor suppressor in several cancers. In this study, we investigated the tumor suppressive effect of BRD7 in epithelial ovarian cancer. We analyzed the expression of BRD7 in human ovarian tissues with real-time PCR. To investigate the functional role of BRD7, we transfected ovarian cancer cells (A2780 and SKOV3) with BRD7 plasmid and checked the cell viability, apoptosis, and invasion. The activities of BRD7 in the signaling pathways associated with carcinogenesis were also tested. In addition, we used the orthotopic mouse model for ovarian cancer to evaluate tumor growth-inhibiting effect by administration of BRD7 plasmid. The BRD7 expression was downregulated in the ovarian cancer tissues compared with normal (P p53-wild) or SKOV3 (p53-null) ovarian cancer cells showed the tumor suppressive effects assessed by cell viability, apoptosis, and invasion assay and especially significantly decreased tumor weight in orthotopic mouse model (A2780). Moreover, we found that tumor suppressive effects of BRD7 are independent to the presence of p53 activity in ovarian cancer cells. BRD7 negatively regulated β-catenin pathway, resulting in decreased its accumulation in the nucleus. These results suggested that BRD7 acts as a tumor suppressor in epithelial ovarian cancers independently of p53 activity, via negative regulation of β-catenin pathway. ©2013 AACR.

  19. MAL2 and tumor protein D52 (TPD52) are frequently overexpressed in ovarian carcinoma, but differentially associated with histological subtype and patient outcome

    International Nuclear Information System (INIS)

    Byrne, Jennifer A; Sutherland, Robert L; Fazio, Anna de; O'Brien, Philippa M; Maleki, Sanaz; Hardy, Jayne R; Gloss, Brian S; Murali, Rajmohan; Scurry, James P; Fanayan, Susan; Emmanuel, Catherine; Hacker, Neville F

    2010-01-01

    The four-transmembrane MAL2 protein is frequently overexpressed in breast carcinoma, and MAL2 overexpression is associated with gain of the corresponding locus at chromosome 8q24.12. Independent expression microarray studies predict MAL2 overexpression in ovarian carcinoma, but these had remained unconfirmed. MAL2 binds tumor protein D52 (TPD52), which is frequently overexpressed in ovarian carcinoma, but the clinical significance of MAL2 and TPD52 overexpression was unknown. Immunohistochemical analyses of MAL2 and TPD52 expression were performed using tissue microarray sections including benign, borderline and malignant epithelial ovarian tumours. Inmmunohistochemical staining intensity and distribution was assessed both visually and digitally. MAL2 and TPD52 were significantly overexpressed in high-grade serous carcinomas compared with serous borderline tumours. MAL2 expression was highest in serous carcinomas relative to other histological subtypes, whereas TPD52 expression was highest in clear cell carcinomas. MAL2 expression was not related to patient survival, however high-level TPD52 staining was significantly associated with improved overall survival in patients with stage III serous ovarian carcinoma (log-rank test, p < 0.001; n = 124) and was an independent predictor of survival in the overall carcinoma cohort (hazard ratio (HR), 0.498; 95% confidence interval (CI), 0.34-0.728; p < 0.001; n = 221), and in serous carcinomas (HR, 0.440; 95% CI, 0.294-0.658; p < 0.001; n = 182). MAL2 is frequently overexpressed in ovarian carcinoma, and TPD52 overexpression is a favourable independent prognostic marker of potential value in the management of ovarian carcinoma patients

  20. CHARACTERISTICS OF CLINICAL COURSE OF METASTATIC AND PRIMARY OVARIAN TUMORS IN COLON CANCER

    Directory of Open Access Journals (Sweden)

    I. A. Dzhanyan

    2015-01-01

    Full Text Available The aim of this study was to investigate clinical pecuiliarities of ovarian tumors in colon cancer patients and determination of complex diagnostic methods.Subject and methods. Russian N.N.  Blokhin Cancer Research Center archives were used for retrospective study, patients, who underwent treatment during 1989–2013  were included. Colon cancer patients with ovarian metastases and with synchronous or metachronous tumors were included.Results. 141 patients were included: 91 patients had colon cancer with ovarian metastases (group 1 and 50 patients had synchronous or metachronous ovarian tumours (group 2. Ovarian tumors were diagnosed during the 1 year in 74 (81.3 % patients in group 1 and in 23 (46 % in group 2. Patients in group 2 less frequently had children (9 (18.0 % vs 5 (5.5 + 2.3 %, р < 0.05, family history of cancer (3 (6 % vs 16 (17.6 %, р < 0.05 and concomitant diseases. Median CA 125 level in group 1 was 64.96 ng/ml and 180 ng/ml in group 2. Ovarian tumors had solid and cystic structure during US examination in 66 (73 % patients in group 1 and 31 (62 % patients in group 2 had solid ovarian tumors on US examination.Conclusions. The differential diagnostics of primary and metastatic ovarian tumors must include CEA, CA 19–9 and CA 125 serum levels and pelvic US.

  1. The Role of Hypoxia in the Tumor Microenvironment: Implications for Ovarian Cancer Therapy

    Science.gov (United States)

    2017-07-01

    kit (Rankin et al., 2012). Tumor sections will be stained and quantified for CD31, an endothelial cell marker . The number of CD31 positive vessels...AWARD NUMBER: W81XWH-15-1-0097 TITLE: The Role of Hypoxia in the Tumor Microenvironment: Implications for Ovarian Cancer Therapy PRINCIPAL...SUBTITLE 5a. CONTRACT NUMBER 0097W81XW 0097The Role of Hypoxia in the Tumor Microenvironment: Implications for Ovarian Cancer Therapy

  2. Alternative tumor markers in the diagnosis of ovarian cancer.

    Science.gov (United States)

    Karakaya, Burcu Kısa; Başer, Eralp; Bildacı, Berk; Cömert, Esra Çabuk; Bayraktar, Nilufer; Dursun, Polat; Kuşçu, Esra; Ayhan, Ali

    2016-01-01

    The aim of the study was to assess the usefulness of various tumor markers (CA125, HE4, bcl2) measured in serum, urine and saliva in the differential diagnosis of adnexal masses. Our study was conducted at the Başkent University Medical School, Department of Obstetrics and Gynecology, Ankara, Turkey, between November 2010 and March 2011. Fifty patients with a suspicion of malignant adnexal mass and 30 controls were included in the study. Serum and urine CA-125, HE4, and bcl2 levels were evaluated for their role in the diagnosis of epithelial ovarian cancer (EOC). Serum CA-125 and HE4 levels, and urine HE4 levels were significantly higher in malignant cases as compared to controls (p saliva and urine were similar in malignant cases and controls (p > 0.05). We demonstrated that serum CA125, serum HE4 and urine HE4 levels were elevated in patients with ovarian cancer. These findings should be assessed in future studies with larger sample sizes in order to reach more definite conclusions.

  3. The accuracy of CT and tumor markers in the detection of a recurrent ovarian carcinoma

    International Nuclear Information System (INIS)

    Wakabayashi, Yukari; Ishida, Jiro; Kotake, Fumio; Hirose, Masahiro; Kawana, Koji; Abe, Kimihiko; Amino, Saburo; Negishi, Yoshiyuki; Akiya, Kiyoshi

    1989-01-01

    Twenty-three patients previously diagnosed as having ovarian cancer were examined with both serum tumor markers (CA 125, CA 19-9, TPA, IAP, AFP) and a pelvic CT scan. The tumor markers predict the clinical outcome more accurately than the CT scan. Further, the tumor markers showed a clear correlation with the clinical course. But in one case, however, the tumor markers were seen to reduce below the normal level from chemotherapy, while the CT scan showed a tumor mass. Thus, both, a CT scan and tumor marker assays are felt to be indispensable for detecting the recurrence of an ovarian cancer. (author)

  4. Ovarian Carcinoma During Pregnancy:Report of Two Cases

    Directory of Open Access Journals (Sweden)

    Ertan Akpınar

    2006-04-01

    Full Text Available Ovarian tumors during pregnancy are rare events. Although the majority of ovarian tumors complicating pregnancy are benign, they are still important because of the difficulty in differentiating between benign and malign tumors. In most cases, tumors are detected accidentally during routine examination, ultrasound or a caesarean section at term. An ovarian malignancy occuring in association with pregnancy is rare accounting for only 2-5% of ovarian tumors discov ered during pregnancy. Histologic subtypes and prognosis do not differ f rom tumors not associated with pregnancy, it seems howev er, that there are more lesions of borderline malignancy and of low grade. Two cases of pregnancy associated malignant ov arian tumors, one mucinous cystadenocarcinoma and one endometrioid carcinoma are reported. Patient with mucinous cystadenocarcinoma had a history of persistent ovarian tumors during her two pregnancy.

  5. Tumor uptake of intravenously administered radiolabeled antibodies in ovarian carcinoma patients in relation to antigen expression and other tumor characteristics

    NARCIS (Netherlands)

    Buist, M. R.; Kenemans, P.; Molthoff, C. F.; Roos, J. C.; den Hollander, W.; Brinkhuis, M.; Baak, J. P.

    1995-01-01

    To study factors that possibly influence the heterogeneous tumor uptake of radiolabeled antibodies, tissues from 34 ovarian-carcinoma patients were obtained 2 to 8 days after i.v. injection with radiolabeled murine OV-TL3 or chimeric MOv18 (cMOv18). The tumor uptake and the ratio of tumor to normal

  6. Effects of adjuvant radiotherapy on borderline and malignant phyllodes tumors: A systematic review and meta-analysis

    Science.gov (United States)

    ZENG, SHIYAN; ZHANG, XINDAN; YANG, DEJUAN; WANG, XIAOYI; REN, GUOSHENG

    2015-01-01

    The standard treatment for borderline and malignant phyllodes tumors is wide local excision (margins ≥1 cm), in the context of either breast-conserving surgery (BCS) or total mastectomy (TM). Due to the high risk of local recurrence (LR) following surgical intervention alone, the addition of adjuvant radiotherapy (RT) has been previously investigated; however, the conclusions have been inconsistent. This systematic review and meta-analysis was designed to assess the efficacy of adjuvant RT for borderline and malignant phyllodes tumors. Pubmed and Web of Science were systematically searched to identify relevant studies assessing the effect of adjuvant RT on borderline and malignant phyllodes tumors from the inception of this technique through May, 2014. A total of 8 studies were identified among 332 citations. In this meta-analysis, patients who received adjuvant RT had a lower relative risk of LR [hazard ratio (HR) = 0.43, 95% confidence interval (CI): 0.23–0.64]. The absolute risk difference was 10.1% (95% CI: 4.9–17.6), corresponding to a number needed to treat of 10. Our pooled meta-analysis clearly demonstrated a decreased risk of LR in patients with borderline and malignant phyllodes tumors who received RT following BCS (HR=0.31, 95% CI: −0.10–0.72). However, the combined HR for LR in the TM group did not demonstrate that adjuvant RT was superior to no RT (HR=0.68, 95% CI: −0.28–1.64). No significant differences were observed in overall survival (OS) or disease-free survival (DFS) between the two groups. Our analysis suggested that adjuvant RT for borderline and malignant phyllodes tumors decreased the LR rate in patients undergoing BCS. However, adjuvant RT was not found to exert an effect on OS or DFS. PMID:26137284

  7. New sonographic morphology score for the differentiation of malignant from benign ovarian tumors.

    Science.gov (United States)

    Shen, Zhi Yong; He, Ai Qin; Xia, Gan Lin; Wu, Ming Feng; Li, Jun; Ding, Yong Sheng

    2016-08-01

    The aim of this study was to explore the efficacy of a new sonographic morphology score (SMS) to differentiate malignant from benign ovarian tumors. Data on 84 ovarian tumors in patients hospitalized in our hospital between 2013 and 2014 were retrospectively analyzed. We established a new sonographic morphology score for ovarian tumors based on volume and structure scores. The efficacy of the new SMS was compared with that of Ueland's index (the old SMS). Receiver-operator curves (ROC) of the two SMS were constructed, and the areas under the curve were calculated and compared. The ROC of the new SMS was also compared with those for the patients' CA-125 and CA-72-4 levels. The area under the ROC of the new SMS for ovarian tumors was 0.836, while for the old SMS for ovarian tumors it was 0.709. By Z-test (Z = 2.452, P = 0.0384), there was a significant difference between the new SMS and the old SMS in the diagnosis of ovarian tumors. There was no significant difference in the area under the ROC between the new SMS and CA-125 and CA-72-4 in the diagnosis of ovarian tumors. With a cut-off value of 6, the sensitivity, specificity, positive prognostic value, and negative prognostic value of the new SMS were 0.797, 0.85, 0.944, and 0.567, respectively. The new SMS may be used to differentiate malignant ovarian carcinomas from benign tumors except in the case of ovarian thecoma. © 2016 Japan Society of Obstetrics and Gynecology.

  8. The anti-tumor effects and molecular mechanisms of suberoylanilide hydroxamic acid (SAHA on the aggressive phenotypes of ovarian carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Shuo Chen

    Full Text Available Histone deacetylase inhibitors (HDACi, such as suberoylanilide hydroxamic acid (SAHA, have been shown to act selectively on gene expression, and are potent inducers of growth arrest, differentiation and apoptosis in various types of cancers in vitro and in vivo. This study aimed to elucidate the anti-tumor effects and molecular mechanisms of SAHA on the aggressive phenotypes of ovarian carcinoma. Two pairs of cell lines (SKOV3 and SKOV3/DDP; HO8910 and HO8910-PM were exposed to SAHA treatment, and the effects on acetyl-Histone H3 and H4 expression levels were analyzed and compared against the aggressive behaviors of ovarian carcinoma. Our results showed that SAHA suppressed proliferation in both a concentration- and time-dependent manner in all four cell lines; induced S/G2 arrest in SKOV3 and SKOV3/DDP cells; and conversely, induced G1 arrest in HO8910 and HO8910-PM cells. SAHA treatment induced apoptosis and reduced migration, invasion and lamellipodia formation in the ovarian carcinoma cells; furthermore, SAHA decreased expression of Cyclin B1 and CDC2P34 mRNA, and downregulated CDC2P34, Erk1/2, CyclinB1 and MMP-9 proteins. In contrast, SAHA increased expression of Caspase-3, p21 and p53 mRNA, and upregulated acetyl-Histones H3 and H4, Caspase-8, and p53 proteins. Basal acetylation of histone H3 and H4 was higher in ovarian carcinoma compared to normal ovarian tissues and benign ovarian tumors, and in borderline tumor than in normal ovarian tissues, and was positively correlated with differentiation and expression of the proliferative marker, Ki-67 (P < 0.05. We suggest that SAHA may suppress growth, migration and invasion in ovarian carcinoma cells, including cisplatin-resistant or highly-invasive ovarian cells, by promoting histone acetylation and modulating their phenotype-related molecules. As such, aberrant acetylation of histone H3 and H4 may play an important role in the carcinogenesis and differentiation of ovarian carcinoma.

  9. Early Alterations in Ovarian Surface Epithelial Cells and Induction of Ovarian Epithelial Tumors Triggered by Loss of FSH Receptor

    Directory of Open Access Journals (Sweden)

    Xinlei Chen

    2007-06-01

    Full Text Available Little is known about the behavior of the ovarian surface epithelium (OSE, which plays a central role in ovarian cancer etiology. It has been suggested that incessant ovulation causes OSE changes leading to transformation and that high gonadotropin levels during postmenopause activate OSE receptors, inducing proliferation. We examined the chronology of OSE changes, including tumor appearance, in a mouse model where ovulation never occurs due to deletion of follitropin receptor. Changes in epithelial cells were marked by pan-cytokeratin (CK staining. Histologic changes and CK staining in the OSE increased from postnatal day 2. CK staining was observed inside the ovary by 24 days and increased thereafter in tumor-bearing animals. Ovaries from a third of aged (1 year mutant mice showed CK deep inside, indicating cell migration. These tumors resembled serous papillary adenoma of human ovaries. Weak expression of GATA-4 and elevation of PCNA, cyclooxygenase-1, cyclooxygenase-2, and plateletderived growth factor receptors α and β in mutants indicated differences in cell proliferation, differentiation, and inflammation. Thus, we report that OSE changes occur long before epithelial tumors appear in FORKO mice. Our results suggest that neither incessant ovulation nor follicle-stimulating hormone receptor presence in the OSE is required for inducing ovarian tumors; thus, other mechanisms must contribute to ovarian tumorigenesis.

  10. Gonadotropins and female sex steroid hormones in cyst fluid and serum from patients with ovarian tumors.

    NARCIS (Netherlands)

    Thomas, C.M.G.; Boss, E.A.; Boonstra, H.; Tienoven, D. van; Sweep, C.G.J.; Massuger, L.F.A.G.

    2008-01-01

    The objective of the present study was to determine the concentrations of LH, FSH, 17beta-estradiol and progesterone in ovarian cyst fluid and serum from patients with benign and malignant ovarian tumors and to assess the correlation of the gonadotropin and female sex steroid hormone concentrations

  11. Cancer-testis antigen expression is shared between epithelial ovarian cancer tumors.

    Science.gov (United States)

    Garcia-Soto, Arlene E; Schreiber, Taylor; Strbo, Natasa; Ganjei-Azar, Parvin; Miao, Feng; Koru-Sengul, Tulay; Simpkins, Fiona; Nieves-Neira, Wilberto; Lucci, Joseph; Podack, Eckhard R

    2017-06-01

    Cancer-testis (CT) antigens have been proposed as potential targets for cancer immunotherapy. Our objective was to evaluate the expression of a panel of CT antigens in epithelial ovarian cancer (EOC) tumor specimens, and to determine if antigen sharing occurs between tumors. RNA was isolated from EOC tumor specimens, EOC cell lines and benign ovarian tissue specimens. Real time-PCR analysis was performed to determine the expression level of 20 CT antigens. A total of 62 EOC specimens, 8 ovarian cancer cell lines and 3 benign ovarian tissues were evaluated for CT antigen expression. The majority of the specimens were: high grade (62%), serous (68%) and advanced stage (74%). 58 (95%) of the EOC tumors analyzed expressed at least one of the CT antigens evaluated. The mean number of CT antigen expressed was 4.5 (0-17). The most frequently expressed CT antigen was MAGE A4 (65%). Antigen sharing analysis showed the following: 9 tumors shared only one antigen with 62% of the evaluated specimens, while 37 tumors shared 4 or more antigens with 82%. 5 tumors expressed over 10 CT antigens, which were shared with 90% of the tumor panel. CT antigens are expressed in 95% of EOC tumor specimens. However, not a single antigen was universally expressed across all samples. The degree of antigen sharing between tumors increased with the total number of antigens expressed. These data suggest a multi-epitope approach for development of immunotherapy for ovarian cancer treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Comparison of stromal CD10 expression in benign, borderline, and malignant phyllodes tumors among Egyptian female patients

    Directory of Open Access Journals (Sweden)

    Wael S Ibrahim

    2011-01-01

    Full Text Available Background: Phyllodes tumors are group of biphasic fibroepithelial tumors of the breast of varying malignant potential, ranging from benign tumors to fully malignant sarcomas. According to the Egyptian National Cancer Institute, female malignant cases showed appreciable increase in the recent time period for breast cancer with the malignant phyllodes tumors representing 0.41% of cases in the year 2003-2004. Aims: This is an immunohistochemical study to compare CD10 expression in benign, borderline, and malignant phyllodes tumors, in order to highlight its diagnostic and prognostic values. Materials and Methods: This study conducted 34 Egyptian female cases of phyllodes tumors of different grades to be studied histologically and immunohistochemically using antibodies against CD10. Statistical Analysis: The Chi-square test was used to determine differences in CD10 expression between benign, borderline, and malignant tumors. One-way ANOVA test was used to determine whether the difference was significant. Significance was established at P<0.05. Results: In the 24 cases of benign phyllodes tumors, only four cases (16.7% showed positive CD10 reactivity. Three cases (60% out of five borderline phyllodes tumors showed positive CD10 reactivity, while four (80% out of five cases of malignant phyllodes tumors showed positive CD10 staining. Conclusion: From these highly significant results, we believe that there is a strong correlation between CD10 expression and tumor grade, which could be an important observation that may have both diagnostic and prognostic implications as well as promising potential target for development of novel therapies.

  13. Eliciting Autoimmunity to Ovarian Tumors in Mice by Genetic Disruption of T Cell Tolerance Mechanisms

    National Research Council Canada - National Science Library

    Nelson, Brad H

    2005-01-01

    ... mechanisms will likely be identified in future. We hypothesize that ovarian tumors are recognized in an antigen-specific manner by T cells but induce immunologic tolerance through one or more of these homeostatic mechanisms, which have evolved...

  14. Locomotor proteins in tissues of primary tumors and metastases of ovarian and breast cancer

    Science.gov (United States)

    Kondakova, I. V.; Yunusova, N. V.; Spirina, L. V.; Shashova, E. E.; Kolegova, E. S.; Kolomiets, L. A.; Slonimskaya, E. M.; Villert, A. B.

    2016-08-01

    The paper discusses the capability for active movement in an extracellular matrix, wherein remodeling of the cytoskeleton by actin binding proteins plays a significant role in metastases formation. We studied the expression of actin binding proteins and β-catenin in tissues of primary tumors and metastases of ovarian and breast cancer. Contents of p45 Ser β-catenin and the actin severing protein gelsolin were decreased in metastases of ovarian cancer relative to primary tumors. The level of the cofilin, functionally similar to gelsolin, was significantly higher in metastases compared to primary ovarian and breast tumor tissue. In breast cancer, significant increase in the number of an actin monomer binder protein thymosin-β4 was observed in metastases as compared to primary tumors. The data obtained suggest the involvement of locomotor proteins in metastases formation in ovarian and breast cancer.

  15. Laparoscopic adnexectomy with peritonectomy for an ovarian tumor adhered to the pelvic sidewall.

    Science.gov (United States)

    Kobayashi, Eiji; Kanao, Hiroyuki; Andou, Masaaki

    2013-01-01

    Laparoscopic adnexectomy is one of the most commonly used surgical techniques for the treatment of ovarian tumor. However, many physicians find it difficult to conduct the resection without rupturing the ovarian tumor, especially in cases with tumor adhesions. In the case we are presenting, we unexpectedly encountered an ovarian tumor adherent to the pelvic sidewall. Because the possibility of a malignancy could not be completely excluded, we decided to concomitantly resect the ovary and its adherent peritoneum, to avoid any potential tumor rupture due to its manipulation. We were successfully able to laparoscopically retrieve the intact ovarian tumor, without its rupture. The pathological diagnosis was of a Grade 2, FIGO stage IIb endometrioid adenocarcinoma of both ovaries. As a result of this diagnosis, we performed a comprehensive staging laparoscopy. Following the completion of adjuvant chemotherapy, the patient has showed no signs of recurrent malignancy after 3 years. This case report describes our technique for the surgical management of an ovarian tumor adherent to the pelvic wall. To avoid spillage of the tumor contents, the simultaneous resection of the tumor with its adhered peritoneum is a useful method to consider. Copyright © 2013 S. Karger AG, Basel.

  16. Prognostic significance of cytosolic pS2 content in ovarian tumors

    International Nuclear Information System (INIS)

    Raigoso, P.; Allende, T.; Zeidan, N.; Llana, B.; Bernardo, L.; Roiz, C.; Tejuca, S.; Vazquez, J.; Lamelas, M.L.

    2002-01-01

    Aim: pS2 is an estrogen regulated peptide which has been associated with a good prognosis an with a more favorable response to treatment in breast cancer patients. In ovarian tumors, the expression of pS2 was demonstrated at both mRNA and protein levels. In addition, it has been showed significant association of pS2 with mucinous differentiation or well differentiation grade of the tumors. However, it is little know about the prognostic significance of the pS2 content in ovarian carcinomas. The aims of the present work were to analyze the cytosolic pS2 content in benign and malignant ovarian tumors, its relationship with clinico-pathologic parameters, steroid receptor status, and prognostic significance. Material and Methods: We analysed the cytosolic concentrations of pS2 in 91 specimen ovarian tissues by an immunoradiometric assay (ELSA-pS2, CIS, France). The tissues were 8 normal ovaries, 43 benign tumors and 40 malignant ovarian tumors. The same ovarian tissues processed to pS2 were analyzed to Estrogen (ER) and Progesterone (PgR) Receptor status. These steroid receptors were quantified biochemically following commercial ELISA method (ABBOTT Diagnostics, Germany). The relationship between cytosolic content and clinico-pathologic factors was examined by the Mann-Whitney or Kruskall-Wallis test. Correlation between steroid receptors and pS2 content was calculated with the Spearman test. Survival curves were calculated using the Kaplan-Meier method and compared by the log-rank test. Differences were considered significant at 5% probability level. Results: pS2 could be detected in 30 cases (32.9%) with values ranged from 0.04 to 89 ng/mg prt. Only one normal ovary showed detectable levels of pS2 and there were not differences in cytosolic content between benign and malignant ovarian tumors. The pS2 levels were only associated to mucinous differentiation in both benign and malignant ovarian tumors (p=0.029 and p=0.015, respectively). Significantly higher

  17. Distribution of Microsatellite instability in Danish ovarian tumor patients and the prognostic value in ovarian cancer patients

    DEFF Research Database (Denmark)

    Begum, F.D.; Kjaer, S.K.; Blaakaer, J.

    2008-01-01

    The repeated frequency of microsatellite instability (MSI) in ovarian cancer (OC) ranges from 0% to 50%. Most MSI studies including OC patients have involved relatively small number of tumors, a wide range of different MSI markers, different patient characteristics, and varying criteria for defin...

  18. FGF18 as a potential biomarker in serous and mucinous ovarian tumors.

    Science.gov (United States)

    El-Gendi, Saba; Abdelzaher, Eman; Mostafa, Mohamed Farouk; Sheasha, Ghada Abu

    2016-03-01

    Fibroblast growth factor 18 (FGF18) has been suggested to play important roles in promoting progression of ovarian high-grade serous carcinoma. Our aim was to investigate FGF18 expression in the whole spectrum of serous and mucinous ovarian tumors, highlighting differences in expression within the adenoma-carcinoma sequence and differences between type I and type II tumors. We also aimed to test the prognostic significance of this expression and its relation to microvessel density (MVD). We evaluated the immunohistochemical expression of FGF18 and CD31 in 103 ovarian tumors and statistically analyzed their association with clinicopathological variables and patients' outcome. FGF18 score increased significantly within the adenoma-carcinoma sequence for serous and mucinous tumors. MVD increased significantly only among serous tumors. FGF18 and MVD correlated significantly (overall and among serous tumors only) and were significantly higher in type II than type I tumors. Cox regression models were built. Independent predictors could not be determined due to multicollinearity between the predictors. However, the combination of International Federation of Gynecology and Obstetrics (FIGO) stage, ovarian carcinoma type, and/or FGF18 score achieved the highest predictability of poor prognosis. FGF18 could play a role within the adenoma-carcinoma sequence in type I tumors and might modulate angiogenesis among serous tumors. Our findings further augment the differences between type I and type II tumors. The combination of FIGO stage, ovarian carcinoma type, and/or FGF18 score could predict poor prognosis among ovarian carcinoma patients. Our work identifies FGF18 in ovarian neoplasia as a promising field of research, although evaluation of the performance of the developed models is still needed.

  19. Diagnosis of ovarian tumors by ultrasonography and x-ray CT

    International Nuclear Information System (INIS)

    Watanabe, Hiromu

    1986-01-01

    A drawback in ultrasonography, an indispensable technique in imaging ovarian malignancies, is that it sometimes shows false positive for benign tumors including dermoid cyst and ovarian endometriosis. To overcome this, the concurrent use of X-Ray CT seems warrantable and this led us to carry out the study summarized below. CT was carried out on 268 of 322 ovarian disease cases which had undergone ultrasonography. The results obtained were as follows. Sensitivity of ultrasonography and CT in ovarian malignancies were 82 % and 88 % respectively. Of the cases subjected to both techniques, those who were deemed false positive were 39 in ultrasonography and 12 in CT. Ultrasonographic imagings of dermoid cyst and ovarian endometriosis were classified on the basis of their patterns. The results obtained revealed that those in which it was difficult to discriminate the image from ovarian malignancy were types V and VI in dermoid cyst and type III-C in ovarian endometriosis. In both dermoid cyst and ovarian endometriosis, nearly a 100 % accuracy rate was obtainable with CT for diagnosis of benign tumors. This strongly suggested that concurrent use of CT was required, in diagnosing ovarian diseases with the V or VI and III-C patterns referred to above. (author)

  20. Serum tumor marker CA 125 for monitoring ovarian cancer during follow-up

    DEFF Research Database (Denmark)

    Tuxen, Malgorzata K.; Sölétormos, G; Dombernowsky, P

    2002-01-01

    CA 125 is currently widely applied in the management of patients with ovarian cancer. However, a change in results of CA 125, which should be considered significant, has not been defined. The aim of this study was to investigate the ability of CA 125 to signal progressive ovarian cancer during fo...... utility of serological tumor markers in patients with ovarian cancer.......CA 125 is currently widely applied in the management of patients with ovarian cancer. However, a change in results of CA 125, which should be considered significant, has not been defined. The aim of this study was to investigate the ability of CA 125 to signal progressive ovarian cancer during...... follow-up after first-line chemotherapy. The study patients were selected retrospectively among 255 patients with stage IC-IV ovarian cancer. The evaluation of the CA 125 information was based on the analytical imprecision, the normal intra-individual biological variation, the sampling interval...

  1. A Case of a Giant Borderline Phyllodes Tumor Early in Pregnancy Treated with Mastectomy and Immediate Breast Reconstruction.

    Science.gov (United States)

    Gentile, Lori F; Gaillard, William Foster; Wallace, Jodi-Ann; Spiguel, Lisa R P; Alizadeh, Layla; Lentz, Ashley; Shaw, Christiana

    2016-11-01

    Breast tumors in pregnancy are often times diagnosed at advanced stages secondary to difficulty distinguishing between pathologic from normal physiologic changes. Often benign, phyllodes tumors are rare fibroepithelial stromal tumors of the breast, most commonly diagnosed in the 4th and 5th decades of life. However, these tumors may be characterized by malignancy with metastases in 10% of cases. In this paper, we report a novel case of a young woman presenting at 8 weeks gestation with a large borderline phyllodes tumor. An exceedingly rare condition, with only nine previously reported cases, phyllodes tumors in pregnancy frequently display more aggressive characteristics with larger median tumor size, more malignant potential, and more rapid growth rate. Here, we describe our experience safely and effectively treating this rare condition in a young gravid women with mastectomy and immediate breast reconstruction in the second trimester. © 2016 Wiley Periodicals, Inc.

  2. Tumor-infiltrating Cytotoxic T Lymphocytes as Independent Prognostic Factor in Epithelial Ovarian Cancer With Wilms Tumor Protein 1 Overexpression

    NARCIS (Netherlands)

    Vermeij, Renee; de Bock, Geertruida H.; Leffers, Ninke; ten Hoor, Klaske A.; Schulze, Ute; Hollema, Harry; van der Burg, Sjoerd H.; van der Zee, Ate G. J.; Daemen, Toos; Nijman, Hans W.

    2011-01-01

    Immune response characterization at the primary tumor site enables the design of therapeutic vaccination strategies with higher efficacy in epithelial ovarian cancer (EOC). In this study, we related Wilms tumor protein 1 (WT1) overexpression, a well-established immunotherapeutic target, to

  3. Coexistence of tuberculous axillary lymphadenitis and giant borderline malignant phyllodes tumor of the breast: A rare case report

    Directory of Open Access Journals (Sweden)

    Sunder Goyal

    2015-04-01

    Full Text Available Cystosarcoma phyllodes are uncommon breast tumors which rarely metastasize to axillary lymph nodes. The tumor is similar to fibroadenoma in structure, but it is different histologically. Although surgery (excision vs. mastectomy is the mainstay of treatment, the need for adjuvant therapies such as radiotherapy for a malignant variety is unclear. Its association with ipsilateral tubercular axillary lymph nodes has not been reported in literature so far. We report a 35-year-old female that presented with a giant borderline malignant phyllodes tumor of the right breast along with ipsilateral tubercular granulomatous axillary lymph nodes. [Arch Clin Exp Surg 2015; 4(2.000: 114-117

  4. Imbalances of Chromosomes 4, 9, and 12 are Recurrent in the Thecoma-Fibroma Group of Ovarian Stromal Tumors

    OpenAIRE

    Streblow, Renae C.; Dafferner, Alicia J.; Nelson, Marilu; Fletcher, Mavis; West, William W.; Stevens, Rachel K.; Gatalica, Zoran; Novak, Deborah; Bridge, Julia A.

    2007-01-01

    Traditional cytogenetic studies of ovarian stromal tumors are few, although trisomy 12 has been frequently documented utilizing fluorescence in-situ hybridization (FISH). In the current study, karyotypic analysis of four ovarian stromal tumors and a review of the literature suggested that numerical abnormalities of chromosomes 4 and 9 might also be important, possibly as secondary changes. To determine the frequency of 4, 9, and 12 aneuploidy in a larger group of ovarian tumors, FISH studies ...

  5. A survey of DICER1 hotspot mutations in ovarian and testicular sex cord-stromal tumors.

    Science.gov (United States)

    Conlon, Niamh; Schultheis, Anne M; Piscuoglio, Salvatore; Silva, Annacarolina; Guerra, Esther; Tornos, Carmen; Reuter, Victor E; Soslow, Robert A; Young, Robert H; Oliva, Esther; Weigelt, Britta

    2015-12-01

    Sertoli-Leydig cell tumors are characterized by the presence of somatic DICER1 hotspot mutations. In this study, we sought to define the association between DICER1 hotspot mutations and different morphologic subtypes of ovarian Sertoli-Leydig cell tumors. Furthermore, we aimed to assess whether DICER1 hotspot mutations occur in other ovarian sex cord-stromal tumors, testicular sex cord-stromal tumors, or other female genital tract tumors with rhabdomyosarcomatous differentiation. We subjected a series of ovarian Sertoli-Leydig cell tumors (n=32), Sertoli cell tumors (n=5) and gynandroblastomas (n=5), testicular sex cord-stromal tumors (n=15) and a diverse group of female genital tract tumors with rhabdomyosarcomatous morphology (n=10) to DICER1 hotspot mutation analysis using Sanger sequencing. We also tested two gynandroblastomas for the presence of FOXL2 hotspot mutations (p.C134W; c.402C>G). Twenty of 32 (63%) Sertoli-Leydig cell tumors harbored a DICER1 hotspot mutation, of which 80% had the p.E1705K mutation. No association was found between DICER1 mutation status and the presence of heterologous or retiform differentiation in Sertoli-Leydig cell tumors. DICER1 mutations were found at similar frequencies in gynandroblastoma (2/5; 40%) and ovarian Sertoli cell tumors (5/8; 63%; P>0.1), and all mutated tumors harbored a p.E1705K mutation. DICER1 hotspot mutations were also identified in a single cervical rhabdomyosarcoma and in the rhabdomyosarcomatous component of a uterine carcinosarcoma. No DICER1 mutations were detected in testicular sex cord-stromal tumors. Two DICER1 wild-type gynandroblastomas harbored a p.C134W FOXL2 hotspot mutation in both tumor components. In this study we confirmed that DICER1 hotspot mutations occur in over half of ovarian Sertoli-Leydig cell tumors, and are unrelated to tumor differentiation. We also widened the spectrum of ovarian sex cord-stromal tumors with sertoliform differentiation, in which DICER1 mutations are known to

  6. HER-2 amplification but not butyrylcholinesterase multability reflects aggressiveness of European-originated ovarian tumors.

    Science.gov (United States)

    Dobianer, K; Hruza, C; Ehrlich, G; Sevelda, P; Czerwenka, K; Soreq, H; Spona, J; Zakut, H

    1995-02-01

    Tumorigenic roles were variably suggested for HER-2 and INT-2 oncogene amplifications and the "atypical" aspartate to glycine mutability in the butyrylcholinesterase (BCHE) gene in ovarian adenocarcinomas. To examine this notion we searched for correlations between these three phenomena and ovarian tumor classification and aggressiveness, using quantitative polymerase chain reaction (PCR), single-strand conformation polymorphism (SSCP), and direct PCR sequencing. Our findings revealed no alleles carrying the atypical BCHE mutability in 30 European-originated patients with ovarian tumors compared with 11% (2/18) such alleles in Israeli patients with malignant ovarian tumors. This apparently reflected population diversity rather than disease relationship. INT-2 amplification was observed in 14/94 (15%) of the European patients; however, there was no correlation between this phenomenon and clinicopathological indices in the corresponding patients. In contrast, in 94 tumor samples we found that 40% (38/94) of the cases had HER-2 amplification. Moreover, there was a highly significant correlation (P < 0.008) between the over fivefold HER-2 amplification and ovarian tumor severity. These findings demonstrate an informative value for HER-2 amplification tests in tumor DNA, but not for INT-2 amplification or BCHE mutability, for the assessment of treatment.

  7. Primary ovarian neuroendocrine tumor arising in association with a mature cystic teratoma: A case report

    Directory of Open Access Journals (Sweden)

    Nicolas M. Orsi

    2016-08-01

    Full Text Available Primary ovarian carcinoid tumors are exceptionally rare entities accounting for approximately 0.1% of all ovarian neoplasms. This report describes a primary ovarian neuroendocrine tumor arising in association with a mature cystic teratoma in a 65 year-old woman. Macroscopically, the unilateral adnexal tumor was composed of cystic, solid and mucinous elements which resolved into a dual component lesion histologically. The majority of the tumor displayed an organoid architecture with mild to moderate pleomorphism and no discernible mitotic activity, while approximately 10% consisted of sheets and groups of cells with highly pleomorphic nuclei, necrosis and occasional mitoses. Features of a mature cystic teratoma were seen very focally. Immunohistochemistry revealed strong, diffuse positivity for CD56 and synaptophysin. Chromogranin immunonegativity was noted and there was an absence of nuclear β-catenin accumulation. Ki-67 index was 10–12%. Although there is no established diagnostic framework for primary ovarian carcinoid tumors, this case was diagnosed as a well-differentiated neuroendocrine tumor, Grade 2 (intermediate grade, arising in association with a mature cystic teratoma/dermoid cyst. This case highlights the need to develop ovarian diagnostic criteria in this area.

  8. Ovarian Cancers: Genetic Abnormalities, Tumor Heterogeneity and Progression, Clonal Evolution and Cancer Stem Cells

    Science.gov (United States)

    Castelli, Germana; Pelosi, Elvira

    2018-01-01

    Four main histological subtypes of ovarian cancer exist: serous (the most frequent), endometrioid, mucinous and clear cell; in each subtype, low and high grade. The large majority of ovarian cancers are diagnosed as high-grade serous ovarian cancers (HGS-OvCas). TP53 is the most frequently mutated gene in HGS-OvCas; about 50% of these tumors displayed defective homologous recombination due to germline and somatic BRCA mutations, epigenetic inactivation of BRCA and abnormalities of DNA repair genes; somatic copy number alterations are frequent in these tumors and some of them are associated with prognosis; defective NOTCH, RAS/MEK, PI3K and FOXM1 pathway signaling is frequent. Other histological subtypes were characterized by a different mutational spectrum: LGS-OvCas have increased frequency of BRAF and RAS mutations; mucinous cancers have mutation in ARID1A, PIK3CA, PTEN, CTNNB1 and RAS. Intensive research was focused to characterize ovarian cancer stem cells, based on positivity for some markers, including CD133, CD44, CD117, CD24, EpCAM, LY6A, ALDH1. Ovarian cancer cells have an intrinsic plasticity, thus explaining that in a single tumor more than one cell subpopulation, may exhibit tumor-initiating capacity. The improvements in our understanding of the molecular and cellular basis of ovarian cancers should lead to more efficacious treatments. PMID:29389895

  9. Invasive ductal carcinoma within borderline phyllodes tumor with lymph node metastases: A case report and review of the literature

    Science.gov (United States)

    WU, DI; ZHANG, HAIPENG; GUO, LIANG; YAN, XU; FAN, ZHIMIN

    2016-01-01

    Phyllodes tumor (PT) is a rare type of biphasic fibroepithelial neoplasm that may coexist with a breast tumor in rare cases. In the current study, a 52-year-old female presented with a left breast lump. Mammography and sonographic examination results suggested a diagnosis of malignant tumor. Histological analysis revealed a borderline PT with invasive ductal carcinoma (IDC) within the tumor. Due to the presence of a single micrometastasis in three of the sentinel lymph nodes, the patient underwent modified radical mastectomy. The excised tumor contained triple negative breast cancer; therefore, postoperative treatment included six cycles of chemotherapy and 25 cycles of radiotherapy. The patient exhibited no recurrence and no metastatic disease at the 23-month follow-up examination. Thus, the present study discussed the case of a female patient that presented with IDC within borderline PT and reviewed the literature on this rare type of neoplasm. Various types of breast carcinoma have been identified to coexist with PT in different masses; however, no standard therapeutic regimen has been established for the coexistence of PT and breast cancer in the same mass. The present study indicates that determination of an appropriate treatment strategy predominantly depends on the characteristics of the individual breast tumor. PMID:27073506

  10. Pancreatic neuroendocrine tumor - incidental finding during a follow-up CT for primary ovarian carcinoma

    International Nuclear Information System (INIS)

    Ivanova, D.; Balev, B.

    2013-01-01

    Pancreatic neuroendocrine tumors (PNET) are primary, usually we 11-differentiated pancreatic tumors. Their origin is not fully understood, but they are thought to develop from the pluripotent cells in the exocrine part of the pancreas. PNET are a heterogeneous group with different malignant potential. In some of the patients with sporadical forms of PNET there is association with other malignancies such as ovarian cancer, breast cancer, bladder and prostate cancers. We present a case of 50-year-old woman, with incidentally found pancreatic neoplasm, during a follow-up CT for ovarian cancer. Laparotomy and pancreatic biopsy are performed. Histological diagnosis confirms a well- differentiated endocrine tumor of the pancreas. (authors)

  11. Spectropolarimetry in the differential diagnosis of benign and malignant ovarian tumors

    Science.gov (United States)

    Peresunko, O. P.; Yermolenko, S. B.; Gruia, I.

    2018-01-01

    The aim of this study was to use the spectrophotometry method to develop a diagnostic algorithm for blood studies and the content of douglas deepening in women with ovarian tumors. A comparative analysis of the blood of healthy women and patients with ovarian cancer revealed significantly greater optical anisotropy of the latter. Qualitative studies of polarization microscopic blood images revealed a very developed microcrystalline structure. Based on the study of blood and puncture and douglas deepening of healthy women and patients with benign and malignant tumors of the ovaries, using the method of laser polarimetry, experimentally developed and clinically tested photometric and polarization criteria indicating the presence of malignancy of the tumor.

  12. HER2 expression in ovarian mucinous carcinomas in Tunisia.

    Science.gov (United States)

    Missaoui, Nabiha; Abdelkarim, Soumaya Ben; Ayachi, Malak; Hmissa, Sihem; Yaacoubi, Mohamed Taher

    2014-01-01

    Ovarian mucinous carcinoma has a poor prognosis in advanced stages and a poor response to conventional chemotherapy. An efficient treatment is not yet available. We heere investigated HER2 expression and the potential for trastuzumab therapy in ovarian mucinous tumors. Immunohistochemistry was performed in formalin-fixed, paraffin-embedded tissue from 27 ovarian mucinous tumors including 14 carcinomas and 13 borderline tumors diagnosed in the Pathology Department, Farhet Hached Hospital, Sousse, between 1993 and 2013. The HercepTest (DAKO) was used for immunohistochemistry. HER2 expression was observed in only one borderline tumor (7.7%) and in 14.3% of mucinous carcinomas of the ovary. Our results suggest that trastuzumab therapy would be an option for patients with mucinous carcinoma when the tumor has HER2 overexpression.

  13. MUC16 provides immune protection by inhibiting synapse formation between NK and ovarian tumor cells

    Directory of Open Access Journals (Sweden)

    Migneault Martine

    2010-01-01

    Full Text Available Abstract Background Cancer cells utilize a variety of mechanisms to evade immune detection and attack. Effective immune detection largely relies on the formation of an immune synapse which requires close contact between immune cells and their targets. Here, we show that MUC16, a heavily glycosylated 3-5 million Da mucin expressed on the surface of ovarian tumor cells, inhibits the formation of immune synapses between NK cells and ovarian tumor targets. Our results indicate that MUC16-mediated inhibition of immune synapse formation is an effective mechanism employed by ovarian tumors to evade immune recognition. Results Expression of low levels of MUC16 strongly correlated with an increased number of conjugates and activating immune synapses between ovarian tumor cells and primary naïve NK cells. MUC16-knockdown ovarian tumor cells were more susceptible to lysis by primary NK cells than MUC16 expressing controls. This increased lysis was not due to differences in the expression levels of the ligands for the activating receptors DNAM-1 and NKG2D. The NK cell leukemia cell line (NKL, which does not express KIRs but are positive for DNAM-1 and NKG2D, also conjugated and lysed MUC16-knockdown cells more efficiently than MUC16 expressing controls. Tumor cells that survived the NKL challenge expressed higher levels of MUC16 indicating selective lysis of MUC16low targets. The higher csMUC16 levels on the NKL resistant tumor cells correlated with more protection from lysis as compared to target cells that were never exposed to the effectors. Conclusion MUC16, a carrier of the tumor marker CA125, has previously been shown to facilitate ovarian tumor metastasis and inhibits NK cell mediated lysis of tumor targets. Our data now demonstrates that MUC16 expressing ovarian cancer cells are protected from recognition by NK cells. The immune protection provided by MUC16 may lead to selective survival of ovarian cancer cells that are more efficient in

  14. Surgical treatment of borderline and malignant phyllodes tumors: the effect of the extent of resection and tumor characteristics on patient outcome.

    Science.gov (United States)

    Onkendi, Edwin O; Jimenez, Rafael E; Spears, Grant M; Harmsen, William S; Ballman, Karla V; Hieken, Tina J

    2014-10-01

    Malignant phyllodes tumors are rare fibroepithelial breast neoplasms. Appropriate surgical management remains a subject of debate. The purpose of our study was to define optimal surgical treatment and to identify factors associated with outcome. After confirmatory pathology review, we identified 67 patients with borderline (n = 15) and malignant (n = 52) phyllodes tumors treated at our institution between 1971 and 2008. We used Cox proportional hazards models to evaluate associations between treatment, patient and tumor characteristics, and disease-free (DFS) and cancer-specific survival (CSS). Median patient age was 47 years. For 32 patients, definitive surgical treatment was wide local excision (WLE): 27 with margins ≥1 cm and 5 with margins Tumor size >5 cm, mitotic rate ≥10/10 HPF, stromal overgrowth and cellularity (all p tumors with adverse features. With long-term follow-up, extent of surgical resection did not affect DFS for patients with borderline and malignant phyllodes tumors. Tumor features, most notably stromal overgrowth, were predictive of recurrence and survival, suggesting these high-risk patients may benefit from additional therapeutic strategies.

  15. Signaling Circuits and Regulation of Immune Suppression by Ovarian Tumor-Associated Macrophages

    Directory of Open Access Journals (Sweden)

    Martin J. Cannon

    2015-05-01

    Full Text Available The barriers presented by immune suppression in the ovarian tumor microenvironment present one of the biggest challenges to development of successful tumor vaccine strategies for prevention of disease recurrence and progression following primary surgery and chemotherapy. New insights gained over the last decade have revealed multiple mechanisms of immune regulation, with ovarian tumor-associated macrophages/DC likely to fulfill a central role in creating a highly immunosuppressive milieu that supports disease progression and blocks anti-tumor immunity. This review provides an appraisal of some of the key signaling pathways that may contribute to immune suppression in ovarian cancer, with a particular focus on the potential involvement of the c-KIT/PI3K/AKT, wnt/β-catenin, IL-6/STAT3 and AhR signaling pathways in regulation of indoleamine 2,3-dioxygenase expression in tumor-associated macrophages. Knowledge of intercellular and intracellular circuits that shape immune suppression may afford insights for development of adjuvant treatments that alleviate immunosuppression in the tumor microenvironment and enhance the clinical efficacy of ovarian tumor vaccines.

  16. Circulating Microparticles in Patients with Benign and Malignant Ovarian Tumors

    NARCIS (Netherlands)

    Rank, A.; Liebhardt, S.; Zwirner, J.; Burges, A.; Nieuwland, R.; Toth, B.

    2012-01-01

    Background: Microparticles are known to be increased in various malignancies. In this prospective study, microparticle levels were evaluated in patients with benign and malignant ovarian lesions. Patients and Methods: Microparticles from platelets/megakaryocytes, activated platelets and endothelial

  17. Value of dynamic enhanced MR imaging in the differential diagnosis of benign and malignant ovarian tumors

    International Nuclear Information System (INIS)

    Shan Jun; Xu Jianmin; Gong Jingshan; Wang Xiaomei; Xu Hongli; Feng Xiaofeng

    2003-01-01

    Objective: To evaluate the value of early phase dynamic enhanced MRI in the differential diagnosis of ovarian tumors. Methods: Early phase dynamic enhanced MRI findings in 68 patients with histopathologically proved ovarian tumors were analyzed. There were 19 cases of benign tumors, 5 cases of low malignant tumors, and 44 cases of malignant tumors. The signal intensity of the solid component of tumor was measured. Peak and the slope value of enhancement were determined from time-signal intensity curve (TIC). The TIC of tumors were divided into three types according to their enhancement manner. In type I, the signal intensity increased rapidly and reached a platform soon. In type II, the signal intensity increased continuously at a slope. In type III, the signal intensity increased slowly. The TIC index of early phase, the time to peak of enhancement, and the slope value of TIC were also evaluated. Results: The TIC of the 19 benign tumors included type III in 13 cases (13/19), type II in 3 cases (3/19), and type I in 3 cases (3/19). There were 41 type I TIC (41/44) and 3 type II TIC (3/44) in the 44 case of malignant tumors. The enhancement index, the time to peak, and the slope value of the benign tumors were (68 ±27)%, (163.53±58.54) s, and (3.56±3.42) during the early phase respectively, while those of malignant ovarian tumors were(128±15)%, (72.89±10.84) s, and (9.69±1.41), respectively. The difference of the enhancement index, the time to peak, and the slope value between benign and malignant ovarian tumors was statistically significant (P<0.001). Conclusion: The benign tumors mainly showed type III enhancement curve, with low and delay enhancement, while the malignant ovarian tumors mostly showed type I enhancement curve, with high and early enhancement. The early phase dynamic enhanced MR imaging was helpful in the differential diagnosis of benign and malignant ovarian tumors

  18. Increased expression of Nlp, a potential oncogene in ovarian cancer, and its implication in carcinogenesis.

    Science.gov (United States)

    Qu, Danni; Qu, Hongyan; Fu, Ming; Zhao, Xuelian; Liu, Rong; Sui, Lihua; Zhan, Qimin

    2008-08-01

    Nlp (Ninein-like protein), a novel centrosome protein involved in microtubule nucleation, has been studied extensively in our laboratory, and its overexpression has been found in some human tumors. To understand the role of Nlp in human ovarian cancer development, we studied the correlation of Nlp expression with clinicopathological parameters and survival in epithelial ovarian cancer, and the impact of Nlp overexpression on ovarian cancer cells. Nlp expression in normal, borderline, benign and malignant epithelial ovarian tissues was examined by immunohistochemistry. The correlation between Nlp expression and tumor grade, FIGO stage and histological type was also evaluated. Survival was calculated using Kaplan-Meier estimates. Cell proliferation and apoptosis were assayed after stable transfection of pEGFP-C3-Nlp or empty vector in human ovarian cancer cell line SKOV3. Nlp was positive in 1 of 10 (10%) normal ovarian tissues, 5 of 34 (14.7%) benign tumors, 9 of 26 (34.6%) borderline tumors and 73 of 131 (56.0%) ovarian tumors. Nlp immunoreactivity intensity significantly correlated with tumor grade, but not with FIGO stage or histological type. Kaplan-Meier curves showed that Nlp overexpression was marginally associated with decreased overall survival. Overexpression of Nlp enhanced proliferation and inhibited apoptosis induced by paclitaxel in the SKOV3 cell line. Overexpression of Nlp in ovarian tumors raises the possibility that Nlp may play a role in ovarian carcinogenesis.

  19. Preoperative comparison of ultrasound and computed tomography in the diagnosis of ovarian tumors

    Energy Technology Data Exchange (ETDEWEB)

    Miyasaka, Yasuo; Watanabe, Hiromu; Hachiya, Junichi; Furuya, Yoshiro; Abe, Yutaka; Suzuki, Masahiko (Kyorin Univ., Mitaka, Tokyo (Japan). School of Medicine)

    1984-01-01

    Prospective evaluation of both ultrasound and computed tomography were performed on 543 patients with gynecologic disorders. Of the 543 patients, 143 were diagnosed as ovarian tumors by ultrasound, CT, or pathologic examination. A preoperative analysis of ovarian tumors in 143 patients is present. The sensitivity of ultrasound for malignant ovarian tumor is 83.3% (30/36), that of CT is 91.7% (33/36). The specificity of ultrasound is 80.4% (86/107), that of CT is 93.5% (100/107). Although both imaging techniques use similar diagnostic criteria, the accuracy rate of CT is slightly higher than ultrasound. Our comparative data suggest that CT increases diagnostic accuracy when ultrasound does not provide diagnostic findings.

  20. Uterine Tumor Resembling Ovarian Sex Cord Tumor (UTROSCT) Commonly Exhibits Positivity With Sex Cord Markers FOXL2 and SF-1 but Lacks FOXL2 and DICER1 Mutations.

    Science.gov (United States)

    Croce, Sabrina; de Kock, Leanne; Boshari, Talia; Hostein, Isabelle; Velasco, Valerie; Foulkes, William D; McCluggage, W Glenn

    2016-07-01

    Uterine tumor resembling ovarian sex cord tumor (UTROSCT) is a rare neoplasm which morphologically and immunohistochemically exhibits overlap with an ovarian sex cord tumor. Although many of these neoplasms are positive with markers of ovarian sex cord-stromal tumors, staining is often limited and the pathogenesis of UTROSCT is unknown. To further explore the sex cord lineage of UTROSCT, we studied 19 of these neoplasms and examined the expression of 2 recently described markers of ovarian sex cord-stromal tumors, FOXL2, and steroidogenic factor-1. We also undertook FOXL2 and DICER1 mutation analysis in these cases; a somatic missense mutation in codon C134W (402C→G) of FOXL2 gene has been demonstrated in the vast majority (>95%) of ovarian adult granulosa cell tumors and somatic DICER1 mutations are found in approximately 60% of ovarian Sertoli-Leydig cell tumors. Ten of 19 cases (53%) exhibited nuclear immunoreactivity with FOXL2 and 11 of 19 (58%) exhibited nuclear staining with steroidogenic factor-1. Neither FOXL2 nor DICER1 mutations were identified in any case where there was sufficient tumor tissue for analysis (18 and 9 cases, respectively). Despite exhibiting an immunophenotype characteristic of a sex cord-stromal tumor, mutations in FOXL2 and DICER1, the 2 most common mutations hitherto reported in ovarian sex cord-stromal tumors, are not a feature of UTROSCT.

  1. Podoplanin as Key Player of Tumor Progression and Lymph Vessel Proliferation in Ovarian Cancer.

    Science.gov (United States)

    Cobec, Ionut Marcel; Sas, Ioan; Pirtea, Laurențiu; Cimpean, Anca Maria; Moatar, Aurica Elisabeta; Ceaușu, Raluca Amalia; Raica, Marius

    2016-10-01

    Podoplanin plays a key role in tumor progression and metastasis. We evaluated lymphatics proliferation rate and podoplanin expression in tumor cells of ovarian carcinoma. Seventy-five paraffin-embedded specimens of ovarian cancer were immunohistochemically assessed in order to quantify peritumoral (LMVDP) and intratumoral (LMVDT) lymphatic microvessel density of proliferating lymphatics and for podoplanin variability in tumor cells. LMVDT correlated with proliferating tumor vessels located in the peritumoral area (p=0.024) and with the number of mature vessels located in the intratumoral area (p<0.0001), while LMVDP correlated with peritumoral mature vessels (p<0.000l). Proliferating tumor cells at the invasive front were highly positive for podoplanin. To the best of our knowledge, this study represents the first assessment of lymphatic endothelial cell proliferation correlated with podoplanin expression in tumor cells from ovarian cancer. Our data support podoplanin as a potential target that may help reduce ovarian cancer dissemination and lymphatic metastasis. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  2. Sonographic diagnosis of the contralateral ovary in patients with ovarian tumor

    International Nuclear Information System (INIS)

    Lee, Eun Ju; Jung, Jin Young; Lee, Chang Ho; Suh; Jung Ho

    1999-01-01

    To assess the usefulness of transvaginal sonography(TVS) in the detection of normal contralateral ovary and disease involvement of contralateral ovary in the patients with ovarian tumor. We compared sonographic findings with histopathologic findings of the contralateral ovary retrospectively in 87 patients, who underwent preoperative ultrasonography and laparotomy for ovarian tumor for recent 4 years. Abnormality of the contralateral ovary was confirmed in 49 (56.3%) of 87 patients. The pathologic diagnoses of contralateral ovarian lesions were bilateral involvement of the same disease in 39 patients, different tumor in four patients and non-tumorous lesion in six patients. Abnormal TVS findings of the contralateral ovary were detected in 34 of 49 patients, which shows diagnostic accuracy of 82.8%. The sensitivity and specificity were 69.4% and 100%, respectively. 15 cases which were not diagnosed by ultrasound were bilateral involvement of the same disease in 10 cases (1 serous cystadenoma, 2 cystadenocarcinoma with low malignant potential, 1 brenner tumor, 1 metastatic endometrioid cancer, 1 metastasis, 4 teratoma) and different lesions in the remaining 5 patients (2 endosalpingiosis, 1 surface inclusion cyst, 2 tuboovarian cyst). Ultrasound of the contralateral ovary in the patients with ovarian tumor shows low to a moderate degree sensitivity and accuracy. So, more intensive and targeted evaluation of contralateral ovary is needed for the more accurate diagnosis and proper treatment.

  3. Cancer Associated Fibroblasts express pro-inflammatory factors in human breast and ovarian tumors

    Energy Technology Data Exchange (ETDEWEB)

    Erez, Neta, E-mail: netaerez@post.tau.ac.il [Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel-Aviv 69978 (Israel); Glanz, Sarah [Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel-Aviv 69978 (Israel); Raz, Yael [Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel-Aviv 69978 (Israel); Department of Obstetrics and Gynecology, LIS Maternity Hospital, Tel Aviv Sourasky Medical Center, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel); Avivi, Camilla [Department of Pathology, Sheba Medical Center, Tel Hashomer, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel); Barshack, Iris [Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel-Aviv 69978 (Israel); Department of Pathology, Sheba Medical Center, Tel Hashomer, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel)

    2013-08-02

    Highlights: •CAFs in human breast and ovarian tumors express pro-inflammatory factors. •Expression of pro-inflammatory factors correlates with tumor invasiveness. •Expression of pro-inflammatory factors is associated with NF-κb activation in CAFs. -- Abstract: Inflammation has been established in recent years as a hallmark of cancer. Cancer Associated Fibroblasts (CAFs) support tumorigenesis by stimulating angiogenesis, cancer cell proliferation and invasion. We previously demonstrated that CAFs also mediate tumor-enhancing inflammation in a mouse model of skin carcinoma. Breast and ovarian carcinomas are amongst the leading causes of cancer-related mortality in women and cancer-related inflammation is linked with both these tumor types. However, the role of CAFs in mediating inflammation in these malignancies remains obscure. Here we show that CAFs in human breast and ovarian tumors express high levels of the pro-inflammatory factors IL-6, COX-2 and CXCL1, previously identified to be part of a CAF pro-inflammatory gene signature. Moreover, we show that both pro-inflammatory signaling by CAFs and leukocyte infiltration of tumors are enhanced in invasive ductal carcinoma as compared with ductal carcinoma in situ. The pro-inflammatory genes expressed by CAFs are known NF-κB targets and we show that NF-κB is up-regulated in breast and ovarian CAFs. Our data imply that CAFs mediate tumor-promoting inflammation in human breast and ovarian tumors and thus may be an attractive target for stromal-directed therapeutics.

  4. Cancer Associated Fibroblasts express pro-inflammatory factors in human breast and ovarian tumors

    International Nuclear Information System (INIS)

    Erez, Neta; Glanz, Sarah; Raz, Yael; Avivi, Camilla; Barshack, Iris

    2013-01-01

    Highlights: •CAFs in human breast and ovarian tumors express pro-inflammatory factors. •Expression of pro-inflammatory factors correlates with tumor invasiveness. •Expression of pro-inflammatory factors is associated with NF-κb activation in CAFs. -- Abstract: Inflammation has been established in recent years as a hallmark of cancer. Cancer Associated Fibroblasts (CAFs) support tumorigenesis by stimulating angiogenesis, cancer cell proliferation and invasion. We previously demonstrated that CAFs also mediate tumor-enhancing inflammation in a mouse model of skin carcinoma. Breast and ovarian carcinomas are amongst the leading causes of cancer-related mortality in women and cancer-related inflammation is linked with both these tumor types. However, the role of CAFs in mediating inflammation in these malignancies remains obscure. Here we show that CAFs in human breast and ovarian tumors express high levels of the pro-inflammatory factors IL-6, COX-2 and CXCL1, previously identified to be part of a CAF pro-inflammatory gene signature. Moreover, we show that both pro-inflammatory signaling by CAFs and leukocyte infiltration of tumors are enhanced in invasive ductal carcinoma as compared with ductal carcinoma in situ. The pro-inflammatory genes expressed by CAFs are known NF-κB targets and we show that NF-κB is up-regulated in breast and ovarian CAFs. Our data imply that CAFs mediate tumor-promoting inflammation in human breast and ovarian tumors and thus may be an attractive target for stromal-directed therapeutics

  5. FBXW7 is involved in the acquisition of the malignant phenotype in epithelial ovarian tumors

    OpenAIRE

    Kitade, Shoko; Onoyama, Ichiro; Kobayashi, Hiroaki; Yagi, Hiroshi; Yoshida, Sachiko; Kato, Masaya; Tsunematsu, Ryosuke; Asanoma, Kazuo; Sonoda, Kenzo; Wake, Norio; Hata, Kenichiro; Nakayama, Keiichi I.; Kato, Kiyoko

    2016-01-01

    FBXW7 is a ubiquitin ligase that mediates ubiquitylation of oncoproteins, such as c?Myc, cyclin E, Notch and c?Jun. FBXW7 is a known tumor?suppressor gene, and mutations in FBXW7 have been reported in various human malignancies. In this study, we examined the sequences of the FBXW7 and p53 genes in 57 ovarian cancer clinical samples. Interestingly, we found no FBXW7 mutations associated with amino acid changes. We also investigated FBXW7 expression levels in 126 epithelial ovarian tumors. FBX...

  6. YKL-40 tissue expression and plasma levels in patients with ovarian cancer

    DEFF Research Database (Denmark)

    Høgdall, Estrid V S; Ringsholt, Merete; Høgdall, Claus K

    2009-01-01

    survival. The aim of the study was to determine the expression of YKL-40 in tumor tissue and plasma in patients with borderline ovarian tumor or epithelial ovarian cancer (OC), and investigate prognostic value of this marker. METHODS: YKL-40 protein expression was determined by immunohistochemistry...... in tissue arrays from 181 borderline tumors and 473 OC. Plasma YKL-40 was determined by ELISA in preoperative samples from 19 patients with borderline tumor and 76 OC patients. RESULTS: YKL-40 protein expression was found in cancer cells, tumor associated macrophages, neutrophils and mast cells. The tumor...... stage, age and radicality after primary surgery as variables, showed that elevated plasma YKL-40 was associated with a shorter survival (HR = 2.13, 95% CI: 1.40-3.25, p = 0.0004). CONCLUSION: YKL-40 in OC tissue and plasma are related to stage and histology, but only plasma YKL-40 is a prognostic...

  7. Cisplatin Resistant Spheroids Model Clinically Relevant Survival Mechanisms in Ovarian Tumors.

    Directory of Open Access Journals (Sweden)

    Winyoo Chowanadisai

    Full Text Available The majority of ovarian tumors eventually recur in a drug resistant form. Using cisplatin sensitive and resistant cell lines assembled into 3D spheroids we profiled gene expression and identified candidate mechanisms and biological pathways associated with cisplatin resistance. OVCAR-8 human ovarian carcinoma cells were exposed to sub-lethal concentrations of cisplatin to create a matched cisplatin-resistant cell line, OVCAR-8R. Genome-wide gene expression profiling of sensitive and resistant ovarian cancer spheroids identified 3,331 significantly differentially expressed probesets coding for 3,139 distinct protein-coding genes (Fc >2, FDR < 0.05 (S2 Table. Despite significant expression changes in some transporters including MDR1, cisplatin resistance was not associated with differences in intracellular cisplatin concentration. Cisplatin resistant cells were significantly enriched for a mesenchymal gene expression signature. OVCAR-8R resistance derived gene sets were significantly more biased to patients with shorter survival. From the most differentially expressed genes, we derived a 17-gene expression signature that identifies ovarian cancer patients with shorter overall survival in three independent datasets. We propose that the use of cisplatin resistant cell lines in 3D spheroid models is a viable approach to gain insight into resistance mechanisms relevant to ovarian tumors in patients. Our data support the emerging concept that ovarian cancers can acquire drug resistance through an epithelial-to-mesenchymal transition.

  8. Expression of tumor-specific antigen MAGE, GAGE and BAGE in ovarian cancer tissues and cell lines

    Directory of Open Access Journals (Sweden)

    Yu Hao

    2010-04-01

    Full Text Available Abstract Background To observe mRNA expression of tumor-specific antigen MAGE, BAGE and GAGE in epithelial ovarian cancer tissues and cell lines, to explore the relationship between gene expression and diagnosis, treatment and prognosis of ovarian cancer, and to evaluate the feasibility of their gene products as markers, and an immunotherapy target for ovarian cancer. Methods mRNA expression of MAGE-1, MAGE-3, GAGE-1/2 and BAGE were determined by reverse transcription polymerase chain reaction (RT-PCR in 14 cases of normal ovarian tissue, 20 cases of ovarian benign tumor specimens, 41 cases of ovarian cancer specimens, and ovarian cancer cell lines SKOV3, A2780, and COC1. Results MAGE, GAGE and BAGE genes were not expressed in normal ovarian tissue. In benign tumors, only the MAGE gene was expressed; the expression rate of this gene in benign tumors was 15% (3/20. In ovarian cancer tissues, MAGE-1 and MAGE-3 was highly expressed, with expression rates of 53.7% (22/41 and 36.6% (15/41, while GAGE-1/2 and BAGE had relatively low expression, with rates of 26.8% (11/41 and 14.6% (6/41. In metastatic lesions of ovarian cancer, only MAGE-1 and BAGE were expressed, with expression rates of 28.6% (2/7 and 14.3% (1/7. The positive expression rates of MAGE-1 and MAGE-3 in serous cystadenocarcinoma were significantly higher than that in other types of ovarian cancer (P P Conclusion Tumor-specific antigen MAGE, BAGE and GAGE may play a role in the occurrence and development of ovarian cancer. These genes can be used as one of the important indicators for early diagnosis, efficacy evaluation and prognostic determination of ovarian cancer.

  9. Epigenetic modifiers upregulate MHC II and impede ovarian cancer tumor growth.

    Science.gov (United States)

    Turner, Taylor B; Meza-Perez, Selene; Londoño, Angelina; Katre, Ashwini; Peabody, Jacelyn E; Smith, Haller J; Forero, Andres; Norian, Lyse A; Straughn, J Michael; Buchsbaum, Donald J; Randall, Troy D; Arend, Rebecca C

    2017-07-04

    Expression of MHC class II pathway proteins in ovarian cancer correlates with prolonged survival. Murine and human ovarian cancer cells were treated with epigenetic modulators - histone deacetylase inhibitors and a DNA methyltransferase inhibitor. mRNA and protein expression of the MHC II pathway were evaluated by qPCR and flow cytometry. Treatment with entinostat and azacytidine of ID8 cells in vitro increased mRNA levels of Cd74, Ciita, and H2-Aa, H2-Eb1. MHC II and CD74 protein expression were increased after treatment with either agent. A dose dependent response in mRNA and protein expression was seen with entinostat. Combination treatment showed higher MHC II protein expression than with single agent treatment. In patient derived xenografts, CIITA, CD74, and MHC II mRNA transcripts were significantly increased after combination treatment. Expression of MHC II on ovarian tumors in MISIIR-Tag mice was increased with both agents relative to control. Combination treatment significantly reduced ID8 tumor growth in immune-competent mice. Epigenetic treatment increases expression of MHC II on ovarian cancer cells and impedes tumor growth. This approach warrants further study in ovarian cancer patients.

  10. Potential role of estrogen receptor beta as a tumor suppressor of epithelial ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Carine Bossard

    Full Text Available Ovarian cancer is the gynecological cancer exhibiting the highest morbidity and improvement of treatments is still required. Previous studies have shown that Estrogen-receptor beta (ERβ levels decreased along with ovarian carcinogenesis. Here, we present evidence that reintroduction of ERβ in BG-1 epithelial ovarian cancer cells, which express ERα, leads in vitro to a decrease of basal and estradiol-promoted cell proliferation. ERβ reduced the frequency of cells in S phase and increased the one of cells in G2/M phase. At the molecular level, we found that ERβ downregulated total retinoblastoma (Rb, phosphorylated Rb and phospho-AKT cellular content as well as cyclins D1 and A2. In addition, ERβ had a direct effect on ERα, by strongly inhibiting its expression and activity, which could explain part of the anti-proliferative action of ERβ. By developing a novel preclinical model of ovarian cancer based on a luminescent orthotopic xenograft in athymic Nude mice, we further revealed that ERβ expression reduces tumor growth and the presence of tumor cells in sites of metastasis, hence resulting in improved survival of mice. Altogether, these findings unveil a potential tumor-suppressor role of ERβ in ovarian carcinogenesis, which could be of potential clinical relevance for the selection of the most appropriate treatment for patients.

  11. EphA5 protein, a potential marker for distinguishing histological grade and prognosis in ovarian serous carcinoma.

    Science.gov (United States)

    Chen, Xiao; Wang, Xuan; Wei, Xue; Wang, Jiandong

    2016-11-25

    Ovarian serous carcinoma (OSC) is the most common ovarian epithelial malignancy. Disregulation of Eph/ephrin signaling has been implicated in oncogenesis and tumor progression. EphA5 receptor is one of large families of Eph tyrosine kinase receptor and is documented in the development of nervous system. Till now, there is no published data about the role of EphA5 in ovarian epithelial neoplasmas. This study aims to investigate the expression of EphA5 protein in ovarian serous carcinoma, and its relationship to clinical pathological characteristics. Sixty-one cases of ovarian serous carcinoma, 24 cases of benign ovarian serous tumors, 42 cases of serous borderline tumors and 20 cases of normal fallopian tubes were examined using immunohistochemical staining. The relationship between EphA5 expression and pathological parameters was analyzed. Kaplan-Meier survival function was used to analyze prognosis of patients. Immunostaining analysis demonstrated that the EphA5 protein was highly expressed in 100% (20/20) of normal fallopian tube samples, 100% (24/24) of benign epithelial ovarian tumors, 76% (32/42) of ovarian serous borderline tumors, and 31% (19/61) of ovarian serous carcinomas. Loss of EphA5expression was associated with tumor grade (P ovarian serous carcinoma and a potential prognostic marker.

  12. Fibroblast activation protein regulates tumor-associated fibroblasts and epithelial ovarian cancer cells.

    Science.gov (United States)

    Lai, Dongmei; Ma, Li; Wang, Fangyuan

    2012-08-01

    The fibroblast activation protein (FAP) is a cell surface serine protease which has emerged as a specific marker of tumor-associated fibroblasts (TAFs). FAP has been shown to have both in vitro dipeptidyl peptidase and collagenase activity. However, the biological function of FAP in the tumor microenvironment is largely unknown. In this study, we first show that TAFs isolated from ovarian cancer samples have the characteristics of stem cells. To explore the functional role of FAP, the protein was silenced by siRNA lentiviral vector transfection. FAP silencing inhibited the growth of TAFs in vitro, accompanied with cell cycle arrest at the G2 and S phase in TAFs. FAP silencing also reduced the stem cell marker gene expression in TAFs. SKOV3 cells do not express FAP. Although FAP-silenced SKOV3 cells induced ovarian tumors, the rate of tumor growth was significantly decreased, as shown in the xenograft mouse model. TAF phenotypes in the xenograft tumor tissues were further assayed by immunohistochemistry. The expression of TAF markers, including fibroblast-specific protein, FAP, smooth muscle actin, desmin, vascular endothelial growth factor and fibroblast growth factor was decreased in the tumor stroma induced by FAP-silenced SKOV3 cells. In conclusion, FAP is an important regulator of the microenvironment in tumor formation and targeting FAP is a potential therapeutic strategy to combat ovarian cancer.

  13. Bioprosthetic tricuspid valve replacement in carcinoid heart disease from primary ovarian carcinoid tumor.

    Science.gov (United States)

    Tsugu, Toshimitsu; Iwanaga, Shiro; Murata, Mitsushige; Fukuda, Keiichi

    2015-07-01

    Carcinoid heart disease (CHD) commonly occurs in association with primary gastrointestinal tract carcinoid tumors with hepatic metastases. Unlike primary gastrointestinal tract carcinoid tumors, primary ovarian carcinoid tumors may cause CHD without hepatic metastases, accounting for only 0.3 % of all carcinoid tumors. Only 37 cases of CHD from primary ovarian carcinoid tumors have been reported. We present a case of CHD in which tricuspid valve thickening and shortening led to reduced valve mobility with the resulting severe tricuspid regurgitation. Considering these characteristics of an abnormal tricuspid valve, we suspected CHD, but prosthetic valve replacement was performed without sufficient systemic examination before surgery. Two years after valve replacement, the patient underwent excision of a mass in the lower abdomen, which was diagnosed as an ovarian carcinoid tumor by histopathological examination. The patient has been observed for more than 3 years after tricuspid valve replacement. She has not experienced bioprosthetic valve leaflet degeneration or dysfunction, although it has been reported that bioprosthetic valves may degenerate in patients with carcinoid tumors. Sufficient systemic examinations should be performed to explore the cause of disease.

  14. The anti-tumor effect and bioactive phytochemicals of Hedyotis diffusa willd on ovarian cancer cells.

    Science.gov (United States)

    Zhang, Lin; Zhang, Jing; Qi, Bing; Jiang, Guoqiang; Liu, Jia; Zhang, Pei; Ma, Yuan; Li, Weiling

    2016-11-04

    Hedyotis diffusa willd (HDW) is a widely used medicinal herb in China. It processed various medicinal properties including antioxidative, anti-inflamatory and anti-cancer effects. This study aimed to investigate the anti-tumor effects of HDW on ovarian cancer cells and the underlying mechanisms as well as identify the bioactive compounds. Effects of HDW on the viability of ovarian cancer A2780 cells were detected by MTT assay. Apoptosis was detected by cell morphologic observation through DAPI staining and flow cytometry analysis. The migration of ovarian cancer cells which exposed to HDW were detected by wound healing and transwell assays. The protein levels of caspase 3/9, Bcl-2 and MMP-2/9 in human ovarian cancer cells treated with HDW were assessed by western blotting analysis. The potential bioactive compounds were characterized by HPLC-Q-TOF-MS. HDW significantly inhibited the growth of A2780 ovarian cancer cells and induced apoptosis. The induction of apoptosis by HDW was associated with down-regulation of anti-apoptotic protein Bcl-2 and the activation of caspase 3/9. Wound healing and transwell chamber assays indicated HDW suppressed the migration of ovarian cancer cells. HDW dramatically decreased MMP-2/9 expression. A HPLC-Q-TOF-MS analysis of HDW indicated the presence of 13 flavonoids compounds and one anthraquinone compound, which may contribute to the anticancer activity of the HDW. HDW effectively restricted the growth of ovarian cancer cells and induced apoptosis through the mitochondria-associated apoptotic pathway. Furthermore, HDW suppressed the migration of ovarian cancer cells through down-regulation of MMP-2 and MMP-9 expression. These results showed that HDW hold potential therapeutic effect for ovarian cancer patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  15. Tumor Mutation Burden Forecasts Outcome in Ovarian Cancer with BRCA1 or BRCA2 Mutations

    DEFF Research Database (Denmark)

    Birkbak, Nicolai Juul; Kochupurakkal, Bose; Gonzalez-Izarzugaza, Jose Maria

    2013-01-01

    mutations. In cancers with wild-type BRCA, tumor Nmut was associated with treatment response in patients with no residual disease after surgery. Conclusions: Tumor Nmut was associated with treatment response and with both PFS and OS in patients with highgrade serous ovarian cancer carrying BRCA1 or BRCA2......Background: Increased number of single nucleotide substitutions is seen in breast and ovarian cancer genomes carrying disease-associated mutations in BRCA1 or BRCA2. The significance of these genome-wide mutations is unknown. We hypothesize genome-wide mutation burden mirrors deficiencies in DNA...... repair and is associated with treatment outcome in ovarian cancer. Methods and Results: The total number of synonymous and non-synonymous exome mutations (Nmut), and the presence of germline or somatic mutation in BRCA1 or BRCA2 (mBRCA) were extracted from whole-exome sequences of high-grade serous...

  16. MHC class I-presented tumor antigen appraisable for T-cell responses against ovarian cancer

    Directory of Open Access Journals (Sweden)

    Jing Yao Wang

    2015-08-01

    Full Text Available The purpose of this study is to assess whether MHC class I-presented tumor antigen is appraisable for T-cell responses against ovarian cancer. In ovarian cancer cell, human leukocyte antigen A2 (HLA-A2 associated with peptides was used to promote the activation of naive T cells so as to activate antigen-specific T cells. 7 or 4 patients were observed grade 1 or 2 injection site reactions, respectively. 5, 2 or 1 patients were observed grade 1, 2 or 3 pain reactions, respectively. 4 or 1 patients were observed grade 1 or 2 induration reactions. Total number mean value of patients experiencing response to the particular peptide was 7.73, and total number mean value of peptides to which the patients responded was 7.45. MHC class I-presented tumor antigen is appraisable for T-cell responses against ovarian cancer in China.

  17. Prevention of Human Lymphoproliferative Tumor Formation in Ovarian Cancer Patient-Derived Xenografts

    Directory of Open Access Journals (Sweden)

    Kristina A. Butler

    2017-08-01

    Full Text Available Interest in preclinical drug development for ovarian cancer has stimulated development of patient-derived xenograft (PDX or tumorgraft models. However, the unintended formation of human lymphoma in severe combined immunodeficiency (SCID mice from Epstein-Barr virus (EBV–infected human lymphocytes can be problematic. In this study, we have characterized ovarian cancer PDXs which developed human lymphomas and explore methods to suppress lymphoproliferative growth. Fresh human ovarian tumors from 568 patients were transplanted intraperitoneally in SCID mice. A subset of PDX models demonstrated atypical patterns of dissemination with mediastinal masses, hepatosplenomegaly, and CD45-positive lymphoblastic atypia without ovarian tumor engraftment. Expression of human CD20 but not CD3 supported a B-cell lineage, and EBV genomes were detected in all lymphoproliferative tumors. Immunophenotyping confirmed monoclonal gene rearrangements consistent with B-cell lymphoma, and global gene expression patterns correlated well with other human lymphomas. The ability of rituximab, an anti-CD20 antibody, to suppress human lymphoproliferation from a patient's ovarian tumor in SCID mice and prevent growth of an established lymphoma led to a practice change with a goal to reduce the incidence of lymphomas. A single dose of rituximab during the primary tumor heterotransplantation process reduced the incidence of CD45-positive cells in subsequent PDX lines from 86.3% (n = 117 without rituximab to 5.6% (n = 160 with rituximab, and the lymphoma rate declined from 11.1% to 1.88%. Taken together, investigators utilizing PDX models for research should routinely monitor for lymphoproliferative tumors and consider implementing methods to suppress their growth.

  18. The role of p53 protein and MMP-2 tumor/stromal cells expression on progressive growth of ovarian neoplasms.

    Science.gov (United States)

    Grelewski, Piotr Grzegorz; Bar, Julia Krystyna

    2013-08-01

    The aim of our study was to evaluate p53 gene/protein status and MMP-2 expression in respect to ovarian tumors progress to define the role of these markers in the metastasis of ovarian carcinomas. MMP-2 and p53 alterations were evaluated on 80 malignant, 30 benign ovarian tumors, and 62 metastatic lesions by using HRM method for mutations in p53 gene and by using RT-PCR for mRNA MMP-2 level. Our data indicate that parallel expression of MMP-2 epithelial/stromal cells and p53 may enhance cells invasion and metastasis in ovarian carcinoma.

  19. A transplant recipient with a mixed germ-cell ovarian tumor

    Directory of Open Access Journals (Sweden)

    Ketata Hafed

    2008-01-01

    Full Text Available Immunosuppressed renal transplant recipients seem to be at significantly increased risk of developing neoplasms comparatively to nonimmunosuppressed individuals. A history of malignancy exposes the patient to a high risk for relapse after transplantation. We present a trans-plant recipient with a history of an ovarian mixed germ-cell tumor, with choriocarcinoma com-ponent, which was treated seven years prior to transplantation. After three years of follow-up, there was no evidence of tumor relapse. To our knowledge, there is no report of such case in the English literature. Regarding our case report and patients with a history of ovarian germ-cell neoplasm, waiting time before transplantation must take into consideration the stage of the tumor, its prognosis, the proportion of different tumor components, and the overall prognosis of the patient if transplantation is withheld.

  20. RNA quality and gene expression analysis of ovarian tumor tissue undergoing repeated thaw-freezing

    DEFF Research Database (Denmark)

    Jochumsen, Kirsten Marie; Tan, Qihua; Dahlgaard, Jesper

    2007-01-01

    undergoes repeated thawing and freezing. We evaluated the influence of repeated division of tumor samples at room temperature, on RNA quality and quantity, in addition to the gene expression profile. Sixteen ovarian tumor samples were divided in three aliquots each, undergoing respectively one, two...... unsupervised, and supervised multivariate statistical methods, reliability analysis, as well as verification using published gene lists in ovarian cancer studies. RNA quality and quantity did not change during the division procedure and microarray data showed insignificant difference in gene expression. Tumor......Gene expression profiles evaluated by microarray-based quantization of RNA are used in studies of differential diagnosis and prognosis in cancer. RNA of good quality is mandatory for this evaluation. The RNA most often comes from tumor banks with limited amount of tissue, and the tissue often...

  1. Combining multiple serum tumor markers improves detection of stage I epithelial ovarian cancer

    NARCIS (Netherlands)

    Zhang, Zhen; Yu, Yinhua; Xu, Fengji; Berchuck, Andrew; van Haaften-Day, Carolien; Havrilesky, Laura J.; de Bruijn, Henk W. A.; van der Zee, Ate G. J.; Woolas, Robert P.; Jacobs, Ian J.; Skates, Steven; Chan, Daniel W.; Bast, Robert C.

    2007-01-01

    Objective. Currently available tumor markers for ovarian cancer are still inadequate in both sensitivity and specificity to be used for population-based screening. Artificial neural network (ANN) as a modeling tool has demonstrated its ability to assimilate information from multiple sources and to

  2. Tumor infiltrating lymphocyte therapy for ovarian cancer and renal cell carcinoma

    DEFF Research Database (Denmark)

    Andersen, Rikke; Donia, Marco; Westergaard, Marie Christine Wulff

    2015-01-01

    stimulated the interest in developing this approach for other indications. Here, we summarize the early clinical data in the field of adoptive cell transfer therapy (ACT) using tumor-infiltrating lymphocytes for patients with renal cell carcinoma (RCC) and ovarian cancer (OC). In addition we describe...

  3. [An exceptional mimicker of ovarian tumors: cancer in a pelvic horseshoe kidney].

    Science.gov (United States)

    Ortiz-Mendoza, Carlos Manuel

    2013-01-01

    although the horseshoe kidney is a frequent congenital abnormality, the likelihood of it being the cause of a malignant tumor that looks like an ovarian neoplasm has not been reported. a 53-year-old female came to the hospital with a pelvic tumor. The patient had a history of a simple hysterectomy due to uterine myomatosis. At abdominal physical examination we identified a rounded hypogastric tumor, 20 cm diameter, firm, and fixed. On pelvic examination the mass was easily palpated through the vaginal fornix. The diagnosis of a probable ovarian neoplasm, caused by a residual ovary syndrome was made, therefore she was admitted to the gynecology service. Computed tomography scans showed a tumor located in the right side of a deformed pelvic kidney. Hence, the gynecology service sent the patient to the surgical oncology department, where the assumption was confirmed. The analysis of the RX studies showed a possible neoplasm from a pelvic horseshoe kidney. The patient underwent an exploratory abdominal surgery, and a 19 cm tumor was excised. The pathology department reported a chromophobe cell carcinoma. tumors in the pelvic horseshoe kidney may simulate an ovarian neoplasms in females.

  4. The clinical behavior of 124 leukemic ovarian tumors: clues for improving the poor prognosis.

    Science.gov (United States)

    Cunningham, Isabel

    2013-07-01

    The clinical behavior of acute leukemic tumors at each organ site must be recognized if relapse is to be prevented. The courses of 124 cases of leukemic ovarian tumors were analyzed with survival durations obtained from authors. Local expansive growth and invasion of contiguous organs similar to epithelial ovarian cancer was seen in both acute myeloid (AML) and lymphoid (ALL) leukemias. Overall, 56% survived 1 year. Tumors at other sites were clinically apparent on presentation in over half the cases without simultaneous marrow relapse, and next relapse was as common in extramedullary sites as in marrow. Leukemic ovarian tumors were generally resistant to chemotherapy, and lengthy survivals were seen most often after complete excision together with systemic therapy. This study documents similar behavior in AML and ALL tumors and that they are rarely isolated to a single ovary. It suggests that scanning could improve our ability to find and eradicate occult tumors which, because of chemoresistance, prevent the cure of leukemia for most patients who develop them.

  5. Recognition of serous ovarian tumors in human samples by multimodal nonlinear optical microscopy.

    Science.gov (United States)

    Adur, Javier; Pelegati, Vitor B; Costa, Leverson F L; Pietro, Luciana; de Thomaz, Andre A; Almeida, Diogo B; Bottcher-Luiz, Fatima; Andrade, Liliana A L A; Cesar, Carlos L

    2011-09-01

    We used a multimodal nonlinear optics microscopy, specifically two-photon excited fluorescence (TPEF), second and third harmonic generation (SHG∕THG) microscopies, to observe pathological conditions of ovarian tissues obtained from human samples. We show that strong TPEF + SHG + THG signals can be obtained in fixed samples stained with hematoxylin and eosin (H&E) stored for a very long time, and that H&E staining enhanced the THG signal. We then used the multimodal TPEF-SHG-THG microscopies in a stored file of H&E stained samples of human ovarian cancer to obtain complementary information about the epithelium∕stromal interface, such as the transformation of epithelium surface (THG) and the overall fibrillary tissue architecture (SHG). This multicontrast nonlinear optics microscopy is able to not only differentiate between cancerous and healthy tissue, but can also distinguish between normal, benign, borderline, and malignant specimens according to their collagen disposition and compression levels within the extracellular matrix. The dimensions of the layers of epithelia can also be measured precisely and automatically. Our data demonstrate that optical techniques can detect pathological changes associated with ovarian cancer.

  6. Recognition of serous ovarian tumors in human samples by multimodal nonlinear optical microscopy

    Science.gov (United States)

    Adur, Javier; Pelegati, Vitor B.; Costa, Leverson F. L.; Pietro, Luciana; de Thomaz, Andre A.; Almeida, Diogo B.; Bottcher-Luiz, Fatima; Andrade, Liliana A. L. A.; Cesar, Carlos L.

    2011-09-01

    We used a multimodal nonlinear optics microscopy, specifically two-photon excited fluorescence (TPEF), second and third harmonic generation (SHG/THG) microscopies, to observe pathological conditions of ovarian tissues obtained from human samples. We show that strong TPEF + SHG + THG signals can be obtained in fixed samples stained with hematoxylin and eosin (H&E) stored for a very long time, and that H&E staining enhanced the THG signal. We then used the multimodal TPEF-SHG-THG microscopies in a stored file of H&E stained samples of human ovarian cancer to obtain complementary information about the epithelium/stromal interface, such as the transformation of epithelium surface (THG) and the overall fibrillary tissue architecture (SHG). This multicontrast nonlinear optics microscopy is able to not only differentiate between cancerous and healthy tissue, but can also distinguish between normal, benign, borderline, and malignant specimens according to their collagen disposition and compression levels within the extracellular matrix. The dimensions of the layers of epithelia can also be measured precisely and automatically. Our data demonstrate that optical techniques can detect pathological changes associated with ovarian cancer.

  7. Tumor necrosis factor-alpha and its receptors in epithelial ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Jacek Nikliński

    2010-05-01

    Full Text Available The aim of the present study was to characterize the expression pattern of tumor necrosis factor (TNF-alpha and its receptors (TNF-Rs in the epithelial ovarian cancer (EOC and compare these results with the outcome of 126 patients. Presence of TNF-alpha, TNFR-1 and TNFR-2 were studied by Western blotting and immunohistochemistry. The proportion of samples positive for TNF-alpha and TNF-R2 was higher in epithelial ovarian cancer patients than in benign ovarian diseases (p<0.001 and p=0.016, respectively. Immunostaining intensity of TNF-R2 were correlated with tumor stage (p<0.001 and with reduced mean survival time (MST (p=0.002. The results of the present study suggested that tissue expression of TNF-R2 in epithelial ovarian cancer was correlated with the highest risk of cancer progression. Thus, the clinical value of activated TNF system in epithelial ovarian cancer needs to be further investigated.

  8. Ovarian tumor attachment, invasion and vascularization reflect unique microenvironments in the peritoneum:Insights from xenograft and mathematical models

    Directory of Open Access Journals (Sweden)

    Mara P. Steinkamp

    2013-05-01

    Full Text Available Ovarian cancer relapse is often characterized by metastatic spread throughout the peritoneal cavity with tumors attached to multiple organs. In this study, interaction of ovarian tumor cells with the peritoneal tumor microenvironment was evaluated in a xenograft model based on intraperitoneal injection of fluorescent SKOV3.ip1 ovarian cancer cells. Intra-vital microscopy of mixed GFP-RFP cell populations injected into the peritoneum demonstrated that tumor cells aggregate and attach as mixed spheroids, emphasizing the importance of homotypic adhesion in tumor formation. Electron microscopy provided high resolution structural information about local attachment sites. Experimental measurements from the mouse model were used to build a three-dimensional cellular Potts ovarian tumor model (OvTM that examines ovarian tumor cell attachment, chemotaxis, growth and vascularization. OvTM simulations provide insight into the relative influence of tumor cell-cell adhesion, oxygen availability, and local architecture on tumor growth and morphology. Notably, tumors on the mesentery, omentum or spleen readily invade the open architecture, while tumors attached to the gut encounter barriers that restrict invasion and instead rapidly expand into the peritoneal space. Simulations suggest that rapid neovascularization of SKOV3.ip1 tumors is triggered by constitutive release of angiogenic factors in the absence of hypoxia. This research highlights the importance of cellular adhesion and tumor microenvironment in the seeding of secondary ovarian tumors on diverse organs within the peritoneal cavity. Results of the OvTM simulations indicate that invasion is strongly influenced by features underlying the mesothelial lining at different sites, but is also affected by local production of chemotactic factors. The integrated in vivo mouse model and computer simulations provide a unique platform for evaluating targeted therapies for ovarian cancer relapse.

  9. Role of Receptor Sialylation in the Ovarian Tumor Cell Phenotype

    Science.gov (United States)

    2014-08-01

    biomarker for ovarian cancer progression, and new molecular target for therapeutic intervention . The identification of new mechanistic pathways...overexpressed in cervical (30), testicular (31), and pancreatic (32) cancers , and ST6Gal-I levels are higher in metastatic versus primary pros- tate cancer (34...C, Ansorge W, et al. Embryonic stem cell-like features of testicular carcinoma in situ revealed by genome-wide gene expression profiling. Cancer Res

  10. Nedd4L expression is decreased in ovarian epithelial cancer tissues compared to ovarian non-cancer tissue.

    Science.gov (United States)

    Yang, Qiuyun; Zhao, Jinghe; Cui, Manhua; Gi, Shuting; Wang, Wei; Han, Xiaole

    2015-12-01

    Recent studies have demonstrated that the neural precursor cell expressed, developmentally downregulated 4-like (Nedd4L) gene plays a role in the progression of various cancers. However, reports describing Nedd4L expression in ovarian cancer tissues are limited. A cohort (n = 117) of archival formalin-fixed, paraffin embedded resected normal ovarian epithelial tissues (n = 10), benign ovarian epithelial tumor tissues (n = 10), serous borderline ovarian epithelial tumor tissues (n = 14), mucous borderline ovarian epithelial tumor tissues (n = 11), and invasive ovarian epithelial cancer tissues (n = 72) were assessed for Nedd4L protein expression using immunohistochemistry. Nedd4L protein expression was significantly decreased in invasive ovarian epithelial cancer tissues compared to non-cancer tissues (P < 0.05). Decreased Nedd4L protein expression correlated with clinical stage, pathological grade, lymph node metastasis and survival (P < 0.05). Nedd4L protein expression may be an independent prognostic marker of ovarian cancer development. © 2015 Japan Society of Obstetrics and Gynecology.

  11. Networking for ovarian rare tumors: a significant breakthrough improving disease management.

    Science.gov (United States)

    Chiannilkulchai, N; Pautier, P; Genestie, C; Bats, A S; Vacher-Lavenu, M C; Devouassoux-Shisheboran, M; Treilleux, I; Floquet, A; Croce, S; Ferron, G; Mery, E; Pomel, C; Penault-Llorca, F; Lefeuvre-Plesse, C; Henno, S; Leblanc, E; Lemaire, A S; Averous, G; Kurtz, J E; Ray-Coquard, I

    2017-06-01

    Rare ovarian tumors represent >20% of all ovarian cancers. Given the rarity of these tumors, natural history, prognostic factors are not clearly identified. The extreme variability of patients (age, histological subtypes, stage) induces multiple and complex therapeutic strategies. Since 2011, a national network with a dedicated system for referral, up to 22 regional and three national reference centers (RC) has been supported by the French National Cancer Institute (INCa). The network aims to prospectively monitor the management of rare ovarian tumors and provide an equal access to medical expertise and innovative treatments to all French patients through a dedicated website, www.ovaire-rare.org. Over a 5-year activity, 4612 patients have been included. Patients' inclusions increased from 553 in 2011 to 1202 in 2015. Expert pathology review and patients' files discussion in dedicated multidisciplinary tumor boards increased from 166 cases in 2011 (25%) to 538 (45%) in 2015. Pathology review consistently modified the medical strategy in 5-9% every year. The rate of patients' files discussed in RC similarly increased from 294 (53%) to 789 (66%). An increasing number (357 in 5 years) of gynecologic (non-ovarian) rare tumors were also registered by physicians seeking for pathological or medical advice from expert tumor boards. Such a nation-wide organization for rare gynecological tumors has invaluable benefits, not only for patients, but also for epidemiological, clinical and biological research. © The Author 2017. 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.

  12. Expression of tumor-specific antigen MAGE, GAGE and BAGE in ovarian cancer tissues and cell lines

    International Nuclear Information System (INIS)

    Zhang, Shiqian; Zhou, Xiaoliang; Yu, Hao; Yu, Yunhai

    2010-01-01

    To observe mRNA expression of tumor-specific antigen MAGE, BAGE and GAGE in epithelial ovarian cancer tissues and cell lines, to explore the relationship between gene expression and diagnosis, treatment and prognosis of ovarian cancer, and to evaluate the feasibility of their gene products as markers, and an immunotherapy target for ovarian cancer. mRNA expression of MAGE-1, MAGE-3, GAGE-1/2 and BAGE were determined by reverse transcription polymerase chain reaction (RT-PCR) in 14 cases of normal ovarian tissue, 20 cases of ovarian benign tumor specimens, 41 cases of ovarian cancer specimens, and ovarian cancer cell lines SKOV3, A2780, and COC1. MAGE, GAGE and BAGE genes were not expressed in normal ovarian tissue. In benign tumors, only the MAGE gene was expressed; the expression rate of this gene in benign tumors was 15% (3/20). In ovarian cancer tissues, MAGE-1 and MAGE-3 was highly expressed, with expression rates of 53.7% (22/41) and 36.6% (15/41), while GAGE-1/2 and BAGE had relatively low expression, with rates of 26.8% (11/41) and 14.6% (6/41). In metastatic lesions of ovarian cancer, only MAGE-1 and BAGE were expressed, with expression rates of 28.6% (2/7) and 14.3% (1/7). The positive expression rates of MAGE-1 and MAGE-3 in serous cystadenocarcinoma were significantly higher than that in other types of ovarian cancer (P < 0.05). Gene expression rate was not correlated with menopause or lymph node metastasis. Positive expression of MAGE-1 and MAGE-3 was positively correlated with tumor differentiation and the clinical stage of the ovarian cancer. In addition, the positive expression rate of BAGE was significantly higher in ovarian cancer patients with ascites (P < 0.05). The mRNA expression profiles of MAGE, GAGE and BAGE in ovarian carcinoma cell lines SKOV3, A2780 and COC1 varied, but there was at least one gene expressed in each cell line. Tumor-specific antigen MAGE, BAGE and GAGE may play a role in the occurrence and development of ovarian cancer

  13. Gene expression analysis of matched ovarian primary tumors and peritoneal metastasis

    Directory of Open Access Journals (Sweden)

    Malek Joel A

    2012-06-01

    Full Text Available Abstract Background Ovarian cancer is the most deadly gynecological cancer due to late diagnosis at advanced stage with major peritoneal involvement. To date most research has focused on primary tumor. However the prognosis is directly related to residual disease at the end of the treatment. Therefore it is mandatory to focus and study the biology of meatastatic disease that is most frequently localized to the peritoneal caivty in ovarian cancer. Methods We used high-density gene expression arrays to investigate gene expression changes between matched primary and metastatic (peritoneal lesions. Results Here we show that gene expression profiles in peritoneal metastasis are significantly different than their matched primary tumor and these changes are affected by underlying copy number variation differences among other causes. We show that differentially expressed genes are enriched in specific pathways including JAK/STAT pathway, cytokine signaling and other immune related pathways. We show that underlying copy number variations significantly affect gene expression. Indeed patients with important differences in copy number variation displayed greater gene expression differences between their primary and matched metastatic lesions. Conclusions Our analysis shows a very specific targeting at both the genomic and transcriptomic level to upregulate certain pathways in the peritoneal metastasis of ovarian cancer. Moreover, while primary tumors use certain pathways we identify distinct differences with metastatic lesions. The variation between primary and metastatic lesions should be considered in personalized treatment of ovarian cancer.

  14. Control of Tumor Initiation by NKG2D Naturally Expressed on Ovarian Cancer Cells

    Directory of Open Access Journals (Sweden)

    Xin Cai

    2017-06-01

    Full Text Available Cancer cells may co-opt the NKG2D lymphocyte receptor to complement the presence of its ligands for autonomous stimulation of oncogenic signaling. Previous studies raise the possibility that cancer cell NKG2D may induce high malignancy traits, but its full oncogenic impact is unknown. Using epithelial ovarian cancer as model setting, we show here that ex vivo NKG2D+ cancer cells have stem-like capacities, and provide formal in vivo evidence linking NKG2D stimulation with the development and maintenance of these functional states. NKG2D+ ovarian cancer cell populations harbor substantially greater capacities for self-renewing in vitro sphere formation and in vivo tumor initiation in immunodeficient (NOD scid gamma mice than NKG2D− controls. Sphere formation and tumor initiation are impaired by NKG2D silencing or ligand blockade using antibodies or a newly designed pan ligand-masking NKG2D multimer. In further support of pathophysiological significance, a prospective study of 47 high-grade serous ovarian cancer cases revealed that the odds of disease recurrence were significantly greater and median progression-free survival rates higher among patients with above and below median NKG2D+ cancer cell frequencies, respectively. Collectively, our results define cancer cell NKG2D as an important regulator of tumor initiation in ovarian cancer and presumably other malignancies and thus challenge current efforts in immunotherapy aimed at enhancing NKG2D function.

  15. Symptomatic ovarian steroid cell tumor not otherwise specified in a post-menopausal woman

    Directory of Open Access Journals (Sweden)

    Neha Sood

    2016-06-01

    Full Text Available Steroid cell tumor not otherwise specified (NOS is a rare subtype of sex cord stromal tumor of the ovary and contributes less than 0.1% of all ovarian neoplasms. The majority of tumors occur in pre-menopausal women (mean age: 43 years, in which 56-77% of patients present with virilization due to excess testosterone. An 80-year-old woman with worsening alopecia and excessive growth of coarse hair on abdomen and genital area was found to have elevated serum testosterone level (462 ng/mL. Radiologic studies were consistent with bilateral adrenal adenomas. Bilateral adrenal venous sampling ruled out the adrenal gland as origin of hormone secretion. A diagnostic and therapeutic bilateral salpingooophorectomy confirmed steroid cell tumor NOS of the left ovary. Post-operatively, the patient had complete resolution of her symptoms and normalization of testosterone level. Our case emphasizes the importance of a clinical suspicion for an occult testosterone secreting ovarian tumor in a symptomatic patient without obvious ovarian mass on imaging.

  16. Serum angiopoietin-2 and soluble VEGFR-2 levels predict malignancy of ovarian neoplasm and poor prognosis in epithelial ovarian cancer.

    Science.gov (United States)

    Sallinen, Hanna; Heikura, Tommi; Koponen, Jonna; Kosma, Veli-Matti; Heinonen, Seppo; Ylä-Herttuala, Seppo; Anttila, Maarit

    2014-09-23

    The aim of the study was to explore the serum levels of eight angiogenesis biomarkers in patients with benign, borderline or malignant epithelial ovarian neoplasms and to compare them to those of healthy controls. In addition, we aimed to study how those biomarkers predict the clinical course and survival of patients with epithelial ovarian cancer. We enrolled 132 patients with ovarian neoplasms and 32 unaffected women in this study. Serum samples were collected preoperatively at the time of diagnosis and the levels of angiogenesis biomarkers were measured with an ELISA. Levels of Ang-1, Ang-2, VEGF, VEGF-D, VEGF/sVEGFR-2 and Ang-2/ sVEGFR-2 ratios were elevated whereas sVEGFR-2 was lower in patients with ovarian carcinoma than in women with normal ovaries, benign and/or borderline ovarian neoplasms. In ROC analysis, the area under the curve for serum Ang-2/sVEGFR-2 ratio (0.76) was greater than Ang-2 (0.75) and VEGF (0.65) but lower than for CA 125 (0.90) to differentiate ovarian cancer from benign or borderline ovarian tumors. In ovarian cancer high Ang-2/sVEGFR-2 ratio was associated with the presence of ascites, high stage and grade of ovarian cancer, with the size of primary residual tumor>1 cm and with recurrence of disease. Elevated Ang-2, VEGF, VEGF/sVEGFR-2, Ang-2/VEGF and Ang-2/sVEGFR-2 ratios and low level of sVEGFR-2 were significant predictors of poor overall survival (OS) and recurrence free survival (RFS) in univariate survival analyses. Ovarian cancer patients had elevated levels of angiogenesis related growth factors in circulation reflecting increased angiogenesis and poor prognosis. The serum level of Ang-2 predicted most accurately poor OS and Ang-2/sVEGFR-2 ratio malignancy of ovarian neoplasms and short RFS.

  17. Expression profiling of primary and metastatic ovarian tumors reveals differences indicative of aggressive disease.

    Directory of Open Access Journals (Sweden)

    Alexander S Brodsky

    Full Text Available The behavior and genetics of serous epithelial ovarian cancer (EOC metastasis, the form of the disease lethal to patients, is poorly understood. The unique properties of metastases are critical to understand to improve treatments of the disease that remains in patients after debulking surgery. We sought to identify the genetic and phenotypic landscape of metastatic progression of EOC to understand how metastases compare to primary tumors. DNA copy number and mRNA expression differences between matched primary human tumors and omental metastases, collected at the same time during debulking surgery before chemotherapy, were measured using microarrays. qPCR and immunohistochemistry validated findings. Pathway analysis of mRNA expression revealed metastatic cancer cells are more proliferative and less apoptotic than primary tumors, perhaps explaining the aggressive nature of these lesions. Most cases had copy number aberrations (CNAs that differed between primary and metastatic tumors, but we did not detect CNAs that are recurrent across cases. A six gene expression signature distinguishes primary from metastatic tumors and predicts overall survival in independent datasets. The genetic differences between primary and metastatic tumors, yet common expression changes, suggest that the major clone in metastases is not the same as in primary tumors, but the cancer cells adapt to the omentum similarly. Together, these data highlight how ovarian tumors develop into a distinct, more aggressive metastatic state that should be considered for therapy development.

  18. Inhibin as a tumor marker of ovarian cancer in postmenopausal women

    Directory of Open Access Journals (Sweden)

    Modarres Gilani M

    2010-05-01

    Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Inhibin is a dimeric glycoprotein that has a depressive effect on the anterior hypophys secretion. The level of this tumor marker is undetectable in menopause women. In patients with gynecological cancer, especially granulosa and epidermal-type (mucinous, ovarian cancers considerable increase in the serum level of inhibin has been reported. The increased level of inhibin has been reported in patients with recurrent ovarian cancer."n"nMethods: We measured total serum inhibin and CA125 tumor marker level in 38 postmenopausal women with pathologically confirmed ovarian cancer before and after surgery out of 51 suspected women. Our control group were postmenopausal women that attended to our clinic for routine gynecologic check up. Both tumor markers were measured in these patients too."n"nResults: Among 38 women with ovarian cancer, 13(34.2% had elevated serum levels of total inhibin. Among the 16 women with serous adenocarcinoma, 3 patients (18.8% had elevated serum levels of inhibin. All the three women with granulosa cell tumor had elevated serum levels of inhibin (100% and 3 of 4(75% women with mucinous ovarian cancer had the same result. three out of 38 women in control group had elevated serum levels of

  19. Inflammatory Cytokine Tumor Necrosis Factor α Confers Precancerous Phenotype in an Organoid Model of Normal Human Ovarian Surface Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Joseph Kwong

    2009-06-01

    Full Text Available In this study, we established an in vitro organoid model of normal human ovarian surface epithelial (HOSE cells. The spheroids of these normal HOSE cells resembled epithelial inclusion cysts in human ovarian cortex, which are the cells of origin of ovarian epithelial tumor. Because there are strong correlations between chronic inflammation and the incidence of ovarian cancer, we used the organoid model to test whether protumor inflammatory cytokine tumor necrosis factor α would induce malignant phenotype in normal HOSE cells. Prolonged treatment of tumor necrosis factor α induced phenotypic changes of the HOSE spheroids, which exhibited the characteristics of precancerous lesions of ovarian epithelial tumors, including reinitiation of cell proliferation, structural disorganization, epithelial stratification, loss of epithelial polarity, degradation of basement membrane, cell invasion, and overexpression of ovarian cancer markers. The result of this study provides not only an evidence supporting the link between chronic inflammation and ovarian cancer formation but also a relevant and novel in vitro model for studying of early events of ovarian cancer.

  20. Serum and cystic fluid levels of soluble interleukin-2 receptor-alpha in patients with epithelial ovarian tumors are correlated

    NARCIS (Netherlands)

    de Bruijn, HWA; ten Hoor, KA; van der Zee, AGJ

    1998-01-01

    At the diagnosis of ovarian cancer, patients have higher serum levels of soluble interleukin-2 receptor-alpha (IL2R alpha) compared to patients with benign ovarian tumors or healthy blood donors (means of 750 vs. 469 and 390 U/ml, respectively, p <0.001), Serum levels were positively related to the

  1. Tumor mutation burden forecasts outcome in ovarian cancer with BRCA1 or BRCA2 mutations.

    Science.gov (United States)

    Birkbak, Nicolai Juul; Kochupurakkal, Bose; Izarzugaza, Jose M G; Eklund, Aron C; Li, Yang; Liu, Joyce; Szallasi, Zoltan; Matulonis, Ursula A; Richardson, Andrea L; Iglehart, J Dirk; Wang, Zhigang C

    2013-01-01

    Increased number of single nucleotide substitutions is seen in breast and ovarian cancer genomes carrying disease-associated mutations in BRCA1 or BRCA2. The significance of these genome-wide mutations is unknown. We hypothesize genome-wide mutation burden mirrors deficiencies in DNA repair and is associated with treatment outcome in ovarian cancer. The total number of synonymous and non-synonymous exome mutations (Nmut), and the presence of germline or somatic mutation in BRCA1 or BRCA2 (mBRCA) were extracted from whole-exome sequences of high-grade serous ovarian cancers from The Cancer Genome Atlas (TCGA). Cox regression and Kaplan-Meier methods were used to correlate Nmut with chemotherapy response and outcome. Higher Nmut correlated with a better response to chemotherapy after surgery. In patients with mBRCA-associated cancer, low Nmut was associated with shorter progression-free survival (PFS) and overall survival (OS), independent of other prognostic factors in multivariate analysis. Patients with mBRCA-associated cancers and a high Nmut had remarkably favorable PFS and OS. The association with survival was similar in cancers with either BRCA1 or BRCA2 mutations. In cancers with wild-type BRCA, tumor Nmut was associated with treatment response in patients with no residual disease after surgery. Tumor Nmut was associated with treatment response and with both PFS and OS in patients with high-grade serous ovarian cancer carrying BRCA1 or BRCA2 mutations. In the TCGA cohort, low Nmut predicted resistance to chemotherapy, and for shorter PFS and OS, while high Nmut forecasts a remarkably favorable outcome in mBRCA-associated ovarian cancer. Our observations suggest that the total mutation burden coupled with BRCA1 or BRCA2 mutations in ovarian cancer is a genomic marker of prognosis and predictor of treatment response. This marker may reflect the degree of deficiency in BRCA-mediated pathways, or the extent of compensation for the deficiency by alternative

  2. Distinct Patterns of Stromal and Tumor Expression of ROR1 and ROR2 in Histological Subtypes of Epithelial Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    C.E. Henry

    2017-06-01

    Full Text Available OBJECTIVE: The ROR1 and ROR2 receptor tyrosine kinases have both been implicated in ovarian cancer progression and have been shown to drive migration and invasion. There is an increasing importance of the role of stroma in ovarian cancer metastasis; however, neither ROR1 nor ROR2 expression in tumor or stromal cells has been analyzed in the same clinical cohort. AIM: To determine ROR1 and ROR2 expression in ovarian cancer and surrounding microenvironment and examine associations with clinicopathological characteristics. METHODS: Immunohistochemistry for ROR1 and ROR2 was used to assess receptor expression in a cohort of epithelial ovarian cancer patients (n = 178. Results were analyzed in relation to clinical and histopathological characteristics and survival. Matched patient sample case studies of normal, primary, and metastatic lesions were used to examine ROR expression in relation to ovarian cancer progression. RESULTS: ROR1 and ROR2 are abnormally expressed in malignant ovarian epithelium and stroma. Higher ROR2 tumor expression was found in early-stage, low-grade endometrioid carcinomas. ROR2 stromal expression was highest in the serous subtype. In matched patient case studies, metastatic samples had higher expression of ROR2 in the stroma, and a recurrent sample had the highest expression of ROR2 in both tumor and stroma. CONCLUSION: ROR1 and ROR2 are expressed in tumor-associated stroma in all histological subtypes of ovarian cancer and hold potential as therapeutic targets which may disrupt tumor and stroma interactions.

  3. Central precocious puberty and granulosa cell ovarian tumor in an 8-year old female

    Directory of Open Access Journals (Sweden)

    Valeria Calcaterra

    2013-07-01

    Full Text Available Ovarian tumors associated with hormonal changes of the peripheral iso-sexual precocious puberty are of common presentation. We describe here a rare case of juvenile granulosa cell tumor in a female with central precocious puberty (CPP. An 8-year old girl with CPP presented with vaginal bleeding four months after the diagnosis and before starting treatment with gonadotropin-releasing hormone (GnRH-analogs. Suppression of basal follicle-stimulating hormone (FSH level, elevation of serum estradiol, progesterone and Cancer Antigen-125 were documented. Abdominal ultrasound examination (US and magnetic resonance imaging showed a pelvic mass affecting the left ovary. A left salpingo-oophorectomy was performed and the mass was totally resected. Juvenile granulosa cell ovarian tumor was diagnosed. One month post surgery, estradiol and progesterone decreased to values of the first evaluation and FSH increased; Cancer Antigen-125 resulted normal while ultrasound pelvic examination showed absence of pelvic masses. In our patient, the tumor had grown very quickly since hormonal data demonstrated a CPP without any evidence of ovarian mass on US only four months before diagnosis. The overstimulation of the FSH or aberrant activation of FSH receptors may have contributed to the development of the mass.

  4. Unique proteome signature of post-chemotherapy ovarian cancer ascites-derived tumor cells

    Science.gov (United States)

    Ahmed, Nuzhat; Greening, David; Samardzija, Chantel; Escalona, Ruth M.; Chen, Maoshan; Findlay, Jock K.; Kannourakis, George

    2016-01-01

    Eighty % of ovarian cancer patients diagnosed at an advanced-stage have complete remission after initial surgery and chemotherapy. However, most patients die within <5 years due to episodes of recurrences resulting from the growth of residual chemoresistant cells. In an effort to identify mechanisms associated with chemoresistance and recurrence, we compared the expression of proteins in ascites-derived tumor cells isolated from advanced-stage ovarian cancer patients obtained at diagnosis (chemonaive, CN) and after chemotherapy treatments (chemoresistant/at recurrence, CR) by using in-depth, high-resolution label-free quantitative proteomic profiling. A total of 2,999 proteins were identified. Using a stringent selection criterion to define only significantly differentially expressed proteins, we report identification of 353 proteins. There were significant differences in proteins encoding for immune surveillance, DNA repair mechanisms, cytoskeleton rearrangement, cell-cell adhesion, cell cycle pathways, cellular transport, and proteins involved with glycine/proline/arginine synthesis in tumor cells isolated from CR relative to CN patients. Pathway analyses revealed enrichment of metabolic pathways, DNA repair mechanisms and energy metabolism pathways in CR tumor cells. In conclusion, this is the first proteomics study to comprehensively analyze ascites-derived tumor cells from CN and CR ovarian cancer patients. PMID:27470985

  5. Sulforaphane reduces molecular response to hypoxia in ovarian tumor cells independently of their resistance to chemotherapy.

    Science.gov (United States)

    Pastorek, Michal; Simko, Veronika; Takacova, Martina; Barathova, Monika; Bartosova, Maria; Hunakova, Luba; Sedlakova, Olga; Hudecova, Sona; Krizanova, Olga; Dequiedt, Franck; Pastorekova, Silvia; Sedlak, Jan

    2015-07-01

    One of the recently emerging anticancer strategies is the use of natural dietary compounds, such as sulforaphane, a cancer-chemopreventive isothiocyanate found in broccoli. Based on the growing evidence, sulforaphane acts through molecular mechanisms that interfere with multiple oncogenic pathways in diverse tumor cell types. Herein, we investigated the anticancer effects of bioavailable concentrations of sulforaphane in ovarian carcinoma cell line A2780 and its two derivatives, adriamycin-resistant A2780/ADR and cisplatin-resistant A2780/CP cell lines. Since tumor microenvironment is characterized by reduced oxygenation that induces aggressive tumor phenotype (such as increased invasiveness and resistance to chemotherapy), we evaluated the effects of sulforaphane in ovarian cancer cells exposed to hypoxia (2% O2). Using the cell-based reporter assay, we identified several oncogenic pathways modulated by sulforaphane in hypoxia by activating anticancer responses (p53, ARE, IRF-1, Pax-6 and XRE) and suppressing responses supporting tumor progression (AP-1 and HIF-1). We further showed that sulforaphane decreases the level of HIF-1α protein without affecting its transcription and stability. It can also diminish transcription and protein level of the HIF-1 target, CA IX, which protects tumor cells from hypoxia-induced pH imbalance and facilitates their migration/invasion. Accordingly, sulforaphane treatment leads to diminished pH regulation and reduced migration of ovarian carcinoma cells. These effects occur in all three ovarian cell lines suggesting that sulforaphane can overcome the chemoresistance of cancer cells. This offers a path potentially exploitable in sensitizing resistant cancer cells to therapy, and opens a window for the combined treatments of sulforaphane either with conventional chemotherapy, natural compounds, or with other small molecules.

  6. Modulators of Response to Tumor Necrosis-Related Apoptosis-Inducing Ligand (TRAIL) Therapy in Ovarian Cancer

    National Research Council Canada - National Science Library

    Behbakht, Kian

    2008-01-01

    .... More effective therapies are urgently needed. One of the most promising therapies in development for ovarian cancer is the use of either the Tumor Necrosis Factor-related Apoptosis Inducing Ligand (TRAIL...

  7. HORMONAL CONTROL OF OVARIAN FUNCTION FOLLOWING CHLOROTRIAZINE EXPOSURE: EFFECT ON REPRODUCTIVE FUNCTION AND MAMMARY GLAND TUMOR DEVELOPMENT

    Science.gov (United States)

    Hormonal Control of Ovarian Function Following Chlorotriazine Exposure: Effect on Reproductive Function and Mammary Gland Tumor Development. Ralph L. Cooper, Susan C. Laws, Michael G. Narotsky, Jerome M. Goldman, and Tammy E. StokerAbstractThe studies review...

  8. Gemcitabine Hydrochloride With or Without WEE1 Inhibitor MK-1775 in Treating Patients With Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

    Science.gov (United States)

    2017-11-06

    Ovarian Brenner Tumor; Ovarian Carcinosarcoma; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Serous Surface Papillary Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Undifferentiated Ovarian Carcinoma

  9. Expression of tumor-specific antigen MAGE, GAGE and BAGE in ovarian cancer tissues and cell lines.

    Science.gov (United States)

    Zhang, Shiqian; Zhou, Xiaoliang; Yu, Hao; Yu, Yunhai

    2010-04-27

    To observe mRNA expression of tumor-specific antigen MAGE, BAGE and GAGE in epithelial ovarian cancer tissues and cell lines, to explore the relationship between gene expression and diagnosis, treatment and prognosis of ovarian cancer, and to evaluate the feasibility of their gene products as markers, and an immunotherapy target for ovarian cancer. mRNA expression of MAGE-1, MAGE-3, GAGE-1/2 and BAGE were determined by reverse transcription polymerase chain reaction (RT-PCR) in 14 cases of normal ovarian tissue, 20 cases of ovarian benign tumor specimens, 41 cases of ovarian cancer specimens, and ovarian cancer cell lines SKOV3, A2780, and COC1. MAGE, GAGE and BAGE genes were not expressed in normal ovarian tissue. In benign tumors, only the MAGE gene was expressed; the expression rate of this gene in benign tumors was 15% (3/20). In ovarian cancer tissues, MAGE-1 and MAGE-3 was highly expressed, with expression rates of 53.7% (22/41) and 36.6% (15/41), while GAGE-1/2 and BAGE had relatively low expression, with rates of 26.8% (11/41) and 14.6% (6/41). In metastatic lesions of ovarian cancer, only MAGE-1 and BAGE were expressed, with expression rates of 28.6% (2/7) and 14.3% (1/7). The positive expression rates of MAGE-1 and MAGE-3 in serous cystadenocarcinoma were significantly higher than that in other types of ovarian cancer (P BAGE was significantly higher in ovarian cancer patients with ascites (P BAGE in ovarian carcinoma cell lines SKOV3, A2780 and COC1 varied, but there was at least one gene expressed in each cell line. Tumor-specific antigen MAGE, BAGE and GAGE may play a role in the occurrence and development of ovarian cancer. These genes can be used as one of the important indicators for early diagnosis, efficacy evaluation and prognostic determination of ovarian cancer.

  10. Treatment Options for Ovarian Low Malignant Potential Tumors

    Science.gov (United States)

    ... tests or procedures are used for staging. Staging laparotomy (a surgical incision made in the wall of ... treatment. Two types of standard treatment are used: Surgery The type of surgery (removing the tumor in ...

  11. Treatment Option Overview (Ovarian Low Malignant Potential Tumors)

    Science.gov (United States)

    ... tests or procedures are used for staging. Staging laparotomy (a surgical incision made in the wall of ... treatment. Two types of standard treatment are used: Surgery The type of surgery (removing the tumor in ...

  12. Serum platelet-derived growth factor and fibroblast growth factor in patients with benign and malignant ovarian tumors

    DEFF Research Database (Denmark)

    Madsen, Christine Vestergaard; Steffensen, Karina Dahl; Olsen, Dorte Aalund

    2012-01-01

    New biological markers with predictive or prognostic value are highly warranted in the treatment of ovarian cancer. The platelet-derived growth factor (PDGF) system and fibroblast growth factor (FGF) system are important components in tumor growth and angiogenesis.......New biological markers with predictive or prognostic value are highly warranted in the treatment of ovarian cancer. The platelet-derived growth factor (PDGF) system and fibroblast growth factor (FGF) system are important components in tumor growth and angiogenesis....

  13. Candidate Tumor-Suppressor Gene DLEC1 Is Frequently Downregulated by Promoter Hypermethylation and Histone Hypoacetylation in Human Epithelial Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Joseph Kwong

    2006-04-01

    Full Text Available Suppression of ovarian tumor growth by chromosome 3p was demonstrated in a previous study. Deleted in Lung and Esophageal Cancer 1 (DLEC1 on 3p22.3 is a candidate tumor suppressor in lung, esophageal, and renal cancers. The potential involvement of DLEC1 in epithelial ovarian cancer remains unknown. In the present study, DLEC1 downregulation was found in ovarian cancer cell lines and primary ovarian tumors. Focus-expressed DLEC1 in two ovarian cancer cell lines resulted in 41% to 52% inhibition of colony formation. No chromosomal loss of chromosome 3p22.3 in any ovarian cancer cell line or tissue was found. Promoter hypermethylation of DLEC1 was detected in ovarian cancer cell lines with reduced DLEC1 transcripts, whereas methylation was not detected in normal ovarian epithelium and DLEC1-expressing ovarian cancer cell lines. Treatment with demethylating agent enhanced DLEC1 expression in 90% (9 of 10 of ovarian cancer cell lines. DLEC1 promoter methylation was examined in 13 high-grade ovarian tumor tissues with DLEC1 downregulation, in which 54% of the tumors showed DLEC1 methylation. In addition, 80% of ovarian cancer cell lines significantly upregulated DLEC1 transcripts after histone deacetylase inhibitor treatment. Therefore, our results suggested that DLEC1 suppressed the growth of ovarian cancer cells and that its downregulation was closely associated with promoter hypermethylation and histone hypoacetylation.

  14. Erlotinib Plus Carboplatin and Paclitaxel in Ovarian Carcinoma

    Science.gov (United States)

    2015-10-29

    Brenner Tumor; Fallopian Tube Cancer; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Undifferentiated Adenocarcinoma; Stage III Ovarian Epithelial Cancer; Stage IV Ovarian Epithelial Cancer

  15. A New Paradigm for Ovarian Sex Cord-Stromal Tumor Development

    Science.gov (United States)

    2017-05-01

    versus controls. Interestingly, a number of genes are associated with folliculogenesis and oogenesis. Further studies will be focused on exploiting the...ovaries and antibodies directed to inhibin alpha (INHA), forkhead box L2 (FOXL2), and DEAD (Asp-Glu-Ala-Asp) box polypeptide 4 (DDX4...not develop ovarian tumors, making them unsuitable for the proposed experiment. Thus, we made a minor modification of the experimental approach to

  16. Aberrations of the p53 tumor suppressor gene in human epithelial ovarian carcinoma.

    Science.gov (United States)

    Kim, J W; Cho, Y H; Kwon, D J; Kim, T E; Park, T C; Lee, J M; Namkoong, S E

    1995-05-01

    Aberrations of the p53 gene in 26 surgical specimens of human epithelial ovarian carcinomas were examined by single-strand conformation polymorphism (SSCP) analysis of polymerase chain reaction (PCR) products. Seven (27%) of the tumors demonstrated a SSCP band shift in exons 4 to 9 of the gene, including 5 in the region encompassing exons 5 and 6, 1 in exon 7, and 1 in the region encompassing exons 8 and 9. Mutations were clustered in exon 5 in highly conserved regions of the p53 gene. All of the abnormal DNA fragments have been further characterized by direct DNA sequencing. These include five missense mutations (five transitions), a one-base-pair deletion introducing, by frameshift, a stop codon further downstream, and a two-base-pair insertion introducing a stop codon downstream by frameshift. Most mutations were base substitutions, and were clustered in exon 5 (71%), especially codons 175 and 179. The aberrations of the p53 gene were only found in tumors of FIGO stages III and IV. Histologic grading was also reviewed with respect to p53 aberrations. The aberrations were absent in well-differentiated carcinomas. The more undifferentiated the primary tumor, the more frequent p53 mutation (P p53 gene were common in epithelial ovarian cancers and p53 aberration may occur late during ovarian cancer evolution.

  17. Level and evaluation of tumor marker CA-125 in ovarian cancer patients in Khyber Pakhtunkhwa, Pakistan.

    Science.gov (United States)

    Ahmad, Bashir; Nawaz, Seema; Ali, Sajid; Bashir, Shumaila; Mahmood, Nourin; Gul, Bushra

    2015-01-01

    Due to the increase in morbidity and mortality rate, cancer has become an alarming threat to the human population worldwide. Since cancer is a progressive disorder, timely diagnosis is necessary to prevent/stop cancer from progressing to a severe stage. In Khyber Paktunkhwa, Pakistan, many tumors are diagnosed with endoscopy and biopsy; rare studies exist regarding the diagnosis and evaluation of ovarian cancer, based on tumor markers like CA-125. The objectives of this study were to investigate and evaluate levels of CA-125 in hospitalized ovarian cancer patients. In this study, a total of 63 admitted patients having ovarian cancer by biopsy were included. The level of CA-125 was determined in the blood of these patients using ELISA technique. Out of 63 patients, the level of CA-125 was high in 52% . The affected individuals were more in the group of 40-60 and the level of CA-125 was comparatively higher in patients having moderately differentiated histology than those having well differentiated and poorly differentiated tumor histology. Moreover, the highest level of CA-125 was present among the patients having serous subtype of carcinoma and the common stage of carcinoma was stage II followed by stage III, I and IV. CA-125 level was high in more than 50% of the total patients. Moreover, CA-125 elevation was more common in serous subtype and stage II cancer patients.

  18. Small RNAs and the competing endogenous RNA network in high grade serous ovarian cancer tumor spread.

    Science.gov (United States)

    Bachmayr-Heyda, Anna; Auer, Katharina; Sukhbaatar, Nyamdelger; Aust, Stefanie; Deycmar, Simon; Reiner, Agnes T; Polterauer, Stephan; Dekan, Sabine; Pils, Dietmar

    2016-06-28

    High grade serous ovarian cancer (HGSOC) is among the most deadly malignancies in women, frequently involving peritoneal tumor spread. Understanding molecular mechanisms of peritoneal metastasis is essential to develop urgently needed targeted therapies. We described two peritoneal tumor spread types in HGSOC apparent during surgery: miliary (numerous millet-sized implants) and non-miliary (few big, bulky implants). The former one is defined by a more epithelial-like tumor cell characteristic with less immune cell reactivity and with significant worse prognosis, even if corrected for typical clinicopathologic factors.23 HGSOC patients were enrolled in this study. Isolated tumor cells from fresh tumor tissues of ovarian and peritoneal origin and from ascites were used for ribosomal RNA depleted RNA and small RNA sequencing. RT-qPCR was used to validate results and an independent cohort of 32 patients to validate the impact on survival. Large and small RNA sequencing data were integrated and a new gene-miRNA set analysis method was developed.Thousands of new small RNAs (miRNAs and piwi-interacting RNAs) were predicted and a 13 small RNA signature was developed to predict spread type from formalin-fixed paraffin-embedded tissues. Furthermore, integrative analyses of RNA sequencing and small RNA sequencing data revealed a global upregulation of the competing endogenous RNA network in tumor tissues of non-miliary compared to miliary spread, i.e. higher expression of circular RNAs and long non-coding RNAs compared to coding RNAs but unchanged abundance of small RNAs. This global deregulated expression pattern could be co-responsible for the spread characteristic, miliary or non-miliary, in ovarian cancer.

  19. [Androgen-producing steroid cell ovarian tumor. Report of a case].

    Science.gov (United States)

    Vadillo Buenfil, M; Ramírez Mendoza, P; Cárdenas Cornejo, I; González Bárcena, D

    2000-06-01

    Ovarian Tumors with Endocrine Repercussion make-up 5% of neoplasms in this gland, occupying the first place are the estrogen-producing tumors, in the second place are the androgen-producing tumors, progesterone, corticosteroids and renin are exceptional. In these tumors' nomenclature has existed a kind of synonyms that create confusion about their histogenesis and their difficult use in the literature. A 23 yr-old woman with opsomenorrhea of several years evolution, secondary amenorrhea, deep voice and progressive hirsutism. Weight: 98.500 kg. Height: 1.74 m. Body Mass Index (BMI): 32.61 (kg/m2). Vellus hair in the face (beard and moustache), android distribution in abdomen, forearms, thighs and legs (Ferriman score of 20), acne and bilateral breast involution. All paraclinic exams were negative. Human chorionic gonadotropin quantification in urine of 24 hours was negative. X-Ray: Right ovarian tumor was demonstrated with pelvic ultrasound and computerized axial tomography of abdomen. Cytogenetic study expressed 46 XX chromosomes. Presurgery endocrinologic studies were: total and free testosterone: 3.55 ng/mL and 14.30 pg/mL, respectively. Insulin: 43.3 microU/mL and C peptide: 5.7 ng/mL. The glucose tolerance test demonstrate intolerance to carbohydrates. During operation, the hormone levels in the right ovarian vein were: total and free testosterone of 2.70 ng/mL and 12.70 pg/mL respectively, which normalized after 12 hours of surgery. Other steroid hormones were normal. After six months of surgery the patient had Ferriman score of 10 and eumenorrhea. Weight: 98.100 kg, glucose tolerance test and basal hormone levels were normal. Electron Microscopy showed characteristic data of a steroid producing tumor without crystalloids of Reinke.

  20. Ovarian cancer linked to lynch syndrome typically presents as early-onset, non-serous epithelial tumors

    DEFF Research Database (Denmark)

    Ketabi, Zohreh; Bartuma, Katarina; Bernstein, Inge

    2011-01-01

    OBJECTIVE: Heredity is a major cause of ovarian cancer and during recent years the contribution from germline mismatch repair (MMR) gene mutations linked to Lynch syndrome has gradually been recognized. METHODS: We characterized clinical features, tumor morphology and mismatch repair defects in all...... ovarian cancers identified in Swedish and Danish Lynch syndrome families. RESULTS: In total, 63 epithelial ovarian cancers developed at mean 48 (range 30-79) years of age with 47% being early stage (FIGO stage I). Histologically, endometrioid (35%) and clear cell (17%) tumors were overrepresented....... The underlying MMR gene mutations in these families affected MSH2 in 49%, MSH6 in 33% and MLH1 in 17%. Immunohistochemical loss of the corresponding MMR protein was demonstrated in 33/36 (92%) tumors analyzed. CONCLUSION: The combined data from our cohorts demonstrate that ovarian cancer associated with Lynch...

  1. Ovarian mixed germ cell tumor with yolk sac and teratomatous components in a dog.

    Science.gov (United States)

    Robinson, Nicholas A; Manivel, J Carlos; Olson, Erik J

    2013-05-01

    Mixed germ cell tumors of the ovary have rarely been reported in veterinary species. A 3-year-old intact female Labrador Retriever dog was presented for lethargy, abdominal distention, and a midabdominal mass. An exploratory laparotomy revealed a large (23 cm in diameter) left ovarian tumor and multiple small (2-3 cm in diameter) pale tan masses on the peritoneum and abdominal surface of the diaphragm. Histological examination of the left ovary revealed a mixed germ cell tumor with a yolk sac component with rare Schiller-Duval bodies and a teratomatous component comprised primarily of neural differentiation. The abdominal metastases were solely comprised of the yolk sac component. The yolk sac component was diffusely immunopositive for cytokeratin with scattered cells reactive for α-fetoprotein and placental alkaline phosphatase. Within the teratomatous component, the neuropil was diffusely immunopositive for S100, neuron-specific enolase, and neurofilaments with a few glial fibrillary acidic protein immunopositive cells. Ovarian germ cell tumors may be pure and consist of only 1 germ cell element or may be mixed and include more than 1 germ cell element, such as teratoma and yolk sac tumor.

  2. Differences in pteridine urinary levels in patients with malignant and benign ovarian tumors in comparison with healthy individuals.

    Science.gov (United States)

    Zvarik, M; Martinicky, D; Hunakova, L; Sikurova, L

    2015-12-01

    Pteridines belong to a class of fluorescent metabolites that are excreted by humans in urine and their concentrations can reflect various pathophysiological states. We quantified the differences in urinary pteridine levels in patients with malignant and benign ovarian tumors and in healthy individuals. Urine samples were centrifuged and supernatants were oxidized by MnO2 before analysis. Levels of neopterin, biopterin, and pterin were assessed by fluorescence analysis of human urine after HPLC separation. We have revealed that the median neopterin levels were higher in urine samples from patients with malignant (0.226 μmol/mmol creatinine) and benign ovarian tumors (0.150 μmol/mmol creatinine) than in healthy subjects (0.056 μmol/mmol creatinine). The median neopterin levels of patients with malignant tumors were higher (1.5-times) than in patients with benign tumors. The median biopterin level in urine of patients with benign ovarian tumors (0.268 μmol/mmol creatinine) was found to be very close to the level in patients with malignant ovarian tumors (0.239 μmol/mmol creatinine), and both were higher than in healthy samples (0.096 μmol/mmol creatinine). The levels of urine pterin followed a pattern similar to neopterin levels for both ovarian tumors, but their concentrations were about three times lower than neopterin levels. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Diagnostic performance of MR imaging findings and quantitative values in the differentiation of seromucinous borderline tumour from endometriosis-related malignant ovarian tumour

    Energy Technology Data Exchange (ETDEWEB)

    Kurata, Yasuhisa; Kido, Aki; Moribata, Yusaku; Kameyama, Kyoko; Himoto, Yuki; Togashi, Kaori [Kyoto University Graduate School of Medicine, Department of Diagnostic Imaging and Nuclear Medicine, 54 Kawahara-cho, Shogoin, Sakyoku, Kyoto (Japan); Minamiguchi, Sachiko [Kyoto University Graduate School of Medicine, Department of Diagnostic Pathology, 54 Kawahara-cho, Shogoin, Sakyoku, Kyoto (Japan); Konishi, Ikuo [Kyoto University Graduate School of Medicine, Department of Gynecology and Obstetrics, 54 Kawahara-cho, Shogoin, Sakyoku, Kyoto (Japan)

    2017-04-15

    To evaluate the diagnostic performance of quantitative values and MRI findings for differentiating seromucinous borderline tumours (SMBTs) from endometriosis-related malignant ovarian tumours (MT). This retrospective study examined 19 lesions from SMBT and 84 lesions from MT. The following quantitative values were evaluated using receiver-operating characteristic analysis: overall and solid portion sizes, fluid signal intensity (SI), degree of contrast-enhancement, and mean and minimum apparent diffusion coefficient (ADC) values of the solid portion. Two radiologists independently evaluated four MRI findings characteristic of SMBT, fluid SI on the T1-weighted image and SI of the solid portion on diffusion-weighted image. The diagnostic values of these findings and interobserver agreement were assessed. For diagnosing SMBT, the mean ADC value of the solid portion showed the greatest area under the curve (0.860) (cut-off value: 1.31 x 10{sup -3} mm{sup 2}/s, sensitivity: 1.00, specificity: 0.61). The T2-weighted image (T2WI) high SI solid portion was the most useful finding, with high specificity and interobserver agreement (sensitivity, 0.58; specificity, 0.95-0.96, kappa = 0.96), followed by T2WI low SI core (sensitivity, 0.48-0.63; specificity, 0.98, kappa = 0.68). Mean ADC values of the solid portion, T2WI high SI solid portion, and T2WI low SI core were useful for differentiating SMBT from MT. (orig.)

  4. Metastatic liver tumor from cystic ovarian carcinomas. CT and MRI appearance

    International Nuclear Information System (INIS)

    Tang, Yi; Yamashita, Yasuyuki; Ogata, Ichiro; Namimoto, Tomohiro; Abe, Yasuko; Urata, Joji; Takahashi, Mutsumasa

    1999-01-01

    The initial and follow-up CT and MRI images of ten patients with hepatic metastases from ovarian tumors were retrospectively analyzed to establish their features and sequential changes in appearance. Ten patients with hepatic metastasis from ovarian tumors received initial and follow-up CT and MRI examinations. Six patients were followed up every two to three weeks before surgical tumor resection. Both CT and MR images were analyzed by two radiologists. A total of fourteen lesions were detected by CT and MRI in 10 patients. All 14 lesions were demonstrated as areas of marked hyperintensity on T2-weighted MRI. Eleven cyst-like tumors were demonstrated as round or oval low density lesions on CT and as areas of hypointensity on T1-weighted imaging. Three lesions were shown as solid masses with slightly low attenuation at the initial CT examination and slightly low or iso-intensity areas on T1-weighted imaging, and these lesions showed early peripheral globular enhancement and delayed enhancement on contrast-enhanced CT and MR imaging. Cystic formation was observed two to three weeks later after initial study in all the 3 solid lesions. Rapid subcapsular effusion, which showed obvious enhancement on delayed Gd-DTPA enhanced MR imaging, was observed in two patients. The hepatic metastatic tumor from cystic ovarian carcinoma may manifest as a well-defined cystic lesion or as a solid mass, and the solid mass shows delayed enhancement on contrast-enhanced CT and MR imaging. Furthermore, rapid cystic formation and rapid subcapsular extension is frequently seen. (author)

  5. Ovarian Sertoli-Leydig Cell Tumor with Elevated Inhibin B As a Cause of Secondary Amenorrhea in Adolescents with Germline DICER1 Mutation

    Science.gov (United States)

    2017-04-06

    FROM: 59 MDW/SGVU SUBJECT: Professional Presentation Approval 6 APR 2017 1. Your paper, entitled Ovarian Sertoli-Leydig Cell Tumor with Elevated...must be submitted for review and approval.) 6. TITLE OF MATERIAL TO BE PUBLISHED OR PRESENTED: Ovarian Sertoli-Leydig cell tumor w i th elevated...DATE Page 3 of 3 Pages Abstract Background: Although uncommon in children, ovarian tumors can retain endocrine function that disrupts normal feedback

  6. The utility of serum N-ERC/mesothelin as a biomarker of ovarian carcinoma.

    Science.gov (United States)

    Saeki, Harumi; Hashizume, Akane; Izumi, Hiroshi; Suzuki, Fujihiko; Ishi, Kazuhisa; Nojima, Michio; Maeda, Masahiro; Hino, Okio

    2012-10-01

    Ovarian carcinoma has been difficult to diagnose at an early stage. Recently, it has been recognized that the measurement of blood N-ERC/mesothelin levels aids early detection in and postoperative therapeutic monitoring of patients with mesothelioma, who have been exposed to asbestos. ERC/mesothelin has also been reported to be expressed in ovarian carcinoma. We determined serum N-ERC/mesothelin levels in patients with ovarian carcinoma using an enzyme-linked immunosorbent assay (ELISA). In addition, we immunohistochemically evaluated surgically resected specimens for C-ERC/mesothelin expression. As a result, of the 32 patients with ovarian tumors (18 carcinoma, 2 borderline tumors), one patient with serous adenocarcinoma showed increased N-ERC/ mesothelin levels. Immunohistochemically, of the 20 ovarian tumor (carcinoma and borderline tumor) specimens evaluated for serum N-ERC/mesothelin, 9 (45.0%) were positive for C-ERC/mesothelin. The C-ERC/mesothelin-positive specimens were found to be serous and clear cell adenocarcinomas. If serum N-ERC/mesothelin, which is considered useful for early detection in and therapeutic monitoring of patients with mesothelioma, may also be used for ovarian carcinoma monitoring, it may be a valuable serum tumor marker for the early detection of ovarian carcinoma.

  7. Palliative Care in Improving Quality of Life and Symptoms in Patients With Stage III-IV Pancreatic or Ovarian Cancer

    Science.gov (United States)

    2014-12-18

    Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Pancreatic Cancer; Stage III Pancreatic Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Pancreatic Cancer

  8. Mature Ovarian Teratoma with Carcinoid Tumor in a 28-Year-Old Patient

    Directory of Open Access Journals (Sweden)

    Stamatios Petousis

    2013-01-01

    Full Text Available Introduction. Coexistence of carcinoid tumor inside a mature cystic teratoma is an extremely rare phenomenon, especially in young women. We present the case of a 28-year-old woman diagnosed with a right ovarian carcinoid and treated uneventfully with conservative surgical approach. Case Report. A 28-year-old woman, gravid 0, parity 0, presented to our department for her annual gynecological examination and Pap smear test. During her examination, a mobile cystic mass was detected in the right lower abdomen. Ultrasound indicated a right ovarian mass 10.5 × 6.3 cm, confirmed by CT scan. Further investigation revealed AFP levels (1539 ng/mL. The ovarian mass was excised by laparoscopy, leaving intact the remaining right ovary. Frozen sections showed a mature cystic teratoma. However, paraffin sections revealed the presence of a small carcinoid within the teratoma’s gastric-type mucosa. The patient was set to a close followup. Nine months postoperatively, ultrasound pelvis imaging and CT scan of the abdomen as well as serum tumor markers have shown no evidence of recurrence disease. Conclusion. Despite the weak evidence, fertility spare surgical approach for women wanting to preserve their genital tract might be a reasonable option.

  9. Tumor-associated auto-antibodies as early detection markers for ovarian cancer?

    DEFF Research Database (Denmark)

    Kaaks, Rudolf; Fortner, Renée Turzanski; Hüsing, Anika

    2018-01-01

    .08-0.40] for CTAG1A, CTAG2 and NUDT1 to 0.23 [0.10-0.44] for P53 (0.33 [0.11-0.68] for high-grade serous tumors). However, at longer lead-times the ability of these AAb markers to distinguish future ovarian cancer cases from controls declined rapidly; at lead times >1 year, SE98 estimates were close to zero (all......Immuno-proteomic screening has identified several tumor-associated auto-antibodies (AAb) that may have diagnostic capacity for invasive epithelial ovarian cancer, with AAbs to P53 proteins and cancer-testis antigens (CTAGs) as prominent examples. However, the early detection potential of these AAbs...... under usual care. CA125 was measured using electrochemo-luminiscence. Diagnostic discrimination statistics were calculated by strata of lead-time between blood collection and diagnosis. With lead times ≤6 months, ovarian cancer detection sensitivity at 0.98 specificity (SE98) varied from 0.19 [95% CI 0...

  10. Heterogeneity of tumor chemosensitivity in ovarian epithelial cancer revealed using the adenosine triphosphate-tumor chemosensitivity assay.

    Science.gov (United States)

    Zhang, Jin; Li, Hongxia

    2015-05-01

    Ovarian cancer has a poor prognosis, primarily due to the heterogeneity in chemosensitivity among patients. In the present study, this heterogeneity was evaluated in ovarian epithelial cancer (OEC) using an in vitro adenosine triphosphate tumor chemosensitivity assay (ATP-TCA). Specimens were collected from 80 patients who underwent cytoreductive surgery. Viable ovarian cancer cells obtained from malignant tissues were tested for sensitivity to paclitaxel (PTX), carboplatin (CBP), topotecan (TPT), gemcitabine (GEM), docetaxel (TXT), etoposide, bleomycin and 4-hydroperoxycyclophosphamide using ATP-TCA. The sensitivity, specificity, positive predictive value and negative predictive value for the clinical chemotherapy sensitivity of OEC were 88.6, 77.8, 83 and 84.8%, respectively. PTX demonstrated the highest sensitivity of all agents tested (82.5% in all specimens, 85.7% in recurrent specimens), followed by CBP (58.8 and 60.7%, respectively). The sensitivities to PTX and docetaxel (PIII) or low-differentiated specimens, respectively. The present study indicated that ATP-TCA is an effective method for guiding the choice of chemotherapy drugs. Notable heterogeneity of chemosensitivity was observed in the OEC specimens.

  11. Heterogeneity of tumor chemosensitivity in ovarian epithelial cancer revealed using the adenosine triphosphate-tumor chemosensitivity assay

    Science.gov (United States)

    ZHANG, JIN; LI, HONGXIA

    2015-01-01

    Ovarian cancer has a poor prognosis, primarily due to the heterogeneity in chemosensitivity among patients. In the present study, this heterogeneity was evaluated in ovarian epithelial cancer (OEC) using an in vitro adenosine triphosphate tumor chemosensitivity assay (ATP-TCA). Specimens were collected from 80 patients who underwent cytoreductive surgery. Viable ovarian cancer cells obtained from malignant tissues were tested for sensitivity to paclitaxel (PTX), carboplatin (CBP), topotecan (TPT), gemcitabine (GEM), docetaxel (TXT), etoposide, bleomycin and 4-hydroperoxycyclophosphamide using ATP-TCA. The sensitivity, specificity, positive predictive value and negative predictive value for the clinical chemotherapy sensitivity of OEC were 88.6, 77.8, 83 and 84.8%, respectively. PTX demonstrated the highest sensitivity of all agents tested (82.5% in all specimens, 85.7% in recurrent specimens), followed by CBP (58.8 and 60.7%, respectively). The sensitivities to PTX and docetaxel (P<0.001) were correlated, in addition to those of CBP, TPT and GEM (P<0.001). Early-stage (I/II) and high- to mildly-differentiated OEC specimens revealed a lower chemosensitivity than advanced-stage (III) or low-differentiated specimens, respectively. The present study indicated that ATP-TCA is an effective method for guiding the choice of chemotherapy drugs. Notable heterogeneity of chemosensitivity was observed in the OEC specimens. PMID:26137074

  12. Tumor-infiltrating T cells correlate with NY-ESO-1-specific autoantibodies in ovarian cancer.

    Science.gov (United States)

    Milne, Katy; Barnes, Rebecca O; Girardin, Adam; Mawer, Melanie A; Nesslinger, Nancy J; Ng, Alvin; Nielsen, Julie S; Sahota, Robert; Tran, Eric; Webb, John R; Wong, May Q; Wick, Darin A; Wray, Andrew; McMurtrie, Elissa; Köbel, Martin; Kalloger, Steven E; Gilks, C Blake; Watson, Peter H; Nelson, Brad H

    2008-01-01

    Tumor-infiltrating CD8+ T cells are correlated with prolonged progression-free and overall survival in epithelial ovarian cancer (EOC). A significant fraction of EOC patients mount autoantibody responses to various tumor antigens, however the relationship between autoantibodies and tumor-infiltrating T cells has not been investigated in EOC or any other human cancer. We hypothesized that autoantibody and T cell responses may be correlated in EOC and directed toward the same antigens. We obtained matched serum and tumor tissue from 35 patients with high-grade serous ovarian cancer. Serum samples were assessed by ELISA for autoantibodies to the common tumor antigen NY-ESO-1. Tumor tissue was examined by immunohistochemistry for expression of NY-ESO-1, various T cell markers (CD3, CD4, CD8, CD25, FoxP3, TIA-1 and Granzyme B) and other immunological markers (CD20, MHC class I and MHC class II). Lymphocytic infiltrates varied widely among tumors and included cells positive for CD3, CD8, TIA-1, CD25, FoxP3 and CD4. Twenty-six percent (9/35) of patients demonstrated serum IgG autoantibodies to NY-ESO-1, which were positively correlated with expression of NY-ESO-1 antigen by tumor cells (r = 0.57, p = 0.0004). Autoantibodies to NY-ESO-1 were associated with increased tumor-infiltrating CD8+, CD4+ and FoxP3+ cells. In an individual HLA-A2+ patient with autoantibodies to NY-ESO-1, CD8+ T cells isolated from solid tumor and ascites were reactive to NY-ESO-1 by IFN-gamma ELISPOT and MHC class I pentamer staining. We demonstrate that tumor-specific autoantibodies and tumor-infiltrating T cells are correlated in human cancer and can be directed against the same target antigen. This implies that autoantibodies may collaborate with tumor-infiltrating T cells to influence clinical outcomes in EOC. Furthermore, serological screening methods may prove useful for identifying clinically relevant T cell antigens for immunotherapy.

  13. Tumor-infiltrating T cells correlate with NY-ESO-1-specific autoantibodies in ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Katy Milne

    Full Text Available BACKGROUND: Tumor-infiltrating CD8+ T cells are correlated with prolonged progression-free and overall survival in epithelial ovarian cancer (EOC. A significant fraction of EOC patients mount autoantibody responses to various tumor antigens, however the relationship between autoantibodies and tumor-infiltrating T cells has not been investigated in EOC or any other human cancer. We hypothesized that autoantibody and T cell responses may be correlated in EOC and directed toward the same antigens. METHODOLOGY AND PRINCIPAL FINDINGS: We obtained matched serum and tumor tissue from 35 patients with high-grade serous ovarian cancer. Serum samples were assessed by ELISA for autoantibodies to the common tumor antigen NY-ESO-1. Tumor tissue was examined by immunohistochemistry for expression of NY-ESO-1, various T cell markers (CD3, CD4, CD8, CD25, FoxP3, TIA-1 and Granzyme B and other immunological markers (CD20, MHC class I and MHC class II. Lymphocytic infiltrates varied widely among tumors and included cells positive for CD3, CD8, TIA-1, CD25, FoxP3 and CD4. Twenty-six percent (9/35 of patients demonstrated serum IgG autoantibodies to NY-ESO-1, which were positively correlated with expression of NY-ESO-1 antigen by tumor cells (r = 0.57, p = 0.0004. Autoantibodies to NY-ESO-1 were associated with increased tumor-infiltrating CD8+, CD4+ and FoxP3+ cells. In an individual HLA-A2+ patient with autoantibodies to NY-ESO-1, CD8+ T cells isolated from solid tumor and ascites were reactive to NY-ESO-1 by IFN-gamma ELISPOT and MHC class I pentamer staining. CONCLUSION AND SIGNIFICANCE: We demonstrate that tumor-specific autoantibodies and tumor-infiltrating T cells are correlated in human cancer and can be directed against the same target antigen. This implies that autoantibodies may collaborate with tumor-infiltrating T cells to influence clinical outcomes in EOC. Furthermore, serological screening methods may prove useful for identifying clinically relevant

  14. Prognostic impact of normalization of serum tumor markers following neoadjuvant chemotherapy in patients with borderline resectable pancreatic carcinoma with arterial contact.

    Science.gov (United States)

    Murakami, Yoshiaki; Uemura, Kenichiro; Sudo, Takeshi; Hashimoto, Yasushi; Kondo, Naru; Nakagawa, Naoya; Okada, Kenjiro; Takahashi, Shinya; Sueda, Taijiro

    2017-04-01

    The survival benefit of neoadjuvant therapy for patients with borderline resectable pancreatic carcinoma has been reported recently. However, prognostic factors for this strategy have not been clearly elucidated. The aim of this study was to clarify prognostic factors for patients with borderline resectable pancreatic carcinoma who received neoadjuvant chemotherapy. Medical records of 66 patients with pancreatic carcinoma with arterial contact who intended to undergo tumor resection following neoadjuvant chemotherapy were analyzed retrospectively. Prognostic factors were investigated by analyzing the clinicopathological factors with univariate and multivariate survival analyses. Gemcitabine plus S-1 was generally used as neoadjuvant chemotherapy. The objective response rate was 24%, and normalization of serum tumor markers following neoadjuvant chemotherapy was achieved in 29 patients (44%). Of the 66 patients, 60 patients underwent tumor resection and the remaining six patients did not due to distant metastases following neoadjuvant chemotherapy. For all 66 patients, overall 1-, 2-, and 5-year survival rates were 87.8, 54.5, and 20.5%, respectively (median survival time, 27.1 months) and multivariate analysis revealed that normalization of serum tumor markers was found to be an independent prognostic factor of better overall survival (P = 0.023). Moreover, for 60 patients who undergo tumor resection, normalization of serum tumor markers (P = 0.005) was independently associated with better overall survival by multivariate analysis. Patients with pancreatic carcinoma with arterial contact who undergo neoadjuvant chemotherapy and experience normalization of serum tumor markers thereafter may be good candidates for tumor resection.

  15. Ovarian serous carcinoma: relationship of p53 and bcl-2 with tumor angiogenesis and VEGF expression.

    Science.gov (United States)

    Crasta, Julian A; Mishra, Suniti; Vallikad, Elizabeth

    2011-11-01

    The aim of the study was to assess the microvessel density (MVD) and vascular endothelial growth factor (VEGF) expression in ovarian serous carcinoma and to examine their relation with apoptosis.Paraffin-embedded specimens of 41 cases of ovarian serous carcinomas were evaluated by immunohistochemistry for VEGF, p53, and bcl-2 expression. MVD was assessed with CD31 staining. We investigated the association of tumor angiogenesis (MVD and VEGF) with clinicopathologic factors, p53 overexpression, and bcl-2 expression.There was a significant correlation between high MVD and suboptimal debulking and advanced stage disease. A significant negative correlation was expressed between bcl-2 and VEGF expression. In univariate analysis, only stage had a significant impact on disease-free survival.The results of this study suggest that higher degree of angiogenesis is associated with suboptimal debulking and advanced-stage disease. Expression of VEGF had negative association with VEGF expression.

  16. MHC class I-presented tumor antigens identified in ovarian cancer by immunoproteomic analysis are targets for T-cell responses against breast and ovarian cancer.

    Science.gov (United States)

    Morse, Michael A; Secord, Angeles A; Blackwell, Kimberly; Hobeika, Amy C; Sinnathamby, Gomathinayagam; Osada, Takuya; Hafner, Julie; Philip, Mohan; Clay, Timothy M; Lyerly, H Kim; Philip, Ramila

    2011-05-15

    The purpose of this study is to test whether peptide epitopes chosen from among those naturally processed and overpresented within MHC molecules by malignant, but not normal cells, when formulated into cancer vaccines, could activate antitumor T-cell responses in humans. Mixtures of human leukocyte antigen A2 (HLA-A2)-binding ovarian cancer-associated peptides were used to activate naive T cells to generate antigen-specific T cells that could recognize ovarian and breast cancers in vitro. Combinations of these peptides (0.3 mg of each peptide or 1 mg of each peptide) were formulated into vaccines in conjunction with Montanide ISA-51 and granulocyte monocyte colony stimulating factor which were used to vaccinate patients with ovarian and breast cancer without evidence of clinical disease in parallel pilot clinical trials. T cells specific for individual peptides could be generated in vitro by using mixtures of peptides, and these T cells recognized ovarian and breast cancers but not nonmalignant cells. Patient vaccinations were well tolerated with the exception of local erythema and induration at the injection site. Nine of the 14 vaccinated patients responded immunologically to their vaccine by inducing peptide-specific T-cell responses that were capable of recognizing HLA-matched breast and ovarian cancer cells. Mixtures of specific peptides identified as naturally presented on cancer cells and capable of activating tumor-specific T cells in vitro also initiate or augment immune responses toward solid tumors in cancer patients. ©2011 AACR.

  17. Molecular characteristics of malignant ovarian germ cell tumors and comparison with testicular counterparts

    DEFF Research Database (Denmark)

    Kraggerud, Sigrid Marie; Hoei-Hansen, Christina E; Alagaratnam, Sharmini

    2013-01-01

    This review focuses on the molecular characteristics and development of rare malignant ovarian germ cell tumors (mOGCTs). We provide an overview of the genomic aberrations assessed by ploidy, cytogenetic banding, and comparative genomic hybridization. We summarize and discuss the transcriptome......, endocrinological influences, and pathogenesis, as is the GCT origin in patients with disorders of sex development. Integrated molecular profiles of the 3 main histological subtypes, dysgerminoma (DG), yolk sac tumor (YST), and immature teratoma (IT), are presented. DGs show genomic aberrations comparable to TGCT...... their similarity to pluripotent precursor cells (primordial germ cells, PGCs) and other stem cells. This similarity combined with the process of ovary development, explain why mOGCTs present so early in life, and with greater histological complexity, than most somatic solid tumors....

  18. Role of the immune system in the peritoneal tumor spread of high grade serous ovarian cancer.

    Science.gov (United States)

    Auer, Katharina; Bachmayr-Heyda, Anna; Sukhbaatar, Nyamdelger; Aust, Stefanie; Schmetterer, Klaus G; Meier, Samuel M; Gerner, Christopher; Grimm, Christoph; Horvat, Reinhard; Pils, Dietmar

    2016-09-20

    The immune system plays a critical role in cancer progression and overall survival. Still, it is unclear if differences in the immune response are associated with different patterns of tumor spread apparent in high grade serous ovarian cancer patients and previously described by us. In this study we aimed to assess the role of the immune system in miliary (widespread, millet-sized lesions) and non-miliary (bigger, exophytically growing implants) tumor spread. To achieve this we comprehensively analyzed tumor tissues, blood, and ascites from 41 patients using immunofluorescence, flow cytometry, RNA sequencing, multiplexed immunoassays, and immunohistochemistry. Results showed that inflammation markers were systemically higher in miliary. In contrast, in non-miliary lymphocyte and monocyte/macrophage infiltration into the ascites was higher as well as the levels of PD-1 expression in tumor associated cytotoxic T-lymphocytes and PD-L1 expression in tumor cells. Furthermore, in ascites of miliary patients more epithelial tumor cells were present compared to non-miliary, possibly due to the active down-regulation of anti-tumor responses by B-cells and regulatory T-cells. Summarizing, adaptive immune responses prevailed in patients with non-miliary spread, whereas in patients with miliary spread a higher involvement of the innate immune system was apparent while adaptive responses were counteracted by immune suppressive cells and factors.

  19. A Case of Giant Borderline Phyllodes Tumor of the Breast Associated with Hypoglycemia.

    Science.gov (United States)

    Saito, Yuki; Suzuki, Yasuhiro; Inomoto, Chie; Kumaki, Nobue; Yokoyama, Kozue; Ogiya, Rin; Oshitanai, Risa; Terao, Mayako; Tsuda, Banri; Morioka, Tooru; Niikura, Naoki; Okamura, Takuho; Masuda, Shinobu; Tokuda, Yutaka

    2016-09-20

    We report a patient with a giant phyllodes tumor of the right breast associated with a hypoglycemic attack. A 48-year-old woman experienced a loss of consciousness and was transferred via ambulance to our hospital emergency department. Upon arrival, her blood glucose level was 26 mg/dl, and a giant tumor (>20 cm in diameter) with skin ulceration was observed on the right breast. Core needle biopsy led to a histological diagnosis of a phyllodes tumor of the breast. Ultrasonography and computed tomography detected neither distant metastasis nor a pancreatic endocrine tumor. Her preoperative serum insulin-like growth factor (IGF)-II and insulin levels were 1,330 ng/ml (normal range, 519-1067 ng/ml) and phyllodes tumor and normal breast tissue were 10,600 ng/Wg (wet weight in grams) and 855 ng/Wg. We conclude from these findings that the hypoglycemic attack was related to the elevated IGF-II level in the giant phyllodes tumor of the breast.

  20. Interleukin 16- (IL-16-) Targeted Ultrasound Imaging Agent Improves Detection of Ovarian Tumors in Laying Hens, a Preclinical Model of Spontaneous Ovarian Cancer.

    Science.gov (United States)

    Barua, Animesh; Yellapa, Aparna; Bahr, Janice M; Adur, Malavika K; Utterback, Chet W; Bitterman, Pincas; Basu, Sanjib; Sharma, Sameer; Abramowicz, Jacques S

    2015-01-01

    Limited resolution of transvaginal ultrasound (TVUS) scanning is a significant barrier to early detection of ovarian cancer (OVCA). Contrast agents have been suggested to improve the resolution of TVUS scanning. Emerging evidence suggests that expression of interleukin 16 (IL-16) by the tumor epithelium and microvessels increases in association with OVCA development and offers a potential target for early OVCA detection. The goal of this study was to examine the feasibility of IL-16-targeted contrast agents in enhancing the intensity of ultrasound imaging from ovarian tumors in hens, a model of spontaneous OVCA. Contrast agents were developed by conjugating biotinylated anti-IL-16 antibodies with streptavidin coated microbubbles. Enhancement of ultrasound signal intensity was determined before and after injection of contrast agents. Following scanning, ovarian tissues were processed for the detection of IL-16 expressing cells and microvessels. Compared with precontrast, contrast imaging enhanced ultrasound signal intensity significantly in OVCA hens at early (P ultrasound signals in OVCA hens were associated with increased frequencies of IL-16 expressing cells and microvessels. These results suggest that IL-16-targeted contrast agents improve the visualization of ovarian tumors. The laying hen may be a suitable model to test new imaging agents and develop targeted anti-OVCA therapeutics.

  1. Interleukin 16- (IL-16- Targeted Ultrasound Imaging Agent Improves Detection of Ovarian Tumors in Laying Hens, a Preclinical Model of Spontaneous Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Animesh Barua

    2015-01-01

    Full Text Available Limited resolution of transvaginal ultrasound (TVUS scanning is a significant barrier to early detection of ovarian cancer (OVCA. Contrast agents have been suggested to improve the resolution of TVUS scanning. Emerging evidence suggests that expression of interleukin 16 (IL-16 by the tumor epithelium and microvessels increases in association with OVCA development and offers a potential target for early OVCA detection. The goal of this study was to examine the feasibility of IL-16-targeted contrast agents in enhancing the intensity of ultrasound imaging from ovarian tumors in hens, a model of spontaneous OVCA. Contrast agents were developed by conjugating biotinylated anti-IL-16 antibodies with streptavidin coated microbubbles. Enhancement of ultrasound signal intensity was determined before and after injection of contrast agents. Following scanning, ovarian tissues were processed for the detection of IL-16 expressing cells and microvessels. Compared with precontrast, contrast imaging enhanced ultrasound signal intensity significantly in OVCA hens at early (P<0.05 and late stages (P<0.001. Higher intensities of ultrasound signals in OVCA hens were associated with increased frequencies of IL-16 expressing cells and microvessels. These results suggest that IL-16-targeted contrast agents improve the visualization of ovarian tumors. The laying hen may be a suitable model to test new imaging agents and develop targeted anti-OVCA therapeutics.

  2. Intensive expression of Bmi-1 is a new independent predictor of poor outcome in patients with ovarian carcinoma

    International Nuclear Information System (INIS)

    Yang, Guo-Fen; Xie, Dan; He, Wei-Peng; Cai, Mu-Yan; He, Li-Ru; Luo, Jun-Hang; Deng, Hai-Xia; Guan, Xin-Yuan; Zeng, Mu-Sheng; Zeng, Yi-Xin

    2010-01-01

    It has been suggested that the B-cell specific moloney leukemia virus insertion site 1 (Bmi-1) gene plays an oncogenic role in several types of human cancer, but the status of Bmi-1 amplification and expression in ovarian cancer and its clinical/prognostic significance are unclear. The methods of immunohistochemistry and fluorescence in situ hybridization were utilized to examine protein expression and amplification of Bmi-1 in 30 normal ovaries, 30 ovarian cystadenomas, 40 borderline ovarian tumors and 179 ovarian carcinomas. Intensive expression of Bmi-1 was detected in none of the normal ovaries, 3% cystadenomas, 10% borderline tumors, and 37% ovarian carcinomas, respectively. Amplification of Bmi-1 was detected in 8% of ovarian carcinomas. In ovarian carcinomas, significant positive associations were found between intensive expression of Bmi-1 and the tumors ascending histological grade, later pT/pN/pM and FIGO stages (P < 0.05). In univariate survival analysis of the ovarian carcinoma cohorts, a significant association of intensive expression of Bmi-1 with shortened patient survival (mean 49.3 months versus 100.3 months, p < 0.001) was demonstrated. Importantly, Bmi-1 expression provided significant independent prognostic parameters in multivariate analysis (p = 0.005). These findings provide evidence that intensive expression of Bmi-1 might be important in the acquisition of an invasive and/or aggressive phenotype of ovarian carcinoma, and serve as a independent biomarker for shortened survival time of patients

  3. The construction of cDNA library and the screening of related antigen of ascitic tumor cells of ovarian cancer.

    Science.gov (United States)

    Hou, Q; Chen, K; Shan, Z

    2015-01-01

    To construct the cDNA library of the ascites tumor cells of ovarian cancer, which can be used to screen the related antigen for the early diagnosis of ovarian cancer and therapeutic targets of immune treatment. Four cases of ovarian serous cystadenocarcinoma, two cases of ovarian mucinous cystadenocarcinoma, and two cases of ovarian endometrial carcinoma in patients with ascitic tumor cells which were used to construct the cDNA library. To screen the ovarian cancer antigen gene, evaluate the enzyme, and analyze nucleotide sequence, serological analysis of recombinant tumor cDNA expression libraries (SEREX) and suppression subtractive hybridization technique (SSH) techniques were utilized. The detection method of recombinant expression-based serological mini-arrays (SMARTA) was used to detect the ovarian cancer antigen and the positive reaction of 105 cases of ovarian cancer patients and 105 normal women's autoantibodies correspondingly in serum. After two rounds of serologic screening and glycosides sequencing analysis, 59 candidates of ovarian cancer antigen gene fragments were finally identified, which corresponded to 50 genes. They were then divided into six categories: (1) the homologous genes which related to the known ovarian cancer genes, such as BARD 1 gene, etc; (2) the homologous genes which were associated with other tumors, such as TM4SFI gene, etc; (3) the genes which were expressed in a special organization, such as ILF3, FXR1 gene, etc; (4) the genes which were the same with some protein genes of special function, such as TIZ, ClD gene; (5) the homologous genes which possessed the same source with embryonic genes, such as PKHD1 gene, etc; (6) the remaining genes were the unknown genes without the homologous sequence in the gene pool, such as OV-189 genes. SEREX technology combined with SSH method is an effective research strategy which can filter tumor antigen with high specific character; the corresponding autoantibodies of TM4SFl, ClD, TIZ, BARDI

  4. The role of preoperative serum cancer antigen 125 in malignant ovarian germ cell tumors

    Directory of Open Access Journals (Sweden)

    Ju-Hyun Kim

    2018-04-01

    Full Text Available Objective: To determine the role of preoperative serum cancer antigen 125 (CA 125 in malignant ovarian germ cell tumors (MOGCTs. Materials and methods: Using information from medical databases of Asan Medical Center (Seoul, Korea, we investigated 161 patients with histologically diagnosed MOGCTs and whose preoperative serum CA 125 had been checked. We determined the optimal cutoff value of CA 125 as > 249.5 U/mL in MOGCTs using a receiver operating characteristic curve. Results: The median patient age was 24 years (range, 6–52 years. The most common histologic type was immature teratoma. Most patients had stage I disease. Thirty-two patients (19.9% had elevated preoperative serum CA 125 levels over 249.5 U/mL. On univariate analysis, tumor size, advanced stage, the presence of ascites, ovarian surface involvement, and tumor rupture were significantly associated with elevated preoperative CA 125 levels (>249.5 U/mL. In the median follow-up time of 87 months (range, 9–271 months, 14 patients had a recurrence, and 5 died of the disease. Patients with an elevated serum preoperative CA 125 level (>249.5 U/mL had poorer disease-free survival, but this was not statistically significant. However, elevated preoperative CA 125 (>249.5 U/mL was significantly associated with poorer overall survival. Conclusions: Elevated preoperative serum CA 125 may have prognostic value in patients with MOGCTs. Keywords: CA-125 antigen, Ovarian germ cell cancer, Prognosis

  5. Overexpression of karyopherin 2 in human ovarian malignant germ cell tumor correlates with poor prognosis.

    Directory of Open Access Journals (Sweden)

    Li He

    Full Text Available BACKGROUND: The aim of this study was to identify a biomarker useful in the diagnosis and therapy of ovarian malignant germ cell tumor (OMGCT. METHODS: The karyopherin 2 (KPNA2 expression in OMGCT and normal ovarian tissue was determined by standard gene microarray assays, and further validated by a quantitative RT-PCR and immunohistochemistry. The correlation between KPNA2 expression in OMGCT and certain clinicopathological features were analyzed. Expression of SALL4, a stem cell marker, was also examined in comparison with KPNA2. RESULTS: KPNA2 was found to be over-expressed by approximately eight-fold in yolk sac tumors and immature teratomas compared to normal ovarian tissue by microarray assays. Overexpression was detected in yolk sac tumors, immature teratomas, dysgerminomas, embryonal carcinomas, mature teratomas with malignant transformation and mixed ovarian germ cell tumors at both the transcription and translation levels. A positive correlation between KPNA2 and SALL4 expression at both the transcription level (R = 0.5120, P = 0.0125, and the translation level (R = 0.6636, P<0.0001, was presented. Extensive expression of KPNA2 was positively associated with pathologic type, recurrence and uncontrolled, ascitic fluid presence, suboptimal cytoreductive surgery necessity, resistance/refraction to initial chemotherapy, HCG level and SALL4 level in OMGCT patients. KPNA2 was found to be an independent factor for 5-year disease-free survival (DFS of OMGCT (P = 0.02. The 5-year overall survival (OS and DFS rate for KPNA2-low expression patients (88% and 79%, n = 48 were significantly higher than the OS and DFS rate for KPNA2-high expression patients (69% and 57.1%, n = 42(P = 0.0151, P = 0.0109, respectively. The 5-year OS and DFS rate for SALL4-low expression patients (84% and 74%, n = 62 was marginally significantly higher than the high expression patients (78.6% and 71.4%, n = 28(P = 0.0519, P = 0.0647, respectively. CONCLUSIONS: KPNA2 is

  6. Characterization of the tumor marker muc16 (ca125 expressed by murine ovarian tumor cell lines and identification of a panel of cross-reactive monoclonal antibodies

    Directory of Open Access Journals (Sweden)

    Goodell Cara AR

    2009-06-01

    Full Text Available Abstract Objectives The ovarian tumor marker CA125 is expressed on human MUC16, a cell surface bound mucin that is also shed by proteolytic cleavage. Human MUC16 is overexpressed by ovarian cancer cells. MUC16 facilitates the binding of ovarian tumor cells to mesothelial cells lining the peritoneal cavity. Additionally, MUC16 also is a potent inhibitor of natural killer cell mediated anti-tumor cytotoxic responses. Extensive studies using human as well as murine ovarian tumor cell models are required to clearly define the function of MUC16 in the progression of ovarian tumors. The major objective of this study was to determine if the murine ovarian tumor cells, MOVCAR, express Muc16 and to characterize antibodies that recognize this mucin. Methods RT-PCR analysis was used for detecting the Muc16 message and size exclusion column chromatography for isolating Muc16 produced by MOVCAR cells. Soluble and cell-associated murine Muc16 were analyzed, respectively, by Western blotting and flow cytometry assays using a new panel of antibodies. The presence of N-linked oligosaccharides on murine Muc16 was determined by ConA chromatography. Results We demonstrate that murine Muc16 is expressed by mouse ovarian cancer cells as an ~250 kDa glycoprotein that carries both O-linked and N-linked oligosaccharides. In contrast to human MUC16, the murine ortholog is primarily released from the cells and cannot be detected on the cell surface. Since the released murine Muc16 is not detected by conventional anti-CA125 assays, we have for the first time identified a panel of anti-human MUC16 antibodies that also recognizes the murine counterpart. Conclusion The antibodies identified in this study can be used in future purification of murine Muc16 and exhaustive study of its properties. Furthermore, the initial identification and characterization of murine Muc16 is a vital preliminary step in the development of effective murine models of human ovarian cancer. These

  7. DNA ploidy and S phase fraction of breast and ovarian tumor cells treated with a natural anthracycline analog (aloin).

    Science.gov (United States)

    Esmat, Amr Y; El-Gerzawy, Shadia M; Rafaat, Amira

    2005-01-01

    DNA ploidy and S phase fraction analysis by flow cytometry on breast and ovarian tumor cells continuously exposed to aloin, a natural anthraquinone, at two concentrations (20-60 microg/ml) was done. Untreated breast and ovarian tumor cells (control) showed an aneuploid pattern, with a mean DNA index of 2.10+/-0.10 and S phase fraction of 28.46+/-1.5 and 17.40+/-0.75%, respectively. Treatment of breast and ovarian tumor cells with aloin showed a persistent aneuploid pattern and a significantly dose-dependent increase in the percentage of S phase fraction and in the proportion of cells cycling at a higher ploidy level (>G2M). The polyploidization indicates that aloin does not inhibit initiation of DNA synthesis and that cells replicated a full complement of DNA but had difficulty in M phase.

  8. Distribution of Microsatellite instability in Danish ovarian tumor patients and the prognostic value in ovarian cancer patients

    DEFF Research Database (Denmark)

    Begum, F.D.; Kjaer, S.K.; Blaakaer, J.

    2008-01-01

    The repeated frequency of microsatellite instability (MSI) in ovarian cancer (OC) ranges from 0% to 50%. Most MSI studies including OC patients have involved relatively small number of tumors, a wide range of different MSI markers, different patient characteristics, and varying criteria......17S250, CACNLB1, D18S58, D19S49, DXS538, DXS454, D5S117, D5S107, D6S284, D6S305, D9S171, D9S15, D11S554, D11S29, and D13S272 in tissue from patients with OC or BOT and to correlate the presence of MSI at these markers with the clinical information, such as FIGO stage, histological type, age...... specific survival was found between stage III/IV OC patients who presented MSI compared to patients being microsatellite stable (MSS) (p = 0.72). In conclusion, we found no association to any of the clinical parameters evaluated, although a tendency of a higher frequency of MSI was observed among serous OC...

  9. Improving efficacy of metastatic tumor segmentation to facilitate early prediction of ovarian cancer patients' response to chemotherapy

    Science.gov (United States)

    Danala, Gopichandh; Wang, Yunzhi; Thai, Theresa; Gunderson, Camille C.; Moxley, Katherine M.; Moore, Kathleen; Mannel, Robert S.; Cheng, Samuel; Liu, Hong; Zheng, Bin; Qiu, Yuchen

    2017-02-01

    Accurate tumor segmentation is a critical step in the development of the computer-aided detection (CAD) based quantitative image analysis scheme for early stage prognostic evaluation of ovarian cancer patients. The purpose of this investigation is to assess the efficacy of several different methods to segment the metastatic tumors occurred in different organs of ovarian cancer patients. In this study, we developed a segmentation scheme consisting of eight different algorithms, which can be divided into three groups: 1) Region growth based methods; 2) Canny operator based methods; and 3) Partial differential equation (PDE) based methods. A number of 138 tumors acquired from 30 ovarian cancer patients were used to test the performance of these eight segmentation algorithms. The results demonstrate each of the tested tumors can be successfully segmented by at least one of the eight algorithms without the manual boundary correction. Furthermore, modified region growth, classical Canny detector, and fast marching, and threshold level set algorithms are suggested in the future development of the ovarian cancer related CAD schemes. This study may provide meaningful reference for developing novel quantitative image feature analysis scheme to more accurately predict the response of ovarian cancer patients to the chemotherapy at early stage.

  10. Peritoneal borderline cystoadenocarcinoma

    Directory of Open Access Journals (Sweden)

    Manoel João Batista Castello Girão

    Full Text Available Carcinomas of peritoneal origin represent a seldom diagnosed entity of unknown etiology, with important implications in terms of prophylactic oophorectomy. Initially described in patients belonging to families at high risk for ovarian cancer, it possibly has a pathogeny similar to that of endosalpingiosis and of some cases of endometriosis. We report a case of peritoneal borderline mucinous carcinoma with an anatomopathological diagnosis of normal ovaries.

  11. Mechanism of Ovarian Epithelial Tumor Predispostion in Individuals Carrying Germline BRCA1 Mutations

    National Research Council Canada - National Science Library

    Dubeau, Louis

    2005-01-01

    .... Given the strong link between menstrual activity and risk of ovarian cancer in the general population, we hypothesized that BRCA1 might predispose to ovarian cancer indirectly, by influencing ovarian...

  12. Mechanism of Ovarian Epithelial Tumor Predisposition in Individuals Carrying Germline BRCA1 Mutations

    National Research Council Canada - National Science Library

    Dubeau, Louis

    2006-01-01

    .... Given the strong link between menstrual activity and risk of ovarian cancer in the general population, we hypothesized that BRCA1 might predispose to ovarian cancer indirectly, by influencing ovarian...

  13. [Epidemiological profile of ovarian cancer].

    Science.gov (United States)

    Rivas-Corchado, Luz María; González-Geroniz, Manuel; Hernández-Herrera, Ricardo Jorge

    2011-09-01

    In Mexico, ovarian cancer represents 5.3% of cancer diagnoses in all age groups and 21% of gynecologic cancers. The states with the highest incidence of this disease Nuevo León, Mexico State and Federal District. To determine the epidemiological profile of ovarian cancer. A retrospective cross-sectional study that included all patients with complete records, diagnosed with ovarian cancer treated at the Oncology department UMAE Monterrey No. 23, January 2009 to 31 December 2009. We identified 40 patients with ovarian cancer. The average age of menarche was 12.7 years, 40% were of reproductive age, 25% were nulliparous, 15% had a pregnancy and 37.5% had two pregnancies. Of the total patients, 17% had a history of breast cancer, 40% used a contraceptive method, 37% used oral contraceptives. The tumor marker CA 125 was found in 40% of patients, 63.1% had ultrasound markers for cancer. The most frequent clinical stage 1A in which they found 32% of cases. Papillary serous adenocarcinoma was diagnosed in 25% of patients, endometroid adenocarcinoma and mucinous tumor of low malignant potential was diagnosed borderline at 20%, poorly differentiated adenocarcinoma in 18% tumor granulosa cells in 7% and papillary adenocarcinoma ring cell adenocarcinoma in 5%. In total, 43% of patients received chemotherapy. The majority of cases tenia50 years or more. The background was the most frequent hereditary breast cancer. There were no deaths during the study.

  14. VEGFR2-Targeted Ultrasound Imaging Agent Enhances the Detection of Ovarian Tumors at Early Stage in Laying Hens, a Preclinical Model of Spontaneous Ovarian Cancer.

    Science.gov (United States)

    Barua, Animesh; Yellapa, Aparna; Bahr, Janice M; Machado, Sergio A; Bitterman, Pincas; Basu, Sanjib; Sharma, Sameer; Abramowicz, Jacques S

    2015-07-01

    Tumor-associated neoangiogenesis (TAN) is an early event in ovarian cancer (OVCA) development. Increased expression of vascular endothelial growth factor receptor 2 (VEGFR2) by TAN vessels presents a potential target for early detection by ultrasound imaging. The goal of this study was to examine the suitability of VEGFR2-targeted ultrasound contrast agents in detecting spontaneous OVCA in laying hens. Effects of VEGFR2-targeted contrast agents in enhancing the intensity of ultrasound imaging from spontaneous ovarian tumors in hens were examined in a cross-sectional study. Enhancement in the intensity of ultrasound imaging was determined before and after injection of VEGFR2-targeted contrast agents. All ultrasound images were digitally stored and analyzed off-line. Following scanning, ovarian tissues were collected and processed for histology and detection of VEGFR2-expressing microvessels. Enhancement in visualization of ovarian morphology was detected by gray-scale imaging following injection of VEGFR2-targeted contrast agents. Compared with pre-contrast, contrast imaging enhanced the intensities of ultrasound imaging significantly (p ultrasound imaging was significantly (p ultrasound imaging in hens with OVCA were positively correlated with increased (p therapeutics. © The Author(s) 2014.

  15. Clostridium perfringens enterotoxin carboxy-terminal fragment is a novel tumor-homing peptide for human ovarian cancer

    International Nuclear Information System (INIS)

    Cocco, Emiliano; Mor, Gil; Schwartz, Peter E; Arin-Silasi, Dan; Azoudi, Masoud; Rutherford, Thomas J; Abu-Khalaf, Maysa; Pecorelli, Sergio; Santin, Alessandro D; Casagrande, Francesca; Bellone, Stefania; Richter, Christine E; Bellone, Marta; Todeschini, Paola; Holmberg, Jennie C; Fu, Han Hsuan; Montagna, Michele K

    2010-01-01

    Development of innovative, effective therapies against recurrent/chemotherapy-resistant ovarian cancer remains a high priority. Using high-throughput technologies to analyze genetic fingerprints of ovarian cancer, we have discovered extremely high expression of the genes encoding the proteins claudin-3 and claudin-4. Because claudin-3 and -4 are the epithelial receptors for Clostridium perfringens enterotoxin (CPE), and are sufficient to mediate CPE binding, in this study we evaluated the in vitro and in vivo bioactivity of the carboxy-terminal fragment of CPE (i.e., CPE 290-319 binding peptide) as a carrier for tumor imaging agents and intracellular delivery of therapeutic drugs. Claudin-3 and -4 expression was examined with rt-PCR and flow cytometry in multiple primary ovarian carcinoma cell lines. Cell binding assays were used to assess the accuracy and specificity of the CPE peptide in vitro against primary chemotherapy-resistant ovarian carcinoma cell lines. Confocal microscopy and biodistribution assays were performed to evaluate the localization and uptake of the FITC-conjugated CPE peptide in established tumor tissue. Using a FITC-conjugated CPE peptide we show specific in vitro and in vivo binding to multiple primary chemotherapy resistant ovarian cancer cell lines. Bio-distribution studies in SCID mice harboring clinically relevant animal models of chemotherapy resistant ovarian carcinoma showed higher uptake of the peptide in tumor cells than in normal organs. Imunofluorescence was detectable within discrete accumulations (i.e., tumor spheroids) or even single chemotherapy resistant ovarian cancer cells floating in the ascites of xenografted animals while a time-dependent internalization of the FITC-conjugated CPE peptide was consistently noted in chemotherapy-resistant ovarian tumor cells by confocal microscopy. Based on the high levels of claudin-3 and -4 expression in chemotherapy-resistant ovarian cancer and other highly aggressive human epithelial

  16. Advances in Tumor Screening, Imaging, and Avatar Technologies for High-Grade Serous Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Anders eOhman

    2014-11-01

    Full Text Available The majority of high-grade serous ovarian carcinoma cases are detected in advanced stages when treatment options are limited. Surgery is less effective at eradicating the disease when it is widespread, resulting in high rates of disease relapse and chemoresistance. Current screening techniques are ineffective for early tumor detection and consequently, BRCA mutations carriers, with an increased risk for developing high-grade serous ovarian cancer, elect to undergo risk-reducing surgery. While prophylactic surgery is associated with a significant reduction in the risk of cancer development, it also results in surgical menopause and significant adverse side effects. The development of efficient early-stage screening protocols and imaging technologies is critical to improving the outcome and quality of life for current patients and women at increased risk. In addition, more accurate animal models are necessary in order to provide relevant in vivo testing systems and advance our understanding of the disease origin and progression. Moreover, both genetically engineered and tumor xenograft animal models enable the preclinical testing of novel imaging techniques and molecularly targeted therapies as they become available. Recent advances in xenograft technologies have made possible the creation of avatar mice, personalized tumorgrafts, which can be used as therapy testing surrogates for individual patients prior to or during treatment. High-grade serous ovarian cancer may be an ideal candidate for use with avatar models based on key characteristics of the tumorgraft platform. This review explores multiple strategies, including novel imaging and screening technologies in both patients and animal models, aimed at detecting cancer in the early stages and improving the disease prognosis.

  17. Prognostic Significance of the Tumor-Stroma Ratio in Epithelial Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Ying Chen

    2015-01-01

    Full Text Available Tumor-stroma ratio (TSR has recently been identified as a promising prognostic parameter for several solid tumors. This study aimed to evaluate the prognostic role of TSR in epithelial ovarian cancer (EOC and 838 EOC patients were enrolled in this study. TSR was estimated on hematoxylin-and-eosin-stained tissue sections from the most invasive part of the primary tumor. Patients were classified as stroma-rich or stroma-poor according to the proportion of stroma ≥50% or <50%. Chi-square test analysis revealed that TSR were significantly associated with FIGO stage, LN status, and recurrence or not (all of them P<0.001. The higher stroma-rich proportions were found in EOC patients with advanced stage (36.13% versus 19.75%, LN metastasis (51.93% versus 27.25%, and recurrence (34.27% versus 6.82%. Stroma-rich EOC patients had obvious shorter median time of progression-free survival (29 versus 39 months and overall survival (50 versus 58 months, respectively. TSR was an independent prognostic factor for the evaluation of PFS in EOC. Stroma-rich tumors had worse prognosis and higher risk of relapse compared with those in stroma-poor tumors in EOC patients. Considered easy to determine for routine pathological examination, TSR may serve as a new prognostic histological parameter in EOC.

  18. Ovarian tumor characterization and classification: a class of GyneScan™ systems.

    Science.gov (United States)

    Acharya, U Rajendra; Sree, Vinitha S; Saba, Luca; Molinari, Filippo; Guerriero, Stefano; Suri, Jasjit S

    2012-01-01

    In this work, we have developed an adjunct Computer Aided Diagnostic (CAD) technique that uses 3D acquired ultrasound images of the ovary and data mining algorithms to accurately characterize and classify benign and malignant ovarian tumors. In this technique, we extracted image-texture based and Higher Order Spectra (HOS) based features from the images. The significant features were then selected and used to train and test the Decision Tree (DT) classifier. The proposed technique was validated using 1000 benign and 1000 malignant images, obtained from 10 patients with benign and 10 with malignant disease, respectively. On evaluating the classifier with 10-fold stratified cross validation, we observed that the DT classifier presented a high accuracy of 95.1%, sensitivity of 92.5% and specificity of 97.7%. Thus, the four significant features could adequately quantify the subtle changes and nonlinearities in the pixel intensities. The preliminary results presented in this paper indicate that the proposed technique can be reliably used as an adjunct tool for ovarian tumor classification since the system is accurate, completely automated, cost-effective, and can be easily written as a software application for use in any computer.

  19. [The assessment of the dependence between antigen CA 125 and nicotinism in patients with benign ovarian tumors including endometrial cysts].

    Science.gov (United States)

    Posadzka, Ewa; Jach, Robert; Babczyk, Dorota; Knafel, Anna; Pityński, Kazimierz

    2014-01-01

    Cancer antigen CA-125 is a marker that is primarily used to differentiate benign from malignant tumors as well as to monitor response to ovarian cancer treatment. Taken as a separate marker, it displays low sensitivity and specificity in ovarian cancer diagnosis; however, in combination with other markers it may be successfully applied especially in postmenopausal women. Elevated CA-125 levels in blood serum indicate cancerous as well as non-cancerous diseases. Research aiming to determine environmental factors that may have influence on antigen CA-125 level, and thus on the assessment of this marker's application in gynecological and oncological diseases continues. the aim of the present research is an attempt to estimate the influence of nicotinism on antigen CA-125 in blood serum in patients with diagnosed benign ovarian tumors including endometrial cysts. 174 women aged 16-85 years with diagnosed benign ovarian tumor were qualified for the study. In all patients level of antigen CA-125 in blood serum was assessed preoperatively and nicotinism history was taken. Also transvaginal ultrasound was performed to obtain preliminary diagnosis. Smoking and non-smoking patients were classified into two groups, namely of those with histopathologically confirmed cysts of endometrial type and those with non-endometrial benign ovarian tumors. statistical analysis did not prove any dependence between the CS-125 antigen level and nicotinism in any of these groups. Also additional analysis with division into premenopausal and postmenopausal patients did not determine any statistically significant dependence. Nicotinism does not significantly influence the CA-125 antigen level in patients with benign However, the connection between the addiction severity and its influence on antigen CA-125 in blood serum cannot be excluded. ovarian tumors or endometrial cysts.

  20. Ovarian Sertoli-Leydig Cell Tumor with Elevated Inhibin B as a Cause of Secondary Amenorrhea in an Adolescent with Germ Line DICER1 Mutation.

    Science.gov (United States)

    Luke, Amy M; Moroney, John W; Snitchler, Andrea; Whiteway, Susan L

    2017-10-01

    Ovarian tumors, although uncommon in children, can retain endocrine function that disrupts normal feedback mechanisms leading to amenorrhea. Inheritance of germline DICER1 mutations can lead to increased risk for development of ovarian Sertoli-Leydig cell tumors (SLCTs). We report, to our knowledge, the first case of secondary amenorrhea due to elevated inhibin B levels in a female adolescent with an ovarian SLCT. Ovarian tumors should be included in the differential diagnosis for pediatric patients who present with menstrual irregularities. Early evaluation of the hypothalamic-pituitary-ovarian axis and inhibin levels is appropriate. Our case also emphasizes the need for testing for DICER1 mutations in pediatric patients with ovarian SLCTs. Published by Elsevier Inc.

  1. Characterization of the Chicken Ovarian Cancer Model

    National Research Council Canada - National Science Library

    Rodriquez, Gustavo

    2001-01-01

    .... Unlike other ovarian cancer models, which require experimental induction of ovarian tumors, chickens develop ovarian adenocarcinoma spontaneously, with an incidence ranging from 13 to 40 percent...

  2. Characterization of the Chicken Ovarian Cancer Model

    National Research Council Canada - National Science Library

    Rodriguez, Gustavo C

    2004-01-01

    .... Unlike other ovarian cancer models, which require experimental induction of ovarian tumors, chickens develop ovarian adenocarcinoma spontaneously, with an incidence ranging from 13 to 40 percent...

  3. Characterization of the Chicken Ovarian Cancer Model

    National Research Council Canada - National Science Library

    Rodriguez, Gustavo

    2002-01-01

    .... Unlike other ovarian cancer models, which require experimental induction of ovarian tumors, chickens develop ovarian adenocarcinoma spontaneously, with an incidence ranging from 13 to 40 percent...

  4. Characterization of the Chicken Ovarian Cancer Model

    National Research Council Canada - National Science Library

    Rodriguez, Gustavo C

    2005-01-01

    .... Unlike other ovarian cancer models, which require experimental induction of ovarian tumors, chickens develop ovarian adenocarcinoma spontaneously, with an incidence ranging from 13 to 40 percent...

  5. Characterization of the Chicken Ovarian Cancer Model

    National Research Council Canada - National Science Library

    Rodriguez, Gustavo

    2003-01-01

    .... Unlike other ovarian cancer models, which require experimental induction of ovarian tumors, chickens develop ovarian adenocarcinoma spontaneously, with an incidence ranging from 13 to 40 percent...

  6. Development of a double-antibody radioimmunoassay for detecting ovarian tumor-associated antigen fraction OCA in plasma

    International Nuclear Information System (INIS)

    Knauf, S.; Urbach, G.I.

    1978-01-01

    Ovarian tumor-associated antigen isolated from human tumor tissue was shown to have a different mobility from that of carcinoembryonic antigen (CEA) in both acrylamide gel electrophoresis and immunoelectrophoresis in agarose. The ovarian tumor antigen is composed of six species with different electrophoretic mobility in acrylamide gel electrophoresis. Three of these species were detected in Sephadex G-100 ovarian fraction OCA (from the void volume peak) and the other three species of lower apparent molecular weight were detected in fraction OCD (from the second peak). Fractions OCA and OCD did not share common antigenic determinants as determined by immunodiffusion. CEA was shown to share antigenic determinants with both OCA and OCD. A double-antibody radioimmunoassay capable of detecting nanogram quantities of plasma OCA was developed. In a preliminary study of ovarian cancer patients, OCA appeared to be a more sensitive marker for ovarian cancer than CEA. There was virtually no correlation (r 2 = 0.1) between OCA and CEA levels in these patients, as determined by radioimmunoassay

  7. TLR4 activates NF-{kappa}B in human ovarian granulosa tumor cells

    Energy Technology Data Exchange (ETDEWEB)

    Woods, Dori C., E-mail: dwoods2@partners.org [Vincent Center for Reproductive Biology, Vincent Obstetrics and Gynecology Service, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02114 (United States); White, Yvonne A.R. [Vincent Center for Reproductive Biology, Vincent Obstetrics and Gynecology Service, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02114 (United States); Dau, Caroline [University of California, San Francisco, School of Dentistry, San Francisco, CA 94143 (United States); Johnson, A.L. [Center for Reproductive Biology and Health, The Pennsylvania State University, University Park, PA 16802 (United States)

    2011-06-17

    Highlights: {yields} TLR4 is expressed in human ovarian granulosa tumor cells. {yields} Acting through TLR4, LPS and HSP60 induce a NF{kappa}B signaling cascade in human ovarian granulosa tumor cells. {yields} NF{kappa}B activation or inhibition did not alter chemosensitivity to TRAIL or cisplatin. -- Abstract: Previous studies have demonstrated expression of Toll-like receptors (TLRs) in the surface epithelium of normal ovaries (OSE) and in epithelial ovarian tumors. Most notably, OSE-derived cancers express TLR4, which activates the nuclear factor-kappa B (NF-{kappa}B) signaling cascade as a mediator of inflammatory response. Currently, there is considerable interest in elucidating the role of TLR-mediated signaling in cancers. Nevertheless, the expression of TLRs in granulosa cell tumors (GCTs) of the ovary, and the extent to which GCT expression of TLRs may influence cell-signaling pathways and/or modulate the efficacy of chemotherapeutics, has yet to be determined. In the present study, human GCT lines (COV434 and KGN) were utilized to evaluate expression of functional TLR4. TLR4 is expressed in GCT cell lines and ligation of TLR4 with bacterial lipopolysaccharide (LPS) led to I{kappa}B degradation and activation of NF-{kappa}B. NF-{kappa}B activation was confirmed by nuclear localization of NF-{kappa}B p65 following treatment with LPS and the naturally occurring ligand, HSP60. Notably, immunoneutralization of TLR4 blocked nuclear localization, and inhibition of NF-{kappa}B signaling attenuated LPS-induced TNF{alpha} plus increased doubling time in both cell lines. Contradictory to reports using human OSE cell lines, inhibition of NF-{kappa}B signaling failed to sensitize GCT lines to TRAIL or cisplatin. In summary, findings herein are the first to demonstrate a functional TLR-signaling pathway specifically in GCTs, and indicate that in contrast to OSE-derived cancers, inhibition of NF-{kappa}B does not sensitize GCTs to TRAIL or cisplatin.

  8. Significance of the tumor markers CA 125 and CA 15-3 in postoperative diagnosis of ovarian and breast cancer

    International Nuclear Information System (INIS)

    Johannsen, B.; Bartel, U.; Elling, D.

    1989-01-01

    In 271 patients with ovarian carcinoma, benign ovarian tumors, breast cancer, and two control groups, serum levels of CA 125, CA 15-3, CEA and, partly, CA 19-9 were determined immunoradiometrically. According to the results of the determination of CA 125 in the follow-up of ovarian carcinoma, CA 125 represents a useful marker for early detection of recurrences, especially in cases of diffuse carcinoma dissemination. In incomplete tumor debulking, postoperative CA 125 serum levels did not prove to be helpful except that a positive level renders invasive diagnostic investigation no longer necessary. Postoperative follow-up in breast cancer early reveals distant metastases, with very high levels in patients with bone metastases. By simultaneous measurement of CA 15-3 and CEA the sensitivity could be increased from 86% (CA 15-3 only) to 93%. (author)

  9. [Expressions of Ras and Sos1 in epithelial ovarian cancer tissues and their clinical significance].

    Science.gov (United States)

    Xiao, Zheng-Hua; Linghu, Hua; Liu, Qian-Fen

    2016-11-20

    To detect the expressions of Ras and Sos1 proteins in human epithelial ovarian cancer (EOC) tissues and explore their correlation with the clinicopathological features of the patients. The expressions of Ras and Sos1 proteins were detected immunohistochemically in 62 EOC tissues, 5 borderline ovarian cancer tissues, 15 benign epithelial ovarian neoplasm tissues, and 18 normal ovarian tissues. The EOC tissues showed significantly higher expression levels of both Ras and Sos1 than the other tissues tested (Ptissues, Ras and Sos1 proteins were expressed mostly on the cell membrane and in the cytoplasm. The expression level of Ras was correlated with pathological types of the tumor (Ptissue-specific variation of Ras expression can lend support to a specific diagnosis of ovarian serous adenocarcinoma. The association of Ras and Sos1 protein expression with the tumor-free survival time of the patients awaits further investigation with a larger sample size.

  10. Small putative NANOG, SOX2, and SSEA-4-positive stem cells resembling very small embryonic-like stem cells in sections of ovarian tissue in patients with ovarian cancer.

    Science.gov (United States)

    Virant-Klun, Irma; Kenda-Suster, Natasa; Smrkolj, Spela

    2016-03-03

    In previous studies it has been found that in cell cultures of human adult ovaries there is a population of small stem cells with diameters of 2-4 μm, which are present mainly in the ovarian surface epithelium and are comparable to very small embryonic-like stem cells (VSELs) from bone marrow. These cells are not observed by histopathologists in the ovarian tissue due to their small size and unknown clinical significance. Because these cells express a degree of pluripotency, they might be involved in the manifestation of ovarian cancer. Therefore we studied the ovarian tissue sections in women with borderline ovarian cancer and serous ovarian carcinoma to perhaps identify the small putative stem cells in situ. In 27 women with borderline ovarian cancer and 20 women with high-grade serous ovarian carcinoma the ovarian tissue sections were stained, per standard practice, with eosin and hematoxylin staining and on NANOG, SSEA-4 and SOX2 markers, related to pluripotency, using immunohistochemistry. We focused on the presence and localization of small putative stem cells with diameters of up to 5 μm and with the nuclei spread over nearly the full cell volume. In ovarian sections of both borderline ovarian cancer and serous ovarian carcinoma patients we were able to identify the presence of small round cells complying with the above criteria. Some of these small cells were NANOG-positive, were located among epithelial cells in the ovarian surface epithelium and as a single cell or groups of cells/clusters in typical "chambers", were found only in the presence of ovarian cancer and not in healthy ovaries and are comparable to those in fetal ovaries. We envision that these small cells could be related to NANOG-positive tumor-like structures and oocyte-like cells in similar "chambers" found in sections of cancerous ovaries, which could support their stemness and pluripotency. Further immunohistochemistry revealed a similar population of SSEA-4 and SOX2-positive cells. We

  11. Evaluation of 99mTc-Labeled Bevacizumab-N-HYNIC Conjugate in Human Ovarian Tumor Xenografts.

    Science.gov (United States)

    Shah, Syed Qaiser; Mahmood, Samia

    2018-03-20

    The aim of the present investigation was to examine the suitability of 99m Tc-N-HYNIC-BZMB as a specific vascular endothelial growth factor (VEGF)-targeting agent. Bevacizumab is a recombinant humanized monoclonal antibody that inhibits VEGF. N-hydroxysuccinimide-2-hydrazinonicotinic acid (N-HYNIC) was conjugated to BZMB, followed by labeling with 99m Tc using N-[Tris(hydroxymethyl)methyl] glycine (tricine), ethylenediamine-N,N'-diacetic acid (EDDA), and nicotinic acid as coligands. 99m Tc-labeled BZMB was characterized in terms of 99m TcO 4 , radiocolloids, and labeled N-HYNIC-BZMB using thin-layer chromatography and HPLC. Poor metastatic SKOV-3 and high metastatic SKOV-3.ip1 human ovarian cancer cell lines were used for in vitro binding uptake of 99m Tc-N-HYNIC-BZMB. Biodistribution and scintigraphy accuracy were examined in human ovarian tumor xenografts in rats and rabbits. 99m Tc-N-HYNIC-BZMB prepared by using a mixture of tricine and EDDA demonstrated relatively high radiochemical purity (more than 98%). In L-cysteine and serum, it exhibited a stable behavior up to 16 hours. In vitro binding uptake indicated that it targets high metastatic SKOV-3.ip1 tumors. Biodistribution in human ovarian tumor xenografts in rats confirmed a significant uptake in SKOV-3.ip1 tumors (5.69% ± 1.86%, 4 hours). Scintigraphic accuracy in human ovarian tumor xenografts in rabbits validated its suitability as a high metastatic SKOV-3.ip1 radiotracer. High radiochemical purity, stability in saline and serum, biodistribution, and scintigraphy of 99m Tc-N-HYNIC-BZMB in human ovarian tumor xenografts in rats and rabbits confirmed its suitability as a potential radiotracer for imaging high metastatic SKOV-3.ip1 sites.

  12. RhoC is a major target of microRNA-93-5P in epithelial ovarian carcinoma tumorigenesis and progression.

    Science.gov (United States)

    Chen, Xi; Chen, Shuo; Xiu, Yin-Ling; Sun, Kai-Xuan; Zong, Zhi-Hong; Zhao, Yang

    2015-02-04

    An increasing amount of evidence has revealed that microRNAs regulate various biological processes, including cell differentiation, cell proliferation, apoptosis, drug resistance, and fat metabolism. Studies have shown that miR-93's targetome in cancer has not been fully defined. Moreover, the role of miR-93 in epithelial ovarian carcinoma (EOC) remains largely unknown. MIR-93 mRNA expression in normal ovarian tissue, benign tumors, borderline tumors, primary ovarian carcinomas, and metastatic omentum was quantified. The ovarian carcinoma cell lines OVCAR3, SKOV3/DDP, and HO8910-PM were transfected with miR-93-5P, after which cell phenotype and expression of relevant molecules were assayed. Dual-luciferase reporter assay and a xenograft mouse model were used to examine miR-93 and its target gene RHOC (Ras homolog gene family member C). MIR-93 mRNA expression was significantly lower in ovarian carcinomas and borderline tumors than in normal ovarian tissues (p ovarian carcinomas (p ovarian carcinoma (p ovarian cellular proliferation. The involvement of miR-93-5P-mediated RhoC downregulation in inhibiting EOC aggressiveness may provide extended insight into the molecular mechanisms underlying cancer aggressiveness.

  13. Ovarian sertoli-leydig cell tumors: A multicenter long-term clinicopathological analysis of 27 patients.

    Science.gov (United States)

    Akman, Levent; Ertas, Ibrahim Egemen; Gokcu, Mehmet; Terek, Mustafa Cosan; Sanci, Muzaffer; Sanli, Ulus Ali; Zekioglu, Osman; Ozsaran, Ahmet Aydin

    2016-01-01

    Information on the clinical behavior of ovarian Sertoli-Leydig cell tumors (SLCTs) as well as its prognostic factors and optimal management is limited due to a substantially low incidence of the disease. Also, limited data is available regarding the role of chemotherapy in the management of SLCTs. The aim of the study is to evaluate clinicopathological features and outcome of patients with ovarian SLCTs. Twenty-seven patients with SLCT treated at two centers were reviewed retrospectively during 21 years. The median age was 45 years (range, 16-81) and the mean follow-up time was 86 months (range, 16-181). Twenty-three patients had stage IA, three patients had IC, and one patient had stage II disease. Eleven tumors (41%) were well-differentiated and 16 (59%) tumors were intermediately differentiated. Nine patients underwent unilateral salpino-oophorectomy and one patient, with a history of infertility, underwent cystectomy for fertility preservation. Eight patients with intermediately differentiated types of SLCT received adjuvant systemic chemotherapy including the combination bleomycin, etoposide, and cisplatin (BEP). Recurrence occurred in one patient with intermediated differentiated type SLCT with heterologous elements. She received four cycles of BEP chemotherapy. Twelve months later, she underwent cytoreductive surgery and received six cycles of cisplatin plus carboplatin. She died 24 months after the initial diagnosis. SLCTs of the ovary are usually in early stage, unilateral, and benign. Fertility-sparing surgery is the preferred option in young women. In the adjuvant treatment setting, although information about chemotherapy is limited, BEP is a commonly used regimen. The degree of differentiation and the presence of heterologous elements relate to a poor prognosis.

  14. Mutation of NRAS is a Rare Genetic Event in Ovarian Low-Grade Serous Carcinoma

    DEFF Research Database (Denmark)

    Xing, Deyin; Rahmanto, Yohan Suryo; Zeppernick, Felix

    2017-01-01

    Activating mutations involving the members of the RAS signaling pathway, including KRAS, NRAS, and BRAF, have been reported in ovarian low-grade serous carcinoma and its precursor lesion, serous borderline tumor (SBT). Whether additional genetic alterations in the RAS oncogene family accumulate...... during the progression of serous borderline tumor (SBT) to invasive low grade serous carcinoma (LGSC) remains largely unknown. While mutations of KRAS and BRAF occur at a very early stage of progression, even preceding the development of SBT, additional driving events, such as NRAS mutations, have been...

  15. Accuracy of intraoperative frozen section for the evaluation of ovarian neoplasms: an institutional experience.

    Science.gov (United States)

    Hashmi, Atif Ali; Naz, Samreen; Edhi, Muhammad Muzzammil; Faridi, Naveen; Hussain, Syed Danish; Mumtaz, Shazia; Khan, Mehmood

    2016-03-31

    Ovarian neoplasms are a heterogeneous group of tumors including surface epithelial, germ cell and sex cord stromal tumors with a subset having low malignant potential (borderline tumors). While the surgical management plan differs in different categories of tumors, preoperative diagnosis is seldom available. In these circumstances, the role of frozen section becomes invaluable. In the current study, we aimed to evaluate the accuracy of the frozen section of ovarian tumors in our setup. It was a retrospective study involving 141 cases of ovarian tumors undergoing surgical resection with frozen section evaluation from January 2009 to December 2014. After gross examination, one to five blocks were prepared on the frozen section depending upon the size of the specimen. After frozen section reporting, specimens were processed routinely for final paraffin section evaluation. Results of frozen and paraffin sections were categorized in benign, borderline, and malignant, and accuracy of frozen section was determined. Out of 141 cases, 107 were diagnosed as benign on final (paraffin) examination, while 6 were borderline and 28 were malignant. Out of 107 benign cases, 45 were non-neoplastic cystic lesions of the ovary including endometriotic, follicular, and corpus luteal cysts. The most common benign neoplastic tumor was mature cystic teratoma (20 cases) followed by mucinous cystadenoma (19 cases), serous cystadenoma (14 cases), sex cord stromal tumors (8 cases), and Brenner tumor (1 case). Among borderline cases, four cases were serous and two of mucinous neoplasms. The most common malignant neoplasm was serous carcinoma (11 cases) followed by mucinous carcinoma (6 cases). The overall accuracy of frozen section diagnosis is above 99 %. The sensitivity and specificity for benign tumors were found to be 100 and 97 %, respectively. The sensitivity and specificity for borderline tumors was 83 and 99 %, respectively, while for malignant tumors, it was 96 and 100

  16. Using literature and data to learn Bayesian networks as clinical models of ovarian tumors.

    Science.gov (United States)

    Antal, Peter; Fannes, Geert; Timmerman, Dirk; Moreau, Yves; De Moor, Bart

    2004-03-01

    Thanks to its increasing availability, electronic literature has become a potential source of information for the development of complex Bayesian networks (BN), when human expertise is missing or data is scarce or contains much noise. This opportunity raises the question of how to integrate information from free-text resources with statistical data in learning Bayesian networks. Firstly, we report on the collection of prior information resources in the ovarian cancer domain, which includes "kernel" annotations of the domain variables. We introduce methods based on the annotations and literature to derive informative pairwise dependency measures, which are derived from the statistical cooccurrence of the names of the variables, from the similarity of the "kernel" descriptions of the variables and from a combined method. We perform wide-scale evaluation of these text-based dependency scores against an expert reference and against data scores (the mutual information (MI) and a Bayesian score). Next, we transform the text-based dependency measures into informative text-based priors for Bayesian network structures. Finally, we report the benefit of such informative text-based priors on the performance of a Bayesian network for the classification of ovarian tumors from clinical data.

  17. Cyclin D1 Expression and the Inhibitory Effect of Celecoxib on Ovarian Tumor Growth in Vivo

    Directory of Open Access Journals (Sweden)

    Ling-Yun Zhai

    2010-10-01

    Full Text Available The report aims to investigate the relationship between the expression of cyclin D1 and Cyclooxgenase-2 (COX-2, thus to explore the molecular mechanisms of the antitumor efficacy of Celecoxib, a COX-2 inhibitor. Human ovarian SKOV-3 carcinoma cell xenograft-bearing mice were treated with Celecoxib by infusing gaster (i.g. twice/day for 21 days. The mRNA levels of COX-2 and cyclin D1 were determined by RT-PCR. The expression of cyclin D1 at the protein level was detected by immunohistochemistry, while COX-2 protein expression was determined by Western blot. A high-dose of Celecoxib (100 mg/kg significantly inhibited tumor growth (P < 0.05, and the expression of cyclin D1 was reduced by 61%. Celecoxib decreased the proliferation cell index by 40% (P < 0.001 and increased apoptotic index by 52% (P < 0.05 in high-dose Celecoxib treated group. Our results suggest that the antitumor efficacy of Celecoxib against ovarian cancer in mice may in part be mediated through suppression of cyclin D1, which may contribute to its ability to suppress proliferation.

  18. Dietary supplementation of Ashwagandha (Withania somnifera, Dunal) enhances NK cell function in ovarian tumors in the laying hen model of spontaneous ovarian cancer.

    Science.gov (United States)

    Barua, Animesh; Bradaric, Michael J; Bitterman, Pincas; Abramowicz, Jacques S; Sharma, Sameer; Basu, Sanjib; Lopez, Heather; Bahr, Janice M

    2013-12-01

    Ovarian cancer (OVCA) disseminates in a distinct pattern through peritoneal metastasis and little is known about the immunosuppression in the tumor microenvironment. Our goal was to determine changes in NK cell population during OVCA development and the effects of Ashwagandha (Withania somnifera, Dunal) supplementation on NK cell localization in laying hens with OVCA. Frequency of NK cells in ovarian tumors at early and late stages in 3- to 4-year-old hens (exploratory study) as well as in hens supplemented with dietary Ashwagandha root powder for 90 days (prospective study) was examined. The population of stromal NK cells but not the intratumoral NK cells increased with OVCA development and progression. Ashwagandha supplementation decreased the incidence and progression of OVCA. Both the stromal and intratumoral NK cell population increased significantly (P < 0.0001) in Ashwagandha supplementated hens. The results of this study suggest that the population of stromal and tumorinfiltrating NK cells is increased by dietary Ashwagandha supplementation. Thus, Ashwagandha may enhance antitumor function of NK cells. This study may be useful for a clinical study to determine the effects of dietary Ashwagandha on NK cell immune function in patients with ovarian cancer. © 2013 John Wiley & Sons Ltd.

  19. A designed inhibitor of p53 aggregation rescues p53 tumor-suppression in ovarian carcinomas

    Science.gov (United States)

    Soragni, Alice; Janzen, Deanna M.; Johnson, Lisa M.; Lindgren, Anne G.; Nguyen, Anh Thai-Quynh; Tiourin, Ekaterina; Soriaga, Angela B.; Lu, Jing; Jiang, Lin; Faull, Kym F.; Pellegrini, Matteo; Memarzadeh, Sanaz; Eisenberg, David S.

    2015-01-01

    SUMMARY Half of all human cancers lose p53 function by missense mutations, with an unknown fraction of these containing p53 in a self-aggregated, amyloid-like state. Here we show that a cell-penetrating peptide, ReACp53, designed to inhibit p53 amyloid formation, rescues p53 function in cancer cell lines and in organoids derived from high-grade serous ovarian carcinomas (HGSOC), an aggressive cancer characterized by ubiquitous p53 mutations. Rescued p53 behaves similarly to its wild-type counterpart in regulating target genes, reducing cell proliferation and increasing cell death. Intraperitoneal administration decreases tumor proliferation and shrinks xenografts in vivo. Our data show the effectiveness of targeting a specific aggregation defect of p53 and its potential applicability to HGSOCs. PMID:26748848

  20. Serum tumor marker CA 125 for monitoring ovarian cancer during follow-up

    DEFF Research Database (Denmark)

    Tuxen, Malgorzata K.; Sölétormos, G; Dombernowsky, P

    2002-01-01

    , and the cut-off value. Additionally, the utility of a new assessment criterion based upon an increment of 2.5 times the baseline CA 125 concentration confirmed by a third measurement was investigated. The efficiency of CA 125 to identify progression and non-progression during follow-up varied between 76.......5 and 79.9%, depending on the applied time limit for an acceptable positive lead time. The median lead time for true positive results was 95-99.5 days. Using the new elaborated criterion, the efficiency of CA 125 for identifying progression and non-progression varied between 75.7 and 78.5%, depending...... utility of serological tumor markers in patients with ovarian cancer....

  1. Imaging of Tumor-Associated Macrophages in a Transgenic Mouse Model of Orthotopic Ovarian Cancer.

    Science.gov (United States)

    He, Huanhuan; Chiu, Alan C; Kanada, Masamitsu; Schaar, Bruce T; Krishnan, Venkatesh; Contag, Christopher H; Dorigo, Oliver

    2017-10-01

    Tumor-associated macrophages (TAMs) are often associated with a poor prognosis in cancer. To gain a better understanding of cellular recruitment and dynamics of TAM biology during cancer progression, we established a novel transgenic mouse model for in vivo imaging of luciferase-expressing macrophages. B6.129P2-Lyz2 tm1(cre)Ifo /J mice, which express Cre recombinase under the control of the lysozyme M promoter (LysM) were crossed to Cre-lox Luc reporter mice (RLG), to produce LysM-LG mice whose macrophages express luciferase. Cell-type-specific luciferase expression in these mice was verified by flow cytometry, and via in vivo bioluminescence imaging under conditions where macrophages were either stimulated with lipopolysaccharide or depleted with clodronate liposomes. The distribution of activated macrophages was longitudinally imaged in two immunocompetent LysM-LG mouse models with either B16 melanoma or ID8 ovarian cancer cells. In vivo imaging of LysM-LG mice showed luciferase activity was generated by macrophages. Clodronate liposome-mediated depletion of macrophages lowered overall bioluminescence while lipopolysaccharide injection increased macrophage bioluminescence in both the B16 and ID8 models. Tracking macrophages weekly in tumor-bearing animals after intraperitoneal (i.p.) or intraovarian (i.o.) injection resulted in distinct, dynamic patterns of macrophage activity. Animals with metastatic ovarian cancer after i.p. injection exhibited significantly higher peritoneal macrophage activity compared to animals after i.o. injection. The LysM-LG model allows tracking of macrophage recruitment and activation during disease initiation and progression in a noninvasive manner. This model provides a tool to visualize and monitor the benefit of pharmacological interventions targeting macrophages in preclinical models.

  2. Malignant and borderline phyllodes tumor of breast treated with a multi-modality approach in a tertiary cancer care centre in North India

    Directory of Open Access Journals (Sweden)

    Supriya Mallick

    2016-01-01

    Full Text Available Background: Phyllodes tumor (PT of the breast can be categorized into benign, borderline and malignant subgroups depending on various histopathological factors. Although malignant PTs may be indolent and controlled by local excision, they frequently show local and distant relapses. Literature reveals local recurrence to be the predominant pattern of failure and thus emphasizes the importance of adjuvant radiation in these tumors. The role of systemic chemotherapy has remained doubtful. Materials and Methods: We have analyzed details of all patients of PT (n = 33 treated with adjuvant multi-modality approach in our institute since 1994–2009. The demographic data, treatment details, recurrence patterns and salvage treatment options were documented. Results: All patients received adjuvant radiation. Seven patients received adjuvant chemotherapy. The mean survival of the entire cohort was 150.618 months. There was a trend for better overall survival with borderline grade (193.6 vs. 160.2 months; P = 0.08, log rank. The disease free survival (DFS favored borderline grade (193.6 months vs. 82.9 months for high grade; P = 0.02, log rank. The DFS was significantly better in tumors having negative margins on postoperative histopathological examination (DFS rate at 5 years being 100% vs. 69.2% for positive or close margins; P = 0.015. The mode of surgery did not have any impact on survival. Conclusion: Adjuvant Radiation should be discussed taking into account surgical margins, size and various pathological factors of the primary. Adjuvant radiation may be utilized in high risk patients to enhance loco-regional control. Systemic chemotherapy is an option, worth exploring, in cases of systemic failure.

  3. Poorly Differentiated Ovarian Sertoli-Leydig Cell Tumor in a 16-Year-Old Single Woman: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Ahmed Abu-Zaid

    2013-01-01

    Full Text Available Sertoli-Leydig cell tumor (SLCT of ovary is an exceedingly unusual neoplasm that belongs to a group of sex cord-stromal tumors of ovary and accounts for less than 0.5% of all primary ovarian neoplasms. Very few case reports have been documented in the literature so far. Herein, we report a case of primary poorly differentiated ovarian Sertoli-Leydig cell tumor (SLCT involving the left ovary in a 16-year-old single woman who presented with a 3-month history of a pelviabdominal mass, acne, hirsutism, and menstrual irregularities. In addition, a literature review on ovarian SLCTs is provided.

  4. Tumor suppressor KAI1 affects integrin αvβ3-mediated ovarian cancer cell adhesion, motility, and proliferation

    International Nuclear Information System (INIS)

    Ruseva, Zlatna; Geiger, Pamina Xenia Charlotte; Hutzler, Peter; Kotzsch, Matthias; Luber, Birgit; Schmitt, Manfred; Gross, Eva; Reuning, Ute

    2009-01-01

    The tetraspanin KAI1 had been described as a metastasis suppressor in many different cancer types, a function for which associations of KAI1 with adhesion and signaling receptors of the integrin superfamily likely play a role. In ovarian cancer, integrin αvβ3 correlates with tumor progression and its elevation in vitro provoked enhanced cell adhesion accompanied by significant increases in cell motility and proliferation in the presence of its major ligand vitronectin. In the present study, we characterized integrin αvβ3-mediated tumor biological effects as a function of cellular KAI1 restoration and proved for the first time that KAI1, besides its already known physical crosstalk with β1-integrins, also colocalizes with integrin αvβ3. Functionally, elevated KAI1 levels drastically increased integrin αvβ3/vitronectin-dependent ovarian cancer cell adhesion. Since an intermediate level of cell adhesive strength is required for optimal cell migration, we next studied ovarian cancer cell motility as a function of KAI1 restoration. By time lapse video microscopy, we found impaired integrin αvβ3/vitronectin-mediated cell migration most probably due to strongly enhanced cellular immobilization onto the adhesion-supporting matrix. Moreover, KAI1 reexpression significantly diminished cell proliferation. These data strongly indicate that KAI1 may suppress ovarian cancer progression by inhibiting integrin αvβ3/vitronectin-provoked tumor cell motility and proliferation as important hallmarks of the oncogenic process.

  5. A novel DICER1 mutation identified in a female with ovarian Sertoli-Leydig cell tumor and multinodular goiter

    DEFF Research Database (Denmark)

    Rossing, Maria; Gerdes, Anne-Marie; Juul, Anders

    2014-01-01

    ) of Danish ethnicity presented with both an ovarian Sertoli-Leydig cell tumor and a multinodular goiter at the age of 13 years. In addition, family history included a male sibling (case 2 patient) who also had a multinodular goiter and had undergone a hemithyroidectomy at the age of 14 years. Subsequent......INTRODUCTION: Germ-line mutations in the micro-ribonucleic acid processing gene DICER1 have been shown to predispose to a subset of benign tumors susceptible to malignant transformation, including ovarian Sertoli-Leydig cell tumor, nontoxic multinodular goiter, multilocular cystic nephroma...... and pleuropulmonary blastoma, which can occur in children and young adults. This may be due to reduced Dcr-1 homolog expression in carriers of germline mutations, which causes impairment of micro-ribonucleic acid processing and deregulates the growth and differentiation of target cells, leading to an increased risk...

  6. A novel tumor-associated antigen expressed in human uterine and ovarian carcinomas.

    Science.gov (United States)

    Sonoda, K; Nakashima, M; Kaku, T; Kamura, T; Nakano, H; Watanabe, T

    1996-04-15

    A large number of monoclonal antibodies (MoAbs) against human tumor cells have been generated and it has been shown that these MoAbs are useful tools in the diagnosis and treatment of cancer patients, as well as in the basic investigation of the oncogenesis and characterization of cancer cells. The 22-1-1 MoAb was established by cell fusion between mouse myeloma cells and spleen cells derived from mice immunized with the human uterine cervical adenocarcinoma cell line, SiSo. The tissue distribution and biologic characteristics of the 22-1-1 antigen (Ag) were examined. The 22-1-1 Ag was distinct from the known tumor-associated antigens such as YH 206, GA 733, CA 125, carcinoembryonic antigen, and sialyl Le(x) molecules in an expression pattern in human tumor cell lines. An immunohistochemical study revealed that 22-1-1 Ag was expressed in 87.5% of uterine cervical adenocarcinomas, 66% of uterine endometrial adenocarcinomas, and 58.8% of ovarian carcinomas. Moreover, 22-1-1 Ag was detected in 87.7% of uterine cervical squamous cell carcinomas; however, it was not detected in 87.7% of uterine cervical or ovarian tissues, except in uterine endometrial glands, in which its expression was observed at low levels. The 22-1-1 Ag was secreted into cell culture supernatant fluids and was also detected in the vaginal discharges of uterine cervical carcinoma patients. The antigenic epitope of 22-1-1 Ag was shown to be a protein with a molecular weight of 78 kilodaltons using sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. The 22-1-1 MoAb reactive to a novel tumor-associated antigen was generated. This Ag was expressed in cancer cells derived mainly from the uterus and ovary. Moreover, 22-1-1 Ag was associated in the vaginal discharges of uterine cervical carcinoma patients. 22-1-1 MoAb is a potential tool for the study of oncogenesis and the management of cancer patients.

  7. Low or undetectable TPO receptor expression in malignant tissue and cell lines derived from breast, lung, and ovarian tumors

    Directory of Open Access Journals (Sweden)

    Erickson-Miller Connie L

    2012-09-01

    Full Text Available Abstract Background Numerous efficacious chemotherapy regimens may cause thrombocytopenia. Thrombopoietin receptor (TPO-R agonists, such as eltrombopag, represent a novel approach for the treatment of chemotherapy-induced thrombocytopenia. The TPO-R MPL is expressed on megakaryocytes and megakaryocyte precursors, although little is known about its expression on other tissues. Methods Breast, lung, and ovarian tumor samples were analyzed for MPL expression by microarray and/or quantitative reverse transcription-polymerase chain reaction (qRT-PCR, and for TPO-R protein expression by immunohistochemistry (IHC. Cell line proliferation assays were used to analyze the in vitro effect of eltrombopag on breast, lung, and ovarian tumor cell proliferation. The lung carcinoma cell lines were also analyzed for TPO-R protein expression by Western blot. Results MPL mRNA was not detectable in 118 breast tumors and was detectable at only very low levels in 48% of 29 lung tumors studied by microarray analysis. By qRT-PCR, low but detectable levels of MPL mRNA were detectable in some normal (14-43% and malignant (3-17% breast, lung, and ovarian tissues. A comparison of MPL to EPOR, ERBB2, and IGF1R mRNA demonstrates that MPL mRNA levels were far lower than those of EPOR and ERBB2 mRNA in the same tissues. IHC analysis showed negligible TPO-R protein expression in tumor tissues, confirming mRNA analysis. Culture of breast, lung, and ovarian carcinoma cell lines showed no increase, and in fact, showed a decrease in proliferation following incubation with eltrombopag. Western blot analyses revealed no detectable TPO-R protein expression in the lung carcinoma cell lines. Conclusions Multiple analyses of breast, lung, and ovarian tumor samples and/or cell lines show no evidence of MPL mRNA or TPO-R protein expression. Eltrombopag does not stimulate growth of breast, lung, or ovarian tumor cell lines at doses likely to exert their actions on megakaryocytes and

  8. Low or undetectable TPO receptor expression in malignant tissue and cell lines derived from breast, lung, and ovarian tumors.

    Science.gov (United States)

    Erickson-Miller, Connie L; Pillarisetti, Kodandaram; Kirchner, Jennifer; Figueroa, David J; Ottesen, Lone; Martin, Anne-Marie; Liu, Yuan; Kamel, Yasser Mostafa; Messam, Conrad

    2012-09-11

    Numerous efficacious chemotherapy regimens may cause thrombocytopenia. Thrombopoietin receptor (TPO-R) agonists, such as eltrombopag, represent a novel approach for the treatment of chemotherapy-induced thrombocytopenia. The TPO-R MPL is expressed on megakaryocytes and megakaryocyte precursors, although little is known about its expression on other tissues. Breast, lung, and ovarian tumor samples were analyzed for MPL expression by microarray and/or quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and for TPO-R protein expression by immunohistochemistry (IHC). Cell line proliferation assays were used to analyze the in vitro effect of eltrombopag on breast, lung, and ovarian tumor cell proliferation. The lung carcinoma cell lines were also analyzed for TPO-R protein expression by Western blot. MPL mRNA was not detectable in 118 breast tumors and was detectable at only very low levels in 48% of 29 lung tumors studied by microarray analysis. By qRT-PCR, low but detectable levels of MPL mRNA were detectable in some normal (14-43%) and malignant (3-17%) breast, lung, and ovarian tissues. A comparison of MPL to EPOR, ERBB2, and IGF1R mRNA demonstrates that MPL mRNA levels were far lower than those of EPOR and ERBB2 mRNA in the same tissues. IHC analysis showed negligible TPO-R protein expression in tumor tissues, confirming mRNA analysis. Culture of breast, lung, and ovarian carcinoma cell lines showed no increase, and in fact, showed a decrease in proliferation following incubation with eltrombopag. Western blot analyses revealed no detectable TPO-R protein expression in the lung carcinoma cell lines. Multiple analyses of breast, lung, and ovarian tumor samples and/or cell lines show no evidence of MPL mRNA or TPO-R protein expression. Eltrombopag does not stimulate growth of breast, lung, or ovarian tumor cell lines at doses likely to exert their actions on megakaryocytes and megakaryocyte precursors.

  9. Genetic variation in insulin-like growth factor 2 may play a role in ovarian cancer risk

    OpenAIRE

    Pearce, Celeste Leigh; Doherty, Jennifer A.; Van Den Berg, David J.; Moysich, Kirsten; Hsu, Chris; Cushing-Haugen, Kara L.; Conti, David V.; Ramus, Susan J.; Gentry-Maharaj, Aleksandra; Menon, Usha; Gayther, Simon A.; Pharoah, Paul D.P.; Song, Honglin; Kjaer, Susanne K.; Hogdall, Estrid

    2011-01-01

    The insulin-like growth factor (IGF) signaling axis plays an important role in cancer biology. We hypothesized that genetic variation in this pathway may influence risk of ovarian cancer. A three-center study of non-Hispanic whites including 1880 control women, 1135 women with invasive epithelial ovarian cancer and 321 women with borderline epithelial ovarian tumors was carried out to test the association between tag single-nucleotide polymorphisms (tSNPs) (n=58) in this pathway and risk of o...

  10. The contribution of genetic and epigenetic changes in granulosa cell tumors of ovarian origin.

    Science.gov (United States)

    Dhillon, Varinderpal S; Aslam, Mohammad; Husain, Syed Akhtar

    2004-08-15

    Granulosa cell tumors (GCTs) are relatively rare and are subtypes of the sex-cord stromal neoplasms. A better understanding of the molecular genetics underlying various steps in malignant transformation is critical to success in the battle against this disease. Changes in the status of methylation, known as epigenetic alterations, are one of the most common molecular alterations in human cancers, including GCTs. Chromosomal instability and microsatellite instability (MSI) are common in these GCTs. We tested the hypothesis that C-->T transition polymorphism in the promoter region of cytosine DNA-methyltransferase-3B (DNMT3B) and its altered expression are also associated with hypermethylation of the genes. We also attempted to determine the relationship between MSI of ovarian carcinoma and hMLH1 hypermethylation in these tumors. We studied chromosome instability in 25 GCTs by detecting gross chromosome rearrangements in cultured peripheral blood lymphocytes. MSI was assessed using six microsatellite markers (BAT25, BAT26, D2S123, D5S346, D11S1318, and D17S250). Using sensitive methylation-specific PCR, we searched for aberrant promoter hypermethylation in a panel of genes including p16, BRCA1, RASSF1A, ER-alpha, TMS1, TIMP3, Twist, GSTP1, AR, and hMLH1. Polymorphism in the DNMT3B gene was assessed by the PCR-RFLP method, and DNMT3B expression was studied by reverse transcription-PCR assay. Chromosome instability was indicated by significantly higher frequencies of chromosome aberrations (6.24%; P changes include trisomy 14 and monosomy 22. MSI has been found in 19 of 25 tumors, and loss of heterozygosity has been found in 9 of 25 tumors. Frequencies of methylation in GCTs were 40% for p16 and ER-alpha; 36% for BRCA1 and RASSF1A; 28% for hMLH1; 24% for TIMP3, Twist, and GSTP1; and 20% in TMS1 and AR. TT genotype was found only in two cases; the remainder were either CC or CT type. There was no significant alteration in the expression of DNMT3B in these patients

  11. Distinct and competitive regulatory patterns of tumor suppressor genes and oncogenes in ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Min Zhao

    Full Text Available So far, investigators have found numerous tumor suppressor genes (TSGs and oncogenes (OCGs that control cell proliferation and apoptosis during cancer development. Furthermore, TSGs and OCGs may act as modulators of transcription factors (TFs to influence gene regulation. A comprehensive investigation of TSGs, OCGs, TFs, and their joint target genes at the network level may provide a deeper understanding of the post-translational modulation of TSGs and OCGs to TF gene regulation.In this study, we developed a novel computational framework for identifying target genes of TSGs and OCGs using TFs as bridges through the integration of protein-protein interactions and gene expression data. We applied this pipeline to ovarian cancer and constructed a three-layer regulatory network. In the network, the top layer was comprised of modulators (TSGs and OCGs, the middle layer included TFs, and the bottom layer contained target genes. Based on regulatory relationships in the network, we compiled TSG and OCG profiles and performed clustering analyses. Interestingly, we found TSGs and OCGs formed two distinct branches. The genes in the TSG branch were significantly enriched in DNA damage and repair, regulating macromolecule metabolism, cell cycle and apoptosis, while the genes in the OCG branch were significantly enriched in the ErbB signaling pathway. Remarkably, their specific targets showed a reversed functional enrichment in terms of apoptosis and the ErbB signaling pathway: the target genes regulated by OCGs only were enriched in anti-apoptosis and the target genes regulated by TSGs only were enriched in the ErbB signaling pathway.This study provides the first comprehensive investigation of the interplay of TSGs and OCGs in a regulatory network modulated by TFs. Our application in ovarian cancer revealed distinct regulatory patterns of TSGs and OCGs, suggesting a competitive regulatory mechanism acting upon apoptosis and the ErbB signaling pathway through

  12. Tuberculose Pélvica Simulando Tumor Ovariano: a Case Report Pelvic Tuberculosis Simulating Ovarian Tumor

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    Marcelo Ivo Campagnolo

    2000-09-01

    Full Text Available A tuberculose pélvica é uma forma de tuberculose extrapulmonar cuja incidência vem aumentando no mundo ocidental. Esta entidade freqüentemente é acompanhada de achados clínicos e laboratoriais que podem ser inespecíficos e mimetizar outras doenças, inclusive neoplasias ginecológicas. Os autores apresentam um caso de tuberculose pélvica associada à tuberculose peritoneal do abdome em uma mulher de 53 anos, que foi submetida a avaliação laboratorial extensa, incluindo laparoscopia diagnóstica, dosagem de CA-125 e reação de Mantoux. Os aspectos clinicopatológicos e os meios propedêuticos para elucidar o caso são discutidos.Pelvic tuberculosis is an extrapulmonary form of tuberculosis with increasing incidence in the western world. Clinical and laboratory findings of this disease are often unspecific and mimic a variety of other disorders, including gynecologic malignant tumors. The authors report a case of a 53-year-old woman with pelvic tuberculosis and associated abdominal tuberculous peritonitis. Laboratory investigation included laparoscopy, CA-125 levels and tuberculin test, among others. Discussion on the clinicopathological aspects and diagnostic methods used to elucidate this case is presented.

  13. Molecular Characteristics of Malignant Ovarian Germ Cell Tumors and Comparison With Testicular Counterparts: Implications for Pathogenesis

    Science.gov (United States)

    Kraggerud, Sigrid Marie; Hoei-Hansen, Christina E.; Alagaratnam, Sharmini; Skotheim, Rolf I.; Abeler, Vera M.

    2013-01-01

    This review focuses on the molecular characteristics and development of rare malignant ovarian germ cell tumors (mOGCTs). We provide an overview of the genomic aberrations assessed by ploidy, cytogenetic banding, and comparative genomic hybridization. We summarize and discuss the transcriptome profiles of mRNA and microRNA (miRNA), and biomarkers (DNA methylation, gene mutation, individual protein expression) for each mOGCT histological subtype. Parallels between the origin of mOGCT and their male counterpart testicular GCT (TGCT) are discussed from the perspective of germ cell development, endocrinological influences, and pathogenesis, as is the GCT origin in patients with disorders of sex development. Integrated molecular profiles of the 3 main histological subtypes, dysgerminoma (DG), yolk sac tumor (YST), and immature teratoma (IT), are presented. DGs show genomic aberrations comparable to TGCT. In contrast, the genome profiles of YST and IT are different both from each other and from DG/TGCT. Differences between DG and YST are underlined by their miRNA/mRNA expression patterns, suggesting preferential involvement of the WNT/β-catenin and TGF-β/bone morphogenetic protein signaling pathways among YSTs. Characteristic protein expression patterns are observed in DG, YST and IT. We propose that mOGCT develop through different developmental pathways, including one that is likely shared with TGCT and involves insufficient sexual differentiation of the germ cell niche. The molecular features of the mOGCTs underline their similarity to pluripotent precursor cells (primordial germ cells, PGCs) and other stem cells. This similarity combined with the process of ovary development, explain why mOGCTs present so early in life, and with greater histological complexity, than most somatic solid tumors. PMID:23575763

  14. IMP3 expression in human ovarian cancer is associated with improved survival

    DEFF Research Database (Denmark)

    Noske, Aurelia; Faggad, Areeg; Wirtz, Ralph

    2009-01-01

    investigated the expression of IMP3 at protein and mRNA levels in a cohort of primary ovarian carcinomas and in 11 ovarian cancer cell lines. Western blot analysis revealed an expression of IMP3 in all ovarian cancer cell lines and immunohistochemistry demonstrated a positive cytoplasmic staining in 32 of 68...... carcinomas (47%). In contrast, epithelium of borderline tumors, as well as, benign ovarian lesions and normal ovaries exhibited only weak or no IMP3 expression. In univariate Kaplan-Meier analysis, IMP3 protein expression was significantly associated with better overall survival (P=0.048). To confirm......The insulin-like growth factor-II mRNA-binding protein IMP3 plays an important role in embryogenesis and recent reports suggest an involvement in tumorigenesis. Although IMP3 expression has been well studied in mouse and human fetal and adult gonads, its role in ovarian cancer is unknown. We...

  15. Pre-treatment prediction of chemoresistance in second-line chemotherapy of ovarian carcinoma: value of serological tumor marker determination (tetranectin, YKL-40, CASA, CA 125)

    DEFF Research Database (Denmark)

    Grønlund, B; Høgdall, E V S; Christensen, Ib Jarle

    2006-01-01

    OBJECTIVE: To examine if the determination of the levels of serological tumor markers at time of relapse had any predictive value for chemoresistance in the second-line treatment of ovarian cancer patients. METHODS: From a registry of consecutive single-institution patients with epithelial ovarian...... carcinoma pretreated with paclitaxel plus platinum, we selected 82 patients with (a) solid tumor recurrence, and (b) second-line chemotherapy consisting of topotecan (platinum-resistant disease) or paclitaxel plus carboplatin (platinum-sensitive disease). Stored serum samples were analyzed...... of CASA or YKL-40, are associated with increased risk of second-line chemoresistance in patients with ovarian cancer....

  16. Analysis of the Mitogen-activated protein kinase kinase 4 (MAP2K4) tumor suppressor gene in ovarian cancer

    International Nuclear Information System (INIS)

    Davis, Sally J; Choong, David YH; Ramakrishna, Manasa; Ryland, Georgina L; Campbell, Ian G; Gorringe, Kylie L

    2011-01-01

    MAP2K4 is a putative tumor and metastasis suppressor gene frequently found to be deleted in various cancer types. We aimed to conduct a comprehensive analysis of this gene to assess its involvement in ovarian cancer. We screened for mutations in MAP2K4 using High Resolution Melt analysis of 149 primary ovarian tumors and methylation at the promoter using Methylation-Specific Single-Stranded Conformation Polymorphism analysis of 39 tumors. We also considered the clinical impact of changes in MAP2K4 using publicly available expression and copy number array data. Finally, we used siRNA to measure the effect of reducing MAP2K4 expression in cell lines. In addition to 4 previously detected homozygous deletions, we identified a homozygous 16 bp truncating deletion and a heterozygous 4 bp deletion, each in one ovarian tumor. No promoter methylation was detected. The frequency of MAP2K4 homozygous inactivation was 5.6% overall, and 9.8% in high-grade serous cases. Hemizygous deletion of MAP2K4 was observed in 38% of samples. There were significant correlations of copy number and expression in three microarray data sets. There was a significant correlation between MAP2K4 expression and overall survival in one expression array data set, but this was not confirmed in an independent set. Treatment of JAM and HOSE6.3 cell lines with MAP2K4 siRNA showed some reduction in proliferation. MAP2K4 is targeted by genetic inactivation in ovarian cancer and restricted to high grade serous and endometrioid carcinomas in our cohort

  17. Establishment of Patient-Derived Tumor Xenograft Models of Epithelial Ovarian Cancer for Preclinical Evaluation of Novel Therapeutics.

    Science.gov (United States)

    Liu, Joyce F; Palakurthi, Sangeetha; Zeng, Qing; Zhou, Shan; Ivanova, Elena; Huang, Wei; Zervantonakis, Ioannis K; Selfors, Laura M; Shen, Yiping; Pritchard, Colin C; Zheng, Mei; Adleff, Vilmos; Papp, Eniko; Piao, Huiying; Novak, Marian; Fotheringham, Susan; Wulf, Gerburg M; English, Jessie; Kirschmeier, Paul T; Velculescu, Victor E; Paweletz, Cloud; Mills, Gordon B; Livingston, David M; Brugge, Joan S; Matulonis, Ursula A; Drapkin, Ronny

    2017-03-01

    Purpose: Ovarian cancer is the leading cause of death from gynecologic malignancy in the United States, with high rates of recurrence and eventual resistance to cytotoxic chemotherapy. Model systems that allow for accurate and reproducible target discovery and validation are needed to support further drug development in this disease. Experimental Design: Clinically annotated patient-derived xenograft (PDX) models were generated from tumor cells isolated from the ascites or pleural fluid of patients undergoing clinical procedures. Models were characterized by IHC and by molecular analyses. Each PDX was luciferized to allow for reproducible in vivo assessment of intraperitoneal tumor burden by bioluminescence imaging (BLI). Plasma assays for CA125 and human LINE-1 were developed as secondary tests of in vivo disease burden. Results: Fourteen clinically annotated and molecularly characterized luciferized ovarian PDX models were generated. Luciferized PDX models retain fidelity to both the nonluciferized PDX and the original patient tumor, as demonstrated by IHC, array CGH, and targeted and whole-exome sequencing analyses. Models demonstrated diversity in specific genetic alterations and activation of PI3K signaling pathway members. Response of luciferized PDX models to standard-of-care therapy could be reproducibly monitored by BLI or plasma markers. Conclusions: We describe the establishment of a collection of 14 clinically annotated and molecularly characterized luciferized ovarian PDX models in which orthotopic tumor burden in the intraperitoneal space can be followed by standard and reproducible methods. This collection is well suited as a platform for proof-of-concept efficacy and biomarker studies and for validation of novel therapeutic strategies in ovarian cancer. Clin Cancer Res; 23(5); 1263-73. ©2016 AACR . ©2016 American Association for Cancer Research.

  18. Risk of Ovarian Cancer and the NF-κB Pathway

    DEFF Research Database (Denmark)

    Charbonneau, Bridget; Block, Matthew S; Bamlet, William R

    2014-01-01

    participants in the prior study (OR, 0.85; 95% CI, 0.75-0.95; P = 0.006). Considering a multiple-testing-corrected significance threshold of P ovarian cancer (low malignant potential tumors OR, 0.......85; 95% CI, 0.79-0.91; P = 0.00002). Our results extend the evidence that borderline tumors may have a distinct genetic etiology. Further investigation of how these SNPs might modify ovarian cancer associations with other inflammation-related risk factors is warranted.......A missense single-nucleotide polymorphism (SNP) in the immune modulatory gene IL1A has been associated with ovarian cancer risk (rs17561). Although the exact mechanism through which this SNP alters risk of ovarian cancer is not clearly understood, rs17561 has also been associated with risk...

  19. Changes in Local Immunity Factors in Women with Pre-Existing Cervical Disease and Benign Ovarian Tumors

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    Nazar Matviykiv

    2017-10-01

    Full Text Available The objective of the research was to study the indices of local immunity in relation to the hormonal state of the body in women with benign ovarian tumors and pre-existing cervical diseases. Materials and methods. The concentration of major gonadotropic and steroid hormones during the female ovarian and menstrual cycle, as well as individual local immunity factors of proinflammatory cytokines and secretory immunoglobulin A was studied in 40 patients with benign ovarian tumors and pre-existing cervical diseases. Results and discussion. In the second phase of the ovarian and menstrual cycle, a significant reduction (by 3.0 times in the concentration of progesterone and relative hypoestrogenism (by 1.5 times as compared to the control data were found. Anovulation was observed in 40.00% of cases and corpus luteum deficiency syndrome was diagnosed in 62.5% of women. The assessment of secretory immunoglobulin A concentration allowed us to note (along with the hypersecretion of proinflammatory cytokines an increase in this marker in half of the examined women in the presence of chronic cervicitis and vaginitis, candidiasis and viral lesion - along with the activation of proinflammatory cytokine depression of secretory immunoglobulin A synthesis as compared to the control data. Conclusions. Local immunity changes in women with benign ovarian tumors and pre-existing cervical diseases are accompanied by abnormalities of the hormonal profile and the association of maladaptive changes in the system of local immunity manifested by fluctuations in the level of secretory immunoglobulin A during the secretory phase of the menstrual cycle and an increase in proinflammatory cytokine synthesis. The results of the conducted study allowed us to note a significant increase in the concentration of secretory immunoglobulin A along with the activation of proinflammatory cytokine synthesis in most women with benign ovarian tumors and pre-existing cervical diseases which

  20. The humanized anti-human AMHRII mAb 3C23K exerts an anti-tumor activity against human ovarian cancer through tumor-associated macrophages.

    Science.gov (United States)

    Bougherara, Houcine; Némati, Fariba; Nicolas, André; Massonnet, Gérald; Pugnière, Martine; Ngô, Charlotte; Le Frère-Belda, Marie-Aude; Leary, Alexandra; Alexandre, Jérôme; Meseure, Didier; Barret, Jean-Marc; Navarro-Teulon, Isabelle; Pèlegrin, André; Roman-Roman, Sergio; Prost, Jean-François; Donnadieu, Emmanuel; Decaudin, Didier

    2017-11-21

    Müllerian inhibiting substance, also called anti-Müllerian hormone (AMH), inhibits proliferation and induces apoptosis of AMH type II receptor-positive tumor cells, such as human ovarian cancers (OCs). On this basis, a humanized glyco-engineered monoclonal antibody (3C23K) has been developed. The aim of this study was therefore to experimentally confirm the therapeutic potential of 3C23K in human OCs. We first determined by immunofluorescence, immunohistochemistry and cytofluorometry analyses the expression of AMHRII in patient's tumors and found that a majority (60 to 80% depending on the detection technique) of OCs were positive for this marker. We then provided evidence that the tumor stroma of OC is enriched in tumor-associated macrophages and that these cells are responsible for 3C23K-induced killing of tumor cells through ADCP and ADCC mechanisms. In addition, we showed that 3C23K reduced macrophages induced-T cells immunosuppression. Finally, we evaluated the therapeutic efficacy of 3C23K alone and in combination with a carboplatin-paclitaxel chemotherapy in a panel of OC Patient-Derived Xenografts. In those experiments, we showed that 3C23K significantly increased the proportion and the quality of chemotherapy-based in vivo responses. Altogether, our data support the potential interest of AMHRII targeting in human ovarian cancers and the evaluation of 3C23K in further clinical trials.

  1. miR-761 inhibits tumor progression by targeting MSI1 in ovarian carcinoma.

    Science.gov (United States)

    Shi, Can; Zhang, Zhenyu

    2016-04-01

    Increasing evidences have revealed that microRNAs regulate various biological processes. However, the roles of miR-761 have not been investigated in ovarian cancer. Here, we found that miR-761 expression was significantly lower in ovarian cancer tissues than in their paired noncancerous tissues. Further study revealed that miR-761 overexpression inhibited the ovarian cancer cell proliferation and invasion. Mechanistically, we demonstrated that the oncogenic properties of miR-761 in ovarian cancer were mediated in part by regulating MSI1 expression. miR-761 and MSI1 are inversely expressed in ovarian cancer tissues. In conclusion, we demonstrated that miR-761 repressed ovarian cancer proliferation and invasion by targeting MSI1.

  2. Recent Concepts of Ovarian Carcinogenesis: Type I and Type II

    Directory of Open Access Journals (Sweden)

    Masafumi Koshiyama

    2014-01-01

    Full Text Available Type I ovarian tumors, where precursor lesions in the ovary have clearly been described, include endometrioid, clear cell, mucinous, low grade serous, and transitional cell carcinomas, while type II tumors, where such lesions have not been described clearly and tumors may develop de novo from the tubal and/or ovarian surface epithelium, comprise high grade serous carcinomas, undifferentiated carcinomas, and carcinosarcomas. The carcinogenesis of endometrioid and clear cell carcinoma (CCC arising from endometriotic cysts is significantly influenced by the free iron concentration, which is associated with cancer development through the induction of persistent oxidative stress. A subset of mucinous carcinomas develop in association with ovarian teratomas; however, the majority of these tumors do not harbor any teratomatous component. Other theories of their origin include mucinous metaplasia of surface epithelial inclusions, endometriosis, and Brenner tumors. Low grade serous carcinomas are thought to evolve in a stepwise fashion from benign serous cystadenoma to a serous borderline tumor (SBT. With regard to high grade serous carcinoma, the serous tubal intraepithelial carcinomas (STICs of the junction of the fallopian tube epithelium with the mesothelium of the tubal serosa, termed the “tubal peritoneal junction” (TPJ, undergo malignant transformation due to their location, and metastasize to the nearby ovary and surrounding pelvic peritoneum. Other theories of their origin include the ovarian hilum cells.

  3. Diagnostic accuracy of risk of malignancy index in predicting complete tumor removal at primary debulking surgery for ovarian cancer patients

    DEFF Research Database (Denmark)

    Fagö-Olsen, Carsten L; Håkansson, Fanny; Antonsen, Sofie L

    2013-01-01

    to investigate whether the risk of malignancy index (RMI) was a useful marker for this evaluation. RMI and surgical outcome were investigated in 164 patients, 49 of whom had no residual tumor after PDS. The receiver operating characteristic curve showed an area under the curve of 0.72 (confidence interval: 0......Ovarian cancer patients in whom complete tumor removal is impossible with primary debulking surgery (PDS) may benefit from neoadjuvant chemotherapy and interval debulking surgery. However, the task of performing a pre-operative evaluation of the feasibility of PDS is difficult. We aimed.......64-0.80). The possibility of complete tumor removal decreased with increasing RMI and there was a tendency towards higher RMI in patients with residual tumor after PDS, but no single cut-off value of RMI produced useful clinical predictive values. In conclusion, RMI alone is not an optimal method to determine whether...

  4. The prognostic value of dividing epithelial ovarian cancer into type I and type II tumors based on pathologic characteristics

    DEFF Research Database (Denmark)

    Prahm, Kira Philipsen; Karlsen, Mona Aarenstrup; Høgdall, Estrid

    2015-01-01

    OBJECTIVE: To investigate the prognostic significance of dividing epithelial ovarian cancer (EOC) in type I and type II tumors based on pathologic variables. METHODS: We used the Danish Gynecologic Cancer Database to identify all patients diagnosed with EOC from 2005 to 2012. Information...... on histologic type and grade were used to classify tumors as either type I or type II. Death, and several prognostic factors were used in the multivariate Cox regression, and Landmark analysis was used to estimate hazard ratios of all-cause mortality. RESULTS: Among 2660 patients diagnosed with EOC, 735 were...... categorized as type I tumors, and 1925 as type II tumors. Patients with type II EOC were more frequently diagnosed in late FIGO stages (stages III-IV) than patients with type I EOC (78.1% vs. 32.1% respectively; P

  5. Ovarian cancer

    International Nuclear Information System (INIS)

    Wakabayashi, Yukari; Yachida, Meri; Akata, Soichi; Kawana, Koji; Kotake, Fumio; Kakizaki, Dai; Abe, Kimihiko; Negishi, Noriyuki; Akiya, Kiyoshi

    1988-01-01

    In 40 patients undergoing pre-treatment for an ovarian tumor, a CT scan of the pelvis and measurements of their CA 125, CA 19 - 9, IAP (immunosupressive acidic antigen), and TPA (tissue polypeptide antigen were performed. The specificity and sensitivity of the CT diagnosis was found to be better than any of other tumor markers measurements. Comparison of the 4 markers showed that the CA 125 testing had the greatest sensitivity in detecting an ovarian cancer. Moreover, the sensitivity of CA 125, was better than a combination of the 4 markers. Thus, a CT scan still remains necessary for the diagnosis of an ovarian cancer. (author)

  6. Clinical implication of Tiam1 overexpression in the prognosis of patients with serous ovarian carcinoma.

    Science.gov (United States)

    Li, Huiwen; Cui, Xuelian; Chen, Dingbao; Yang, Yang; Piao, Junjie; Lin, Zhenhua; Yan, Guanghai; Shen, Danhua

    2016-11-01

    T lymphoma invasion and metastasis 1 ( Tiam1 ), a guanine nucleotide exchange factor, was originally identified as an invasion- and metastasis-inducing gene in T lymphoma cells. High expression levels of the human Tiam1 gene have been found in numerous human malignancies, suggesting a potential role as a modifier of tumor initiation and progression. However, little is known about the status of Tiam1 in ovarian carcinoma. The present study aimed to investigate the clinicopathological significance of high Tiam1 expression in serous ovarian carcinoma. Immunohistochemical staining for Tiam1 was performed in 182 patients with serous ovarian carcinoma, in 76 patients with ovarian borderline tumors and in 72 patients with benign ovarian tumors. Immunofluorescence staining was also performed to detect the subcellular localization of Tiam1 protein in SK-OV-3 ovarian carcinoma cells. The correlations between high Tiam1 expression and the clinicopathological features of the ovarian carcinomas were evaluated by the χ 2 test and Fisher's exact test. The overall survival (OS) rates were calculated by the Kaplan-Meier method, and the association between prognostic factors and patient survival was analyzed by the Cox proportional hazard model. Tiam1 protein showed a cytoplasmic and nuclear staining pattern in ovarian carcinoma. Strongly-positive Tiam1 protein expression was observed in 59.3% (108/182) of ovarian carcinomas, which was significantly higher than in benign serous tumors (12.5%; 9/72). Moreover, the rate of strongly-positive Tiam1 expression in borderline serous tumors (31.6%; 24/76) was also significantly higher than that in benign serous tumors. High Tiam1 protein expression was closely associated with a high histological grade, metastasis, advanced clinical stage and lower OS rates in ovarian carcinoma. Multivariate analysis indicated that Tiam1 was an independent prognostic factor, along with metastasis and clinical stage, in patients with ovarian carcinoma. In

  7. Immunologic aspect of ovarian cancer and p53 as tumor antigen

    NARCIS (Netherlands)

    Nijman, HW; Lambeck, A; van der Burg, SH; van der Zee, AGJ; Daemen, T

    2005-01-01

    Ovarian cancer represents the fifth leading cause of death from all cancers for women. During the last decades overall survival has improved due to the use of new chemotherapy schedules. Still, the majority of patients die of this disease. Research reveals that ovarian cancer patients exhibit

  8. Histopathological Pattern and Age Distribution, of Malignant Ovarian Tumor among Sudanese Ladies

    Directory of Open Access Journals (Sweden)

    Sumeya A. Khieri

    2018-02-01

    CONCLUSION: The incidence of different types of ovarian cancers in the present study is similar to worldwide incidence. The surface epithelial tumour is the commonest ovarian cancer, of which serous adenocarcinoma is the commonest and most of our patients present in late stages.

  9. The association between the p53/topoisomerase I and p53/ topoisomerase IIalpha immunophenotypes and the progression of ovarian carcinomas.

    Science.gov (United States)

    Bar, Julia K; Grelewski, Piotr; Noga, Leszek; Rabczyński, Jerzy; Gryboś, Marian; Jeleń, Michał

    2012-01-01

    In in vitro studies it has been revealed that p53 protein expression might regulate topoisomerase I (topo I) and topoisomerase IIalpha (topo IIalpha) levels in tumor cells. So far, the association between the p53 protein and topo I and topo IIalpha expression and its impact on ovarian carcinoma progression has not been analyzed. The aim of the study was to examine the association between topo I and topo IIalpha expression and p53 protein overexpression with respect to the morphological features and progressive growth of ovarian tumors. The expression of the studied biomarkers was estimated by immunohistochemical staining in tumor sections from 136 malignant and 30 benign ovarian neoplasms. Significant differences for topo I, topo IIalpha and p53 expression between malignant and benign tumors were observed (p p53 protein was associated with advanced stages of ovarian carcinomas (p ovarian carcinomas, positive correlations between topo I and topo IIalpha, topo I and p53 and topo Ilalpha and p53 protein expression were revealed (p = 0.001). No relationship between the studied biomarkers was found in benign ovarian tumors (p > 0.05). p53/topo I and p53/topo IIalpha immunophenotypes were associated with advanced stages of ovarian carcinoma (p = 0.045 and p = 0.009, respectively), p53/topo IIalpha positive ovarian carcinomas were more frequently observed in high than in low tumor grades and the differences were only of borderline significance (p = 0.07). Current findings suggest that on the one hand, cooperation between topo I, topo IIalpha and p53 protein participates in the progressive growth of ovarian tumors. On the other hand, simultaneous expression of the studied proteins identifies the subgroup of ovarian cancers with aggressive biological features which might be considered in therapy.

  10. [Third National Ovarian Consensus. 2011. Grupo de Investigación en Cáncer de Ovario y Tumores Ginecológicos de México "GICOM"].

    Science.gov (United States)

    Gallardo-Rincón, Dolores; Cantú-de-León, David; Alanís-López, Patricia; Alvarez-Avitia, Miguel Angel; Bañuelos-Flores, Joel; Herbert-Núñez, Guillermo Sidney; Oñate-Ocaña, Luis Fernando; Pérez-Montiel, María Delia; Rodríguez-Trejo, Amelia; Ruvalcaba-Limón, Eva; Serrano-Olvera, Alberto; Ortega-Rojo, Andrea; Cortés-Esteban, Patricia; Erazo-Valle, Aura; Gerson-Cwilich, Raquel; De-la-Garza-Salazar, Jaime; Green-Renner, Dan; León-Rodríguez, Eucario; Morales-Vásquez, Flavia; Poveda-Velasco, Andrés; Aguilar-Ponce, José Luis; Alva-López, Luis Felipe; Alvarado-Aguilar, Salvador; Alvarado-Cabrero, Isabel; Aquino-Mendoza, Cinthia Alejandra; Aranda-Flores, Carlos Eduardo; Bandera-Delgado, Artfy; Barragán-Curiel, Eduardo; Barrón-Rodríguez, Patricia; Brom-Valladares, Rocío; Cabrera-Galeana, Paula Anel; Calderillo-Ruiz, Germán; Camacho-Gutiérrez, Salvador; Capdeville-García, Daniel; Cárdenas-Sánchez, Jesús; Carlón-Zárate, Elisa; Carrillo-Garibaldi, Oscar; Castorena-Roji, Gerardo; Cervantes-Sánchez, Guadalupe; Coronel-Martínez, Jaime Alberto; Chanona-Vilchis, José Gregorio; Díaz-Hernández, Verónica; Escudero-de-los Ríos, Pedro; Garibay-Cerdenares, Olga; Gómez-García, Eva; Herrera-Montalvo, Luis Alonso; Hinojosa-García, Luz María; Isla-Ortiz, David; Jiménez-López, Josefina; Lavín-Lozano, Arturo Javier; Limón-Rodriguez, Jesús Alberto; López-Basave, Horacio Noé; López-García, Sergio César; Maffuz-Aziz, Antonio; Martínez-Cedillo, Jorge; Martínez-López, Dulce María; Medina-Castro, Juan Manuel; Melo-Martínez, Carlos; Méndez-Herrera, Carmen; Montalvo-Esquivel, Gonzalo; Morales-Palomares, Miguel Angel; Morán-Mendoza, Andrés; Morgan-Villela, Gilberto; Mota-García, Aída; Muñoz-González, David Eduardo; Ochoa-Carrillo, Francisco J; Pérez-Amador, Maricruz; Recinos-Money, Edgar; Rivera-Rivera, Samuel; Robles Flores, Juan U; Rojas-Castillo, Edith; Rojas-Marín, Carlos; Salas-Gonzáles, Efraín; Sámano-Nateras, Liliana; Santibañez-Andrade, Miguel; Santillán-Gómez, Antonio; Silva-García, Araceli; Silva, Juan Alejandro; Solorza-Luna, Gilberto; Tabarez-Ortiz, Adán Raúl; Talamás-Rohana, Patricia; Tirado-Gómez, Laura Leticia; Torres-Lobatón, Alfonso; Quijano-Castro, Félix

    2011-01-01

    Ovarian cancer (OC) is the third most common gynecologic malignancy worldwide. Most of cases it is of epithelial origin. At the present time there is not a standardized screening method, which makes difficult the early diagnosis. The 5-year survival is 90% for early stages, however most cases present at advanced stages, which have a 5-year survival of only 5-20%. GICOM collaborative group, under the auspice of different institutions, have made the following consensus in order to make recommendations for the diagnosis and management regarding to this neoplasia. The following recommendations were made by independent professionals in the field of Gynecologic Oncology, questions and statements were based on a comprehensive and systematic review of literature. It took place in the context of a meeting of two days in which a debate was held. These statements are the conclusions reached by agreement of the participant members. No screening method is recommended at the time for the detection of early lesions of ovarian cancer in general population. Staging is surgical, according to FIGO. In regards to the pre-surgery evaluation of the patient, it is recommended to perform chest radiography and CT scan of abdomen and pelvis with IV contrast. According to the histopathology of the tumor, in order to consider it as borderline, the minimum percentage of proliferative component must be 10% of tumor's surface. The recommended standardized treatment includes primary surgery for diagnosis, staging and cytoreduction, followed by adjuvant chemotherapy Surgery must be performed by an Oncologist Gynecologist or an Oncologist Surgeon because inadequate surgery performed by another specialist has been reported in 75% of cases. In regards to surgery it is recommended to perform total omentectomy since subclinic metastasis have been documented in 10-30% of all cases, and systematic limphadenectomy, necessary to be able to obtain an adequate surgical staging. Fertility-sparing surgery will

  11. Cytotoxic drug sensitivity testing of tumor cells from patients with ovarian carcinoma using the fluorometric microculture cytotoxicity assay (FMCA).

    Science.gov (United States)

    Csoka, K; Larsson, R; Tholander, B; Gerdin, E; de la Torre, M; Nygren, P

    1994-08-01

    The automated fluorometric microculture cytotoxicity assay (FMCA) is based on the measurement of fluorescence generated from cellular hydrolysis of fluorescein diacetate (FDA) to fluorescein by viable cells after a 72-hr culture period in microtiter plates. The FMCA was adopted for chemosensitivity testing of tumor cells from patients with ovarian carcinoma. Thirty-seven samples of solid tumors and malignant effusions were obtained from 35 patients at diagnosis or relapse. Tumor cells from solid samples and effusions were prepared by enzymatic digestion and centrifugation, respectively, followed by Percoll or Ficoll purification. The fluorescence was proportional to the number of cells/well and considerably higher in tumor cells than in contaminating normal cells. The effect of up to 19 cytotoxic drugs was successfully assessed in 70% of the samples and there was a good correlation between drug sensitivity data reported by the FMCA and the DiSC assay performed in parallel. The overall drug sensitivity pattern in vitro corresponded well to the clinical experience. The effect of cisplatin varied considerably between patients and resistance was found also in cases not previously exposed to cytotoxic drugs. The FMCA is a rapid and simple method that seems to report clinically relevant cytotoxic drug sensitivity data in ovarian carcinomas. In the future, this method may contribute to optimizing chemotherapy by assisting in individualized drug selection and new drug development.

  12. Identification of glucocorticoid-induced leucine zipper as a key regulator of tumor cell proliferation in epithelial ovarian cancer

    Directory of Open Access Journals (Sweden)

    Fernandez Hervé

    2009-10-01

    Full Text Available Abstract Background Little is known about the molecules that contribute to tumor progression of epithelial ovarian cancer (EOC, currently a leading cause of mortality from gynecological malignancies. Glucocorticoid-Induced Leucine Zipper (GILZ, an intracellular protein widely expressed in immune tissues, has been reported in epithelial tissues and controls some of key signaling pathways involved in tumorigenesis. However, there has been no report on GILZ in EOC up to now. The objectives of the current study were to examine the expression of GILZ in EOC and its effect on tumor cell proliferation. Results GILZ expression was measured by immunohistochemical staining in tissue sections from 3 normal ovaries, 7 benign EOC and 50 invasive EOC. GILZ was not detected on the surface epithelium of normal ovaries and benign tumors. In contrast, it was expressed in the cytoplasm of tumor cells in 80% EOC specimens. GILZ immunostaining scores correlated positively to the proliferation marker Ki-67 (Spearman test in univariate analysis, P P Conclusion The present study is the first to identify GILZ as a molecule produced by ovarian cancer cells that promotes cell cycle progression and proliferation. Our findings clearly indicate that GILZ activates AKT, a crucial signaling molecule in tumorigenesis. GILZ thus appears as a potential key molecule in EOC.

  13. Pathogenesis of Ovarian Serous Carcinoma as the Basis for Immunologic Directed Diagnosis and Treatment

    Science.gov (United States)

    2004-08-01

    Co[ýVr/ lgbt t A eic , n Sc t 1t’.jar lni ttItrtii, I’alogy Review Ovarian Tumorigenesis A Proposed Model Based on Morphological and Molecular...without cytologic atypia ( right inset). B: Epithelial cells lining the cystadenoma (between arrows) were isolated using laser capture microdissection with...specimen. Right panel (case F) shows a point mutation in the BRAF gene in both the serous borderline tumor and the corresponding cystadenoma. Fig. 3

  14. Dieckol, isolated from the edible brown algae Ecklonia cava, induces apoptosis of ovarian cancer cells and inhibits tumor xenograft growth.

    Science.gov (United States)

    Ahn, Ji-Hye; Yang, Yeong-In; Lee, Kyung-Tae; Choi, Jung-Hye

    2015-02-01

    Ecklonia cava is an abundant brown alga and has been reported to possess various bioactive compounds having anti-inflammatory effect. However, the anticancer effects of dieckol, a major active compound in E. cava, are poorly understood. In the present study, we investigated the anti-tumor activity of dieckol and its molecular mechanism in ovarian cancer cells and in a xenograft mouse model . MTT assay, PI staining, and PI and Annexin double staining were performed to study cell cytotoxicity, cell cycle distribution, and apoptosis. We also investigated reactive oxygen species (ROS) production and protein expression using flow cytometry and Western blot analysis, respectively. Anti-tumor effects of dieckol were evaluated in SKOV3 tumor xenograft model. We found that the E. cava extract and its phlorotannins have cytotoxic effects on A2780 and SKOV3 ovarian cancer cells. Dieckol induced the apoptosis of SKOV3 cells and suppressed tumor growth without any significant adverse effect in the SKOV3-bearing mouse model. Dieckol triggered the activation of caspase-8, caspase-9, and caspase-3, and pretreatment with caspase inhibitors neutralized the pro-apoptotic activity of dieckol. Furthermore, treatment with dieckol caused mitochondrial dysfunction and suppressed the levels of anti-apoptotic proteins. We further demonstrated that dieckol induced an increase in intracellular ROS, and the antioxidant N-acetyl-L-cysteine (NAC) significantly reversed the caspase activation, cytochrome c release, Bcl-2 downregulation, and apoptosis that were caused by dieckol. Moreover, dieckol inhibited the activity of AKT and p38, and overexpression of AKT and p38, at least in part, reversed dieckol-induced apoptosis in SKOV3 cells. These data suggest that dieckol suppresses ovarian cancer cell growth by inducing caspase-dependent apoptosis via ROS production and the regulation of AKT and p38 signaling.

  15. Cell-to-cell communication competence in simian virus 40-transfected rat ovarian cells is reduced following tumor selection.

    Science.gov (United States)

    Stein, L S; Welsh, T H; Wilson, V G; Burghardt, R C

    1992-06-01

    A pSV3neo-transfected rat ovarian cell line (SV-GC) was developed from a primary granulosa culture (GC) to study gap junctional intercellular communication (GJIC) during Simian virus 40 (SV40) transformation. SV-GC expressed SV40 large T-antigen (T-ag), grew indefinitely in culture without luteinization, was anchorage independent, and formed tumors in nude mice. Ultrastructural analysis identified abundant gap junctional membrane and suggested that SV-GC was arrested at an early stage of differentiation. Functional GJIC, measured by a dye transfer technique (gap FRAP), was comparable to that observed in normal granulosa cells, suggesting that the expression of T-ag alone was insufficient to reduce GJIC. However, there was approximately a 50% loss in the rate of GJIC in the nude mouse SV-GC-tumor derived and G418 selected cell line (T-SV-GC). SV-GC----T-SV-GC also resulted in a transition from migration of cells as an epithelial sheet to the dissociation of individual fibroblastoid cells. Tumor cell detachment was also seen in migrating malignant human (A2780 and 547) and rat (DC3) ovarian cell lines. Co-culture combinations of normal (GC)----transformed (SV-GC)----tumor-derived (T-SV-GC) cells indicated that the rate of heterologous GJIC was characteristic of the least communicating partner. Taken together, these data suggested that SV-GC----T-SV-GC represented progression toward metastasis with concomitant reduction of GJIC and adhesiveness. These sequentially derived cell lines may be a useful in vitro model system for studies focusing on the mechanism involved in the detachment of cells during the progression of ovarian cancer.

  16. Markers of fibroblast-rich tumor stroma and perivascular cells in serous ovarian cancer : Inter- and intra-patient heterogeneity and impact on survival

    NARCIS (Netherlands)

    Corvigno, Sara; Wisman, G. Bea A.; Mezheyeuski, Artur; van der Zee, Ate G. J.; Nijman, Hans W.; Avall-Lundqvist, Elisabeth; Ostman, Arne; Dahlstrand, Hanna

    2016-01-01

    Inter- and intra-patient variations in tumor microenvironment of serous ovarian cancer are largely unexplored. We aimed to explore potential co-regulation of tumor stroma characteristics, analyze their concordance in primary and metastatic lesions, and study their impact on survival. A tissue

  17. Extremely long tumor retention, multi-responsive boronate crosslinked micelles with superior therapeutic efficacy for ovarian cancer.

    Science.gov (United States)

    Xiao, Wenwu; Suby, Nell; Xiao, Kai; Lin, Tzu-Yin; Al Awwad, Nasir; Lam, Kit S; Li, Yuanpei

    2017-10-28

    Mortality rates for ovarian cancer have declined only slightly in the past forty years since the "War on Cancer" was declared. The current standard care of ovarian cancer is still cytoredutive surgery followed by several cycles of chemotherapy. The severe adverse effect from chemotherapy drug is a leading cause for the patients to fail in long term therapy post-surgery. New nanocarriers able to minimize the premature drug release in blood circulation while releasing drug on-demand at tumor site have profound impact on the improvement of the efficacy and toxicity profile of the chemotherapeutic drugs. Here we reported a unique type of extremely long tumor retention, multi-responsive boronate crosslinked micelles (BCM) for ovarian cancer therapy. We systemically investigated the stability of BCM in serum and plasma, and their responsiveness to acidic pH and cis-diols (such as mannitol, a safe FDA approved drug for diuresis) through particle size measurement and förster resonance energy transfer (FRET) approach. Paclitaxel (PTX) loaded BCM (BCM-PTX) exhibited higher stability than non-crosslinked micelles (NCM) in the presence of plasma or serum. BCMs possessed a longer in vivo blood circulation time when compared to NCM. Furthermore, BCM could be disassembled in an acidic pH environment or by administrating mannitol, facilitating drug release in an acidic tumor environment and triggered by exogenous stimuli after drug enrichment in tumor mass. Near infra-red fluorescence (NIRF) imaging on SKOV-3 ovarian cancer mouse model demonstrated that the NIR dye DiD encapsulated BCM could preferentially accumulate in tumor site and their tumor retention was very long with still 66% remained on 12th day post injection. DiD-NCM had similar high-level uptake in tumor with DiD-BCM within the first 3days, its accumulation, however, decreased obviously on 4th day and only 15% dye was left 12days later. In both formulations, the dye uptake in normal organs was mostly washed away

  18. Human ovarian carcinomas detected by specific odor.

    Science.gov (United States)

    Horvath, György; Järverud, Gunvor Af Klinteberg; Järverud, Sven; Horváth, István

    2008-06-01

    The high mortality rate associated with ovarian carcinoma is mainly owing to late diagnosis. It is thus essential to develop inexpensive and simple methods for early diagnosis. Papers on canine scent detection of malignancies such as melanoma and bladder, lung, and breast cancer have recently been published in peer-reviewed journals, indicating a new diagnostic tool for malignancies. However, in these studies the dogs may have responded to odors associated with cancer, such as inflammation or metabolic products, rather than specifically to cancer itself. Therefore, it is important to ascertain whether or not human cancers are characterized by specific odors. We hypothesized that if ovarian carcinoma emits a specific odor, dogs may be trained to detect it. Using our training method, we taught a dog to distinguish different histopathological types and grades of ovarian carcinomas, including borderline tumors, from healthy control samples. Double-blind tests showed 100% sensitivity and 97.5% specificity. Moreover, the odor of ovarian carcinomas seems to differ from those of other gynecological malignances such cervical, endometrial, and vulvar carcinomas. Our study strongly suggests that the most common ovarian carcinomas are characterized by a single specific odor.

  19. Malignant ovarian germ cell tumors in pediatric patients: The AIEOP (Associazione Italiana Ematologia Oncologia Pediatrica) study.

    Science.gov (United States)

    Terenziani, M; Bisogno, G; Boldrini, R; Cecchetto, G; Conte, M; Boschetti, L; De Pasquale, M D; Biasoni, D; Inserra, A; Siracusa, F; Basso, M E; De Leonardis, F; Di Pinto, D; Barretta, F; Spreafico, F; D'Angelo, P

    2017-11-01

    Malignant ovarian germ cell tumors (MOGCT) carry an excellent prognosis, and the treatment aims to achieve results with the least possible treatment-related morbidity. The aim of this study was to assess the outcomes of pediatric patients with MOGCT. Patients were treated according to their stage: surgery and surveillance for stage I; a modified bleomycin-etoposide-cisplatin (BEP) regimen for stages II (three cycles), III, and IV (three cycles) with surgery on residual disease. Seventy-seven patients were enrolled (median age 11.8 years), 26 with dysgerminoma (Dysg), 13 with immature teratoma and elevated serum alpha-fetoprotein levels (IT + AFP), and 38 with nondysgeminoma (Non-Dysg) staged as follows: 27 stage I, 13 stage II, 32 stage III, 5 stage IV. Among evaluable patients in stage I (5-year event-free survival [EFS] 72.1% [95% CI: 56.4-92.1%]; 5-year overall survival [OS] 100%), seven relapsed (three patients with Dysg and four patients with Non-Dysg) and were rescued with chemotherapy (plus surgery in three patients). Among the evaluable patients with stages II-IV, 48 (98%) achieved complete remission after chemotherapy ± surgery, one (IT + AFP, stage IV) had progressive disease. In the whole series (median follow-up 80 months), the 5-year OS and EFS were 98.5% (95% CI: 95.6-100%) and 84.5% (95% CI: 76.5-93.5%). We confirm the excellent outcome for MOGCT. Robust data are lacking on surgical staging, surveillance for Non-Dysg with stage I, the management of IT + AFP, and the most appropriate BEP regimen. As pediatric oncologists, we support the role of surveillance after proper surgical staging providing cases are managed by experts at specialized pediatric centers. © 2017 Wiley Periodicals, Inc.

  20. Modulators of Response to Tumor Necrosis-related Apoptosis Inducing Ligand (TRAIL) Therapy in Ovarian Cancer

    Science.gov (United States)

    2011-05-01

    Poor Survival. Cancer Res 67: 3036–3042. 22. Fulda S, Scaffidi C, Pietsch T, Krammer PH, Peter ME, et al. (1998) Activation of the CD95 (APO-1/Fas...in ovarian carcinoma causes resistance to TRAIL-mediated apoptosis and is associated with poor survival. Cancer Res 2007; 67:3036-42. 19. Yu Y ...ovarian cancer in remission. 315 Therapeutic efficacy of folate receptor α blockade with MORAb-003 in ovarian cancer W. A. Spannuth1, Y . G. Lin1, W. M

  1. Uterine Didelphys with blind hemivagina, hematocolpos, ipsilateral renal agenesis (UD-BHRA) and bilateral ovarian tumors : a case report

    International Nuclear Information System (INIS)

    Lee, Young Rae; Choi, Byung Ik; Park, Hae Won; Kook, Shin Ho

    1998-01-01

    Uterine didelphys is a congenital malformation characterized by the presence of two separated hemiuteri and hemivaginas, due to lack of midfusion of the mullerian ducts. We report a case of UD-BHRA (uterine didelphys with blind hemivagina and ipsilateral renal agencies), a rare type of uterine dedelphys characterized by symptomatic unilateral hematocolpos due to blind hemivagina after menarche and ipsilateral renal agenesis. The MRI findings in 22-year-old woman with bilateral ovarian tumors demonstrated two separated uterine horns and cervical and vaginal canals, with left hematocolpos and left agenesis. (author). 7 refs., 1 fig

  2. PAX2, PAX8 and CDX2 Expression in Metastatic Mucinous, Primary Ovarian Mucinous and Seromucinous Tumors and Review of the Literature.

    Science.gov (United States)

    Ates Ozdemir, D; Usubutun, A

    2016-07-01

    Ovarian cancer is the most common cause of gynecologic cancer death. Both morphologically and immunohistochemically, metastatic mucinous tumors are the best mimickers of mucinous ovarian tumors; its pathogenesis still remains a mystery. PAX2 and PAX8 immunohisyochemistries are useful for differentiating numerous primary tumour types from metastatic ones. There are few studies in literature about PAX expressions in mucinous and seromucinous tumors. None of these are takes into account the histologic type (whether it is seromucinous or mucinous) or the metastatic origin. With this purpose hematoxylin and eosine slides of ovarian mucinous and seromucinous tumors were re-evaluated and one block was chosen for each case. The study included 76 ovarian mucinous and seromucinous tumors of the ovary reported in Hacettepe University department of pathology between 2000 and 2013. Tissue microarray (TMA) was designed from the chosen blocks, PAX2, PAX8, CDX2 immunostains was preformed to the TMA slides. As a result, most of the metastatic cases were negative for PAX2 (91.2 %) and PAX8 (86.3 %), many were diffusely and strongly positive for CDX2 (68.2 %). Seromucinous tumors were devoid of CDX2 expression; but all cases (except one) displayed strong and diffuse positivity with PAX8. In other words differing from mucinous tumors, seromucinous tumors show strong PAX8 positivity-similar to serous tumors. This study shows that PAX8 and CDX2 could be useful in differentiating primary mucinous from metastatic tumor. Furthermore unlike the homogeneity in seromucinous tumors for PAX8 and CDX2 mucinous tumors shows heterogeneity with different expression patterns.

  3. Decreased Expression of Beclin 1 Correlates Closely with Bcl-xL Expression and Poor Prognosis of Ovarian Carcinoma

    Science.gov (United States)

    Rao, Hui-Lan; Yang, Guo-Fen; Kung, Hsiang-Fu; Zhu, Xiao-Feng; Zeng, Yi-Xin; Cai, Mu-Yan; Xie, Dan

    2013-01-01

    Background It has been suggested that autophagy-related Beclin 1 plays a critical role in the regulation of tumor development and/or progression, but its prognostic significance and relationship with Bcl-xL expression in ovarian carcinoma are unclear. Methodology/Principal Findings In the present study, the methods of Western blotting and immunohistochemistry (IHC) were utilized to investigate the expression status of Beclin 1 and Bcl-xL in fresh ovarian tissues and paraffin-embedded epithelial ovarian tumor tissues. Decreased expression of Beclin 1 was examined by IHC in 8.3% of normal ovaries, in 15.4% of cystadenomas, in 20.0% of borderline tumors, and in 55.6% of ovarian carcinomas, respectively. In ovarian carcinomas, decreased expression of Beclin 1 was correlated closely with ascending histological grade, later pT/pN/pM status and/or advanced clinical stage (Povarian carcinoma patients (Povarian carcinoma cohort, and combined analysis further showed that the low Beclin 1/high Bcl-xL group had the lowest survival rate. Conclusions/Significance Our findings suggest that Beclin 1 expression, as examined by IHC, could be served as an additional tool in identifying ovarian carcinoma patients at risk of tumor progression, and predicting patient survival in ovarian carcinomas with increased expression of Bcl-xL. PMID:23573264

  4. Ovarian germ cell tumors with rhabdomyosarcomatous components and later development of growing teratoma syndrome: a case report

    Directory of Open Access Journals (Sweden)

    Al-Jumaily Usama

    2012-01-01

    Full Text Available Abstract Introduction Development of a sarcomatous component in a germ cell tumor is an uncommon phenomenon. Most cases reported have a grim prognosis. Growing teratoma syndrome is also an uncommon phenomenon and occurs in approximately 2% to 7% of non seminomatous germ cell tumors and should be treated surgically. Case presentation We report the case of a 12-year-old Asian girl with an ovarian mixed germ cell tumor containing a rhabdomyosarcomatous component. She was treated with a germ cell tumor chemotherapy regimen and rhabdomyosarcoma-specific chemotherapy. Towards the end of her treatment, she developed a retroperitoneal mass that was increasing in size. It was completely resected, revealing a mature teratoma, consistent with growing teratoma syndrome. She is still in complete remission approximately three years after presentation. Conclusion The presence of rhabdomyosarcoma in a germ cell tumor should be treated by a combined chemotherapy regimen (for germ cell tumor and rhabdomyosarcoma. In addition, development of a mass during or after therapy with normal serum markers should raise the possibility of growing teratoma syndrome that should be treated surgically.

  5. MV-NIS or Investigator's Choice Chemotherapy in Treating Patients With Ovarian, Fallopian, or Peritoneal Cancer

    Science.gov (United States)

    2018-04-27

    Fallopian Tube Transitional Cell Carcinoma; Malignant Ovarian Clear Cell Tumor; Malignant Ovarian Endometrioid Tumor; Malignant Ovarian Serous Tumor; Ovarian Seromucinous Carcinoma; Ovarian Transitional Cell Carcinoma; Primary Peritoneal Serous Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

  6. Impaired Th1 immunity in ovarian cancer patients is mediated by TNFR2+ Tregs within the tumor microenvironment.

    Science.gov (United States)

    Govindaraj, Chindu; Scalzo-Inguanti, Karen; Madondo, Mutsa; Hallo, Julene; Flanagan, Katie; Quinn, Michael; Plebanski, Magdalena

    2013-10-01

    Ovarian cancer is a prevalent gynecological malignancy with potent immune-suppression capabilities; regulatory T cells (Tregs) are significant contributors to this immune-suppression. As ovarian cancer patients present with high levels of TNF and Tregs expressing TNFR2 are associated with maximal suppressive capacity, we investigated TNFR2+ Tregs within these patients. Indeed, TNFR2+ Tregs from tumor-associated ascites were the most potent suppressor T cell fraction. They were abundantly present within the ascites and more suppressive than peripheral blood TNFR2+ Tregs in patients. The increased suppressive capacity can be explained by a distinct cell surface expression profile, which includes high levels of CD39, CD73, TGF-β and GARP. Additionally, CD73 expression level on TNFR2+ Tregs was inversely correlated with IFN-γ production by effector T cells. This Treg fraction can be selectively recruited into the ascites from the peripheral blood of patients. Targeting TNFR2+ Tregs may offer new approaches to enhance the poor survival rates of ovarian cancer. © 2013.

  7. Endometriosis and Ovarian Cancer: A Review of Clinical, Pathologic, and Molecular Aspects

    Science.gov (United States)

    Wei, Jian-Jun; William, Josette; Bulun, Serdar

    2014-01-01

    Summary Endometriosis is a chronic disease that affects millions of reproductive-age women. Despite the destructive and invasive nature of endometrioses, most cases are perpetually benign or eventually regress; however, atypical endometriosis is a precursor lesion and can lead to certain types of ovarian cancer. Endometriosis induced inflammation and auto- and paracrine production of sex steroid hormones contribute to ovarian tumorigenesis. These changes provide microenvironment necessary to accumulate enough genetic alterations for endometriosis associated malignant transformation. It takes years for endometriosis to undergo the pathophysiological progression that begins with atypical epithelial proliferation (atypical endometriosis and metaplasia), and then is followed by the formation of well-defined borderline tumors, and finally culminates in fully malignant ovarian cancer. This study is a review of the natural history of endometriosis and the role of microenvironments that favor the accumulation of genetic alterations and endometriosis-associated ovarian cancer progression. PMID:21979592

  8. IL-12 Expressing oncolytic herpes simplex virus promotes anti-tumor activity and immunologic control of metastatic ovarian cancer in mice.

    Science.gov (United States)

    Thomas, Eric D; Meza-Perez, Selene; Bevis, Kerri S; Randall, Troy D; Gillespie, G Yancey; Langford, Catherine; Alvarez, Ronald D

    2016-10-27

    Despite advances in surgical aggressiveness and conventional chemotherapy, ovarian cancer remains the most lethal cause of gynecologic cancer mortality; consequently there is a need for new therapeutic agents and innovative treatment paradigms for the treatment of ovarian cancer. Several studies have demonstrated that ovarian cancer is an immunogenic disease and immunotherapy represents a promising and novel approach that has not been completely evaluated in ovarian cancer. Our objective was to evaluate the anti-tumor activity of an oncolytic herpes simplex virus "armed" with murine interleukin-12 and its ability to elicit tumor-specific immune responses. We evaluated the ability of interleukin-12-expressing and control oncolytic herpes simplex virus to kill murine and human ovarian cancer cell lines in vitro. We also administered interleukin-12-expressing oncolytic herpes simplex virus to the peritoneal cavity of mice that had developed spontaneous, metastatic ovarian cancer and determined overall survival and tumor burden at 95 days. We used flow cytometry to quantify the tumor antigen-specific CD8 + T cell response in the omentum and peritoneal cavity. All ovarian cancer cell lines demonstrated susceptibility to oncolytic herpes simplex virus in vitro. Compared to controls, mice treated with interleukin-12-expressing oncolytic herpes simplex virus demonstrated a more robust tumor antigen-specific CD8 + T-cell immune response in the omentum (471.6 cells vs 33.1 cells; p = 0.02) and peritoneal cavity (962.3 cells vs 179.5 cells; p = 0.05). Compared to controls, mice treated with interleukin-12-expressing oncolytic herpes simplex virus were more likely to control ovarian cancer metastases (81.2 % vs 18.2 %; p = 0.008) and had a significantly longer overall survival (p = 0.02). Finally, five of 6 mice treated with interleukin-12-expressing oHSV had no evidence of metastatic tumor when euthanized at 6 months, compared to two of 4 mice treated with

  9. Absence of PD-L1 on tumor cells is associated with reduced MHC I expression and PD-L1 expression increases in recurrent serous ovarian cancer.

    Science.gov (United States)

    Aust, Stefanie; Felix, Sophie; Auer, Katharina; Bachmayr-Heyda, Anna; Kenner, Lukas; Dekan, Sabine; Meier, Samuel M; Gerner, Christopher; Grimm, Christoph; Pils, Dietmar

    2017-03-07

    Immune-evasion and immune checkpoints are promising new therapeutic targets for several cancer entities. In ovarian cancer, the clinical role of programmed cell death receptor ligand 1 (PD-L1) expression as mechanism to escape immune recognition has not been clarified yet. We analyzed PD-L1 expression of primary ovarian and peritoneal tumor tissues together with several other parameters (whole transcriptomes of isolated tumor cells, local and systemic immune cells, systemic cytokines and metabolites) and compared PD-L1 expression between primary tumor and tumor recurrences. All expressed major histocompatibility complex (MHC) I genes were negatively correlated to PD-L1 abundances on tumor tissues, indicating two mutually exclusive immune-evasion mechanisms in ovarian cancer: either down-regulation of T-cell mediated immunity by PD-L1 expression or silencing of self-antigen presentation by down-regulation of the MHC I complex. In our cohort and in most of published evidences in ovarian cancer, low PD-L1 expression is associated with unfavorable outcome. Differences in immune cell populations, cytokines, and metabolites strengthen this picture and suggest the existence of concurrent pathways for progression of this disease. Furthermore, recurrences showed significantly increased PD-L1 expression compared to the primary tumors, supporting trials of checkpoint inhibition in the recurrent setting.

  10. Local morphologic scale: application to segmenting tumor infiltrating lymphocytes in ovarian cancer TMAs

    Science.gov (United States)

    Janowczyk, Andrew; Chandran, Sharat; Feldman, Michael; Madabhushi, Anant

    2011-03-01

    classes based on local structural properties. In this paper, we apply LMS to the specific problem of classifying regions of interest in Ovarian Cancer (OCa) histology images as either tumor or stroma. This approach is used to classify lymphocytes as either tumor infiltrating lymphocytes (TILs) or non-TILs; the presence of TILs having been identified as an important prognostic indicator for disease outcome in patients with OCa. We present preliminary results on the tumor/stroma classification of 11,000 randomly selected locations of interest, across 11 images obtained from 6 patient studies. Using a Probabilistic Boosting Tree (PBT), our supervised classifier yielded an area under the receiver operation characteristic curve (AUC) of 0.8341 +/-0.0059 over 5 runs of randomized cross validation. The average LMS computation time at every spatial location for an image patch comprising 2000 pixels with 24 particles at every location was only 18s.

  11. Role of Estrogen and Progesterone in the Survival of Ovarian Tumors — A Study of the Human Ovarian Adenocarcinoma Cell Line OC-117-VGH

    Directory of Open Access Journals (Sweden)

    Kung-Chong Chao

    2005-08-01

    Conclusion: Based on the findings of decreased survival and/or growth in OC-117-VGH ovarian adenocarcinoma cells treated with either estrogen or progesterone, we suspect that both hormones act effectively against ER-negative and PR-negative ovarian cancer cells. These findings should lead to a reassessment of hormone therapy for ovarian cancers.

  12. Mesothelial neoplasms presenting as, and mimicking, ovarian cancer.

    Science.gov (United States)

    Mani, Haresh; Merino, Maria J

    2010-11-01

    Mesotheliomas of the abdominal cavity are rare tumors that primarily involve the peritoneum, mesentery, and omentum. The involvement of the viscera is usually secondary to bulky and extensive serosal disease. We describe 7 cases of mesothelioma in which the initial manifestation was that of an ovarian mass. All patients underwent surgery with a primary diagnosis of ovarian cancer. Clinical histories, gross features, and histology slides were reviewed. Immunostains were performed on all cases and electron microscopy was performed in 2 cases. The patients ranged in age from 22 to 52 years and the lesions ranged in size from 3.8 to 9 cm. Of the 7 cases, 4 were predominantly cystic and 3 were solid. Histologically, all cystic tumors were multicystic mesothelioma, whereas the 3 solid tumors were diffuse malignant mesotheliomas. One patient had a borderline mucinous tumor with the mesothelioma occurring as a mural nodule, an association not described earlier. The oldest patient in this series had a diffuse malignant mesothelioma of the peritoneum with predominant ovarian surface involvement. Mesothelial neoplasms can present as ovarian masses in young women. Awareness of this presentation is important to establish appropriate management.

  13. The Diagnostic Value of Transvaginal Sonograph (TVS), Color Doppler, and Serum Tumor Marker CA125, CEA, and AFP in Ovarian Cancer.

    Science.gov (United States)

    Zhang, Fang; Zhang, Zhou-Long

    2015-06-01

    The purpose of this study is to investigate the diagnostic value of transvaginal sonograph (TVS), color Doppler, and serum tumor marker CA125, CEA, and AFP in ovarian cancer. From June, 2011 to May, 2013, 102 cases with adnexal mass were recruited in this study (32 cases of malignant ovarian cancer and 70 cases of benign ovarian tumor according to pathological diagnosis). TVS, color Doppler, and serum tumor markers were used for tumor diagnosis. The sensitivity, specifity, positive prediction, negative prediction, and Youden's index were analyzed. Of the 102 patients, 32 were diagnosed with malignant ovarian cancer and 70 were diagnosed with benign ovarian tumor according to pathological diagnosis. Based on TVS results, 37 cases were malignant while 65 cases were benign. Based on color Doppler results, 34 cases were malignant while 68 cases were benign. Based on TVS and color Doppler results, 35 cases were malignant while 65 were benign. Based on CA125 test results, 34 cases were malignant while 68 cases were benign. Based on CEA test results, 8 cases were malignant and 94 cases were benign. Bases on AFP test results, 9 cases were malignant while 93 cases were benign. Based on the results of combination tumor marker test, 38 cases were malignant while 64 cases were benign. The combination of TVS, color Doppler, and tumor marker test showed optimal diagnostic value with a sensitivity of 90.63 %, specificity of 97.14 %, positive prediction of 93.94 %, negative prediction of 98.55 %, and Youden's index of 94.02 %. The combination of TVS, color Doppler, and tumor marker test is of great diagnostic value, which should be widely used in clinical practice.

  14. High efficacy of CpG-ODN, cetuximab and cisplatin combination for very advanced ovarian xenograft tumors.

    Science.gov (United States)

    Sommariva, Michele; de Cesare, Michelandrea; Meini, Alessandra; Cataldo, Alessandra; Zaffaroni, Nadia; Tagliabue, Elda; Balsari, Andrea

    2013-01-29

    To mimic clinical treatment situations in advanced human ovarian disease, we tested the efficacy of CpG-oligodeoxynucleotides (CpG-ODN), synthetic DNA sequences recognized by Toll-like receptor 9 and able to induce innate/adaptive immune responses, in combination with other possible therapeutic reagents in ovarian carcinoma ascites-bearing athymic mice. Mice injected i.p. with IGROV-1 ovarian cancer cells were treated at different stages of ascites progression for 4 weeks with CpG-ODN, alone or in combination with Bevacizumab, Polyinosinic:Polycytidylic acid (Poly(I):Poly(C)), Gefitinib, Cetuximab and Cisplatin. Median survival time (MST) was calculated for each group. IGROV-1 cells treated or not with Cetuximab were assayed for antibody-dependent cellular cytotoxicity by 51Cr-release assay, and for macrophage antibody-dependent cell-mediated phagocytosis by flow cytometry. In mice treated when ascitic fluid began to accumulate, CpG-ODN combined with Bevacizumab, Poly(I):Poly(C) or Gefitinib did not significantly increase MST as compared with that using CpG-ODN alone, whereas MST in mice treated with CpG-ODN plus Cetuximab was significantly increased (>103 days for combination vs 62 days for CpG alone; P = 0.0008), with 4/8 mice alive at the end of the experiment. In experiments in mice showing increased abdominal volume and body weight (27.9 ± 0.8 g after vs 23 ± 1.1 g before tumor cell injection), treatment with Cisplatin in addition to CpG-ODN/Cetuximab led to significantly increased MST (105.5 days; P = 0.001), with all mice still alive at 85 days, over that using CpG-ODN/Cetuximab (66 days), Cetuximab/Cisplatin (18.5 days), Cisplatin (23 days) or saline (16 days). At a very advanced stage of disease (body weight: 31.4 ± 0.9 g), when more than half of control mice had to be sacrificed 6 days after starting treatments, the triple-combination therapy still increased MST (45 days; P = 0.0089) vs controls. CpG-ODN combination therapies

  15. Spectrum of Childhood and Adolescent Ovarian Tumors in India: 25 Years Experience at a Single Institution

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    Ruchi Rathore

    2016-09-01

    Full Text Available BACKGROUND: Ovarian tumour in children and adolescent girls form an uncommon but important part of gynaecological malignancies. They account for 1% of all the childhood malignancies and 8% of all abdominal tumours in children. Since the ovarian cysts are thought to arise from mature follicles, these tumours were considered to be infrequent in the paediatric population. AIM: The rarity of this condition prompted us to conduct this study and share our experience on the incidence and clinicopathological features of different ovarian tumours in girls up to 20 years of age observed in last 25 years at a single tertiary care hospital. MATERIAL AND METHODS: This was a retrospective study conducted in the Department of Pathology at a tertiary hospital, Delhi. All ovarian tumours up to the age of 20 years in the past 25 years (1990-2014 were included for the purpose of studying the clinicopathological aspects of ovarian tumours in this age group. Descriptive statistics for prevalence and age-wise prevalence was done. Chi-square test, to find an association between the age, laterality and size with malignancy was performed. RESULTS: We received a total of 1102 cases of ovarian tumours over the period of 25 years  (1990 to 2014, of which 112 (10% cases were seen in girls up to 20 years of age. The mean age of the patients was 15.3 ± 4 years. The most common presenting complaint was pain abdomen (46.4 % There was a statistically significant correlation found between size and malignancy status of tumours in our study (p = 0.00. Of 112 cases of ovarian tumours, 39/112 (34.8% were malignant and 73/112 (65.2% were benign. Mature  cystic teratoma (27.6% was the most common type of benign tumour in this age group and immature teratomas were the most common type of malignant ovarian neoplasms. CONCLUSION: Premenarchal girls with ovarian masses may have varied presentations. Abdominal pain is the most common presenting complaint of young adolescent girls with

  16. Spectrum of Childhood and Adolescent Ovarian Tumors in India: 25 Years Experience at a Single Institution.

    Science.gov (United States)

    Rathore, Ruchi; Sharma, Sonal; Arora, Deepshikha

    2016-12-15

    Ovarian tumour in children and adolescent girls form an uncommon but important part of gynaecological malignancies. They account for 1% of all the childhood malignancies and 8% of all abdominal tumours in children. Since the ovarian cysts are thought to arise from mature follicles, these tumours were considered to be infrequent in the paediatric population. The rarity of this condition prompted us to conduct this study and share our experience on the incidence and clinicopathological features of different ovarian tumours in girls up to 20 years of age observed in last 25 years at a single tertiary care hospital. This was a retrospective study conducted in the Department of Pathology at a tertiary hospital, Delhi. All ovarian tumours up to the age of 20 years in the past 25 years (1990-2014) were included for the purpose of studying the clinicopathological aspects of ovarian tumours in this age group. Descriptive statistics for prevalence and age-wise prevalence was done. Chi-square test, to find an association between the age, laterality and size with malignancy was performed. We received a total of 1102 cases of ovarian tumours over the period of 25 years (1990 to 2014), of which 112 (10%) cases were seen in girls up to 20 years of age. The mean age of the patients was 15.3 ± 4 years. The most common presenting complaint was pain abdomen (46.4 %) There was a statistically significant correlation found between size and malignancy status of tumours in our study (p = 0.00). Of 112 cases of ovarian tumours, 39/112 (34.8%) were malignant and 73/112 (65.2%) were benign. Mature cystic teratoma (27.6%) was the most common type of benign tumour in this age group and immature teratomas were the most common type of malignant ovarian neoplasms. Premenarchal girls with ovarian masses may have varied presentations. Abdominal pain is the most common presenting complaint of young adolescent girls with adnexal masses. So the index of suspicion should be kept high and prompt

  17. Use of up-to-date ultrasound technologies in the diagnosis of metastatic ovarian tumors in gastric cancer

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    M. A. Chekalova

    2016-01-01

    Full Text Available We analyzed the results of ultrasound and postoperative histological studies of 14 patients with primary diagnosis of gastric cancer who received treatment at the cancer research center in 2014. Metastases to the ovaries detected in all cases with disseminated gastric cancer as the primary diagnosis, and in monitoring the effectiveness of treatment. The most characteristic ultrasound signs of metastatic ovarian tumors. When elastography in all cases, metastatic the affected ovaries were determined in the solid sections of the component of high-density (stiffness, charterhouses type 5 (blue, the average rigidity coefficient was 10.2–32.2. Solid-cystic masses in cases of tumor were mapped to 4 of Krukenberg type (which met as the dense and elastic stretches, charterhouses blue and green colors.

  18. Ganoderma lucidum exerts anti-tumor effects on ovarian cancer cells and enhances their sensitivity to cisplatin.

    Science.gov (United States)

    Zhao, Sufen; Ye, Gang; Fu, Guodong; Cheng, Jian-Xin; Yang, Burton B; Peng, Chun

    2011-05-01

    Ganoderma lucidum is a herbal mushroom known to have many health benefits, including the inhibition of tumor cell growth. However, the effect of Ganoderma lucidum on epithelial ovarian cancer (EOC), the most fatal gynecological malignancy, has not yet been reported. In this study, we determined whether Ganoderma lucidum regulates EOC cell activity. Using several cell lines derived from EOC, we found that Ganoderma lucidum strongly decreased cell numbers in a dose-dependent manner. Ganoderma lucidum also inhibited colony formation, cell migration and spheroid formation. In particular, Ganoderma lucidum was effective in inhibiting cell growth in both chemosensitive and chemoresistant cells and the treatment with Ganoderma lucidum significantly enhanced the effect of cisplatin on EOC cells. Furthermore, Ganoderma lucidum induced cell cycle arrest at the G2/M phase and also induced apoptosis by activating caspase 3. Finally, Ganoderma lucidum increased p53 but inhibited Akt expression. Taken together, these findings suggest that Ganoderma lucidum exerts multiple anti-tumor effects on ovarian cancer cells and can enhance the sensitivity of EOC cells to cisplatin.

  19. Assessment of Ovarian Cancer Tumors Treated with Intraperitoneal Cisplatin Therapy by Nanoscopic X-ray Fluorescence Imaging

    Science.gov (United States)

    Laforce, Brecht; Carlier, Charlotte; Vekemans, Bart; Villanova, Julie; Tucoulou, Rémi; Ceelen, Wim; Vincze, Laszlo

    2016-07-01

    Ovarian cancer is amongst the most common types of cancer in women, with a relatively low overall cure rate of approximately 30%. This is therefore an important incentive to urge for further research in order to maximize the chances of survival for these patients. Intraperitoneal chemotherapy with Cisplatin is an effective treatement for ovarian cancer; however, many questions still remain concerning the ideal treatment protocol and tumor resistance towards the drug, which should be resolved for optimal application of this therapy. For the first time in-vivo grown tumors treated with both hyper- and normothermic intraperitoneal chemotherapy have been studied using nano-XRF spectroscopy to examine the platinum (Pt) distribution within the analyzed tissues. These measurements prove Pt resides predominantly outsides the cancer cells in the stroma of the tissue. These findings indicate the resistance mechanism of the cancer cells prevents Cisplatin from diffusing through their cell membranes. This is an important addition to the existing knowledge on the resistance mechanism providing insights which might help to overcome this effect. In our aim to find the optimal treatment protocol, no significant differences were found between the two examined procedures. A more extensive data set will be needed to draw definite conclusions.

  20. Relevance of HLA-DP/DQ and ICAM-1 SNPs among Ovarian Cancer Patients.

    Science.gov (United States)

    Ghazy, Amany A; El-Etreby, Nour M

    2016-01-01

    Ovarian cancer is one of the most lethal gynecological malignancies and the fifth leading cause of cancer deaths among women. The high mortality rate is largely attributed to its diagnosis in advanced stages. Poor prognosis of ovarian cancer is usually due to the lack of specific or effective screening and diagnostic methods for identifying early-stage disease. Our study aimed to study the role of HLA-DP, HLA-DQ, and ICAM-1 SNPs in diagnosis and/or prognosis of ovarian tumors. The current study was conducted on 60 patients with ovarian tumors (benign, borderline, and malignant) and 20 healthy volunteers. Genotyping of HLA-DP rs3077, HLA-DQ rs3920, and ICAM-1 rs1437 SNPs was done using 5' nuclease assay. We found significant association of HLA-DP rs3077 AA, HLA-DQ rs3920 GG, ICAM-1 rs1437 CC, and CT genotypes with increased risk of ovarian cancer (OR = 43.5, 6, 25, and 2.6, respectively). In addition, HLA-DQ rs3920 and ICAM-1 rs1437 alleles vary significantly among different types of ovarian cancer (P = 0.003 and 0.001, respectively). HLA-DP rs3077, HLA-DQ rs3920, and ICAM-1 rs1437 SNPs could help in the diagnosis and prognosis of ovarian cancer.

  1. Ovarian cancer treatment with a tumor-targeting and gene expression-controllable lipoplex

    OpenAIRE

    He, Zhi-Yao; Deng, Feng; Wei, Xia-Wei; Ma, Cui-Cui; Luo, Min; Zhang, Ping; Sang, Ya-Xiong; Liang, Xiao; Liu, Li; Qin, Han-Xiao; Shen, Ya-Li; Liu, Ting; Liu, Yan-Tong; Wang, Wei; Wen, Yan-Jun

    2016-01-01

    Overexpression of folate receptor alpha (FR?) and high telomerase activity are considered to be the characteristics of ovarian cancers. In this study, we developed FR?-targeted lipoplexes loaded with an hTERT promoter-regulated plasmid that encodes a matrix protein (MP) of the vesicular stomatitis virus, F-LP/pMP(2.5), for application in ovarian cancer treatment. We first characterized the pharmaceutical properties of F-LP/pMP(2.5). The efficient expression of the MP-driven hTERT promoter in ...

  2. SMARCA4 (BRG1) loss of expression is a useful marker for the diagnosis of ovarian small cell carcinoma of the hypercalcemic type (ovarian rhabdoid tumor): a comprehensive analysis of 116 rare gynecologic tumors, 9 soft tissue tumors, and 9 melanomas.

    Science.gov (United States)

    Karanian-Philippe, Marie; Velasco, Valérie; Longy, Michel; Floquet, Anne; Arnould, Laurent; Coindre, Jean-Michel; Le Naoures-Méar, Cécile; Averous, Gerlinde; Guyon, Frédéric; MacGrogan, Gaëtan; Croce, Sabrina

    2015-09-01

    Ovarian small cell carcinoma of the hypercalcemic type (SCCOHT)/ovarian rhabdoid tumor is a rare and highly malignant tumor that typically occurs in young women. Up until now the diagnosis has been made on the basis of morphology without any specific immunohistochemical (IHC) markers. However, several authors have shown recently that SCCOHTs are characterized by inactivation of the SMARCA4 gene (encoding the BRG1 protein) resulting in a loss of BRG1 protein expression in IHC. We evaluated BRG1 and INI1 expression in 12 SCCOHTs and in a series of 122 tumors that could mimic SCCOHT morphologically: 9 juvenile granulosa cell tumors, 47 adult granulosa cell tumors, 33 high-grade ovarian serous carcinomas, 9 desmoplastic round cell tumors, 13 Ewing sarcomas (5 from the pelvis and 8 from soft tissues), 1 round cell sarcoma associated with CIC-DUX4 translocation from soft tissue (thigh), 1 case of high-grade endometrial stromal sarcoma of the ovary, and 9 melanomas. Forty-four adult granulosa cell tumors were interpretable by IHC. All 12 SCCOHTs were devoid of BRG1 expression and expressed INI1. All other interpretable 119 tumors showed BRG1 nuclear positivity, with variable staining proportions, ranging from 10% to 100% of positive cells (mean: 77%, median: 80%), variable intensities (weak: 5%, moderate: 37%, strong: 58%), and distributions: diffuse in 82 cases (70%) and heterogenous in 36 cases (30%). BRG1 positivity was heterogenous in desmoplastic round cell tumors and adult granulosa cell tumors. Overall, BRG1 is a useful diagnostic marker in SCCOHT, showing the absence of expression in SCCOHT. Nevertheless, the possible heterogeneity and the variable intensity of this staining warrant caution in the interpretation of BRG1 staining in biopsy specimens.

  3. Effect of DC-CIK treatment on tumor markers and T cell subsets in patients with advanced ovarian cancer

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    Jie-Qun Guo

    2016-10-01

    Full Text Available Objective: To investigate the effects of dendritic cells (DC and cytokine induced killer cells (CIK on tumor markers and T cell subsets in peripheral blood of patients with advanced ovarian cancer. Methods: A total of 100 cases of patients with advanced ovarian cancer who were proved by operation and pathology in the department of gynecologic oncology in our hospital were selected from April 2013 to April 20l6, and randomly divided into experimental group and control group, the control group was treated with TC (Taxinol+Cisplat chemotherapy alone, the experimental group was treated with DC-CIK combined with chemotherapy. Before and after treatment, the changes of CD3+, CD4+, CD8+, CD4+/CD8+, CD4+/CD25+, NK cells in peripheral blood and serum tumor markers (CA125, CA19-9, HE4 were detected. Results: Before treatment, the phenotypes of T cell subsets in the two groups were not significantly different; in the experimental group after treatment, the levels of CD3+, CD4+, CD4+/CD8+, and NK cells were increased,while the levels of CD4+/CD25+ and CD8+ were decreased, compared with before treatment, the differences were statistically significant; the phenotype changes of T cells were not statistically significant before and after treatment in the control group; after treatment, there were significant differences in the levels of CD4+, CD8+, CD4+/CD8+, CD4+/CD25+ and NK cells between the two groups. Before treatment, there were no significant differences in HE4 value, CA125 value and CA19-9 value between the two groups; after treatment, the tumor markers in the two groups were all decreased, and the difference was significant as compared with those before treatment; after treatment, the CA125 value, CA19-9 value and HE4 value were (73.68±79.46 U/mL, (54.32±32.85 U/mL and (69.57±39.85 pmol/L respectively, the values of three tumor markers were compared with the control group, with a statistical difference. Conclusion: DC-CIK treatment can improve the

  4. Quantification analysis of the expression of tumor-associated proteins in serum samples from patients with ovarian cancer and those with other tumor location. Possibilities of their use in the diagnosis and estimation of the extent of a tumorous process

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    T. S. Bobrova

    2012-01-01

    Full Text Available The specific features of the expression of tumor-associated proteins (TAP were immunologically studied in the sera of patients with ovarian cancer (OC and other tumor location by means of immune sera (As or monoclonal antibodies (MAb to find out whether they could be used to diagnose and estimate the extent of a tumorous process.MAb 1 (to HEp-2 cell membrane proteins, larynx cancer, Ac4 (to a pool of two ovarian cystadenocarcinomas, and MAb 3 (to affinity-pu- rified proteins of the apparently intact human gastric mucosa were used to examine the sera of patients with OC and other tumor location and positive responsiveness was detected in 82, ~100, and 77 % of cases, respectively. The differences in the expression of TAP in the patients versus healthy donors were shown to be statistically significant (p = 0.0001; p = 0.015; p = 0.01, respectively.The sensitivity of quantifying ELISA in detecting TAP was 78 and 85 % in patients with Stages I–II and III–IV OC, respectively; ~100 and 89 % in patients with breast cancer and in those with gastrointestinal tract cancer, respectively; and 60 and 14 % in patients with lymphopro- liferative diseases and healthy donors, respectively. Comparison of TAP detection rates in the authors’ test systems with multiplex testing with a biochip array of 12 tumor markers has shown that these test systems are at the world standard level.

  5. Precocious puberty secondary to a mixed germ cell-sex cord-stromal tumor associated with an ovarian yolk sac tumor: a case report

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    Metwalley Kotb

    2012-06-01

    Full Text Available Abstract Introduction Ovarian tumors are the least common cause of sexual precocity in girls. Mixed germ cell-sex cord-stromal tumors associated with a yolk sac tumor of the ovary are rare neoplasms, of which only a small number of well-documented cases have been described so far. Here, we report precocious puberty in a four-year-old Egyptian girl caused by a mixed germ cell-sex cord-stromal tumor associated with a yolk sac tumor of the ovary. Case presentation A four-year-old Egyptian girl was referred to our pediatric endocrinology unit for evaluation of bilateral breast budding, pubic hair and vaginal bleeding. On examination, we found that her breast enlargement and pubic hair were compatible with Tanner III. A thorough workup revealed a large mass in her right ovary. Magnetic resonance imaging ofher brain showed that her pituitary gland was normal. A hormonal assay revealed high levels of estradiol, 280 to 375pmol/L; progesterone, 5.3 nmol/L; testosterone 38.9 pg/mL; and androstenedione, 4.1 ng/mL. Her basal and stimulated levels of luteinizing hormone and follicle-stimulating hormone were low. Tumor markers levels were high, with a total inhibin of 1,069U/L and an alpha-fetoprotein of 987 μg/L. Her chromosomes were normal (46XX. Our patient underwent an explorative laparotomy and a solid tumor localized to her right ovary was identified. A right salpingo-oophorectomy was performed and the histopathological diagnosis was a mixed germ cell-sex cord-stromal tumorwith a yolk sac tumor of the ovary. Postoperatively, she was started on treatment with chemotherapy. Our patient is doing well without evidence of tumor recurrence or metastasis during eight months of postoperative follow-up. Conclusion Although a mixed germ cell-sex cord-stromal tumor associated with a yolk sac tumor of the ovary is a rare occurrence, it should be considered in the differential diagnosis for a prepubescent girl with an abdominal mass and precocious puberty.

  6. CYTOGENETICS, PLOIDY AND DIFFERENTIATION OF HUMAN TESTICULAR, OVARIAN AND EXTRAGONADAL GERM-CELL TUMORS

    NARCIS (Netherlands)

    OOSTERHUIS, JW; CASTEDO, SMMJ; DEJONG, B

    1990-01-01

    Data from cytogenetics of testicular, ovarian and extragonadal germ cell tumours indicate that the group of germ cell tumours for which Skakkebaek proposed the name gonocytoma (seminoma, dysgerminoma and germinoma) is characterized by the presence of isochromosome 12p. The (dysplastic) gonocytes

  7. Struma Ovarii, A Rare Form of Ovarian Tumor: Clinical Analysis of 6 Cases

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    Kazım Gezginç

    2011-08-01

    CONCLUSION: Struma ovarii is a medical rarity and preoperative diagnosis is generally impossible. The diagnosis was confirmed only by pathologic findings. Clinicians should be aware of this diagnosis and include it in the differential diagnosis when a patient presents with signs and symptoms of ovarian malignancy.

  8. Expression of GLUT-1 in epithelial ovarian carcinoma: correlation with tumor cell proliferation, angiogenesis, survival and ability to predict optimal cytoreduction.

    Science.gov (United States)

    Semaan, Assaad; Munkarah, Adnan R; Arabi, Haitham; Bandyopadhyay, Sudeshna; Seward, Shelly; Kumar, Sanjeev; Qazi, Aamer; Hussein, Yasser; Morris, Robert T; Ali-Fehmi, Rouba

    2011-04-01

    GLUT-1 is involved at various steps in the processes of tumor progression. The objective of this study was to examine the relationship between GLUT-1 expression and tumor proliferation and angiogenesis in epithelial ovarian carcinoma. Specimens from 213 patients with epithelial ovarian carcinoma were evaluated by immunohistochemistry for GLUT-1, Ki-67, and vascular endothelial growth factor. Tumor microvessel density was assessed with CD34 immunostaining. We investigated the relationships between GLUT-1 expression and clinicopathologic characteristics, tumor angiogenesis (tumor MVD and vascular endothelial growth factor expression), and tumor proliferation (Ki-67). The effect of GLUT-1 expression on patient survival and on the volume of residual disease after cytoreduction was determined. There was a significant positive correlation between expression of GLUT-1, Ki-67, and microvessel density. In univariate survival analysis, high GLUT-1 expression, high Ki-67 expression and high tumor microvessel density showed a significant impact on patient survival (p=0.0001). In multivariate analysis including patients with all tumor stages, after controlling for age, race, stage, grade, MVD, and the 3 markers (GLUT-1, Ki-67 and VEGF), only age (HR 1.5; 95% CI 1-2.3), stage (HR 3.6; 95% CI 1.8-7.5) and grade (HR 2.3; 95% CI 1.2-4.5) retained their significance as independent poor prognostic factors. Tumors simultaneously overexpressing GLUT-1 and Ki-67 were less likely to be optimally cytoreduced as compared to tumors overexpressing only one or neither of those two markers (OR: 3.8, p=0.01). Expression of GLUT-1 correlates with tumor proliferation and microvessel density in epithelial ovarian carcinoma. In addition, patients with rapidly proliferating advanced stage tumors overexpressing GLUT-1 have a lesser chance for optimal cytoreduction. Copyright © 2010 Elsevier Inc. All rights reserved.

  9. A new method for isolation of interstitial fluid from human solid tumors applied to proteomic analysis of ovarian carcinoma tissue.

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    Hanne Haslene-Hox

    Full Text Available Major efforts have been invested in the identification of cancer biomarkers in plasma, but the extraordinary dynamic range in protein composition, and the dilution of disease specific proteins make discovery in plasma challenging. Focus is shifting towards using proximal fluids for biomarker discovery, but methods to verify the isolated sample's origin are missing. We therefore aimed to develop a technique to search for potential candidate proteins in the proximal proteome, i.e. in the tumor interstitial fluid, since the biomarkers are likely to be excreted or derive from the tumor microenvironment. Since tumor interstitial fluid is not readily accessible, we applied a centrifugation method developed in experimental animals and asked whether interstitial fluid from human tissue could be isolated, using ovarian carcinoma as a model. Exposure of extirpated tissue to 106 g enabled tumor fluid isolation. The fluid was verified as interstitial by an isolated fluid:plasma ratio not significantly different from 1.0 for both creatinine and Na(+, two substances predominantly present in interstitial fluid. The isolated fluid had a colloid osmotic pressure 79% of that in plasma, suggesting that there was some sieving of proteins at the capillary wall. Using a proteomic approach we detected 769 proteins in the isolated interstitial fluid, sixfold higher than in patient plasma. We conclude that the isolated fluid represents undiluted interstitial fluid and thus a subproteome with high concentration of locally secreted proteins that may be detected in plasma for diagnostic, therapeutic and prognostic monitoring by targeted methods.

  10. MiR-23b targets cyclin G1 and suppresses ovarian cancer tumorigenesis and progression.

    Science.gov (United States)

    Yan, Jing; Jiang, Jing-yi; Meng, Xiao-Na; Xiu, Yin-Ling; Zong, Zhi-Hong

    2016-02-13

    It has been proposed that cyclin G1 (CCNG1) participates in p53-dependent G1-S and G2 checkpoints and might function as an oncogenic protein in the initiation and metastasis of ovarian carcinoma. MicroRNA 23b (miR-23b) is a critical regulatory factor in the progression of many cancer cell types that targets the relevant genes. MiR-23b expression in ovarian tissues was quantified by quantitative reverse transcription-PCR. The ovarian cancer cell lines OVCAR3, HO8910-PM, and SKOV3/DDP were transfected with miR-23b, after we assayed the cell phenotype and expression of the relevant molecules. Dual-luciferase reporter assay and a xenograft mouse model were used to examine the expression of miR-23b and its target gene CCNG1. MIR23B mRNA expression was significantly lower in epithelial ovarian carcinoma and borderline tumors than in normal ovarian tissues and benign tumors, and miR-23b expression among ages and pathological subtypes was significantly different. CCNG1 mRNA expression was significantly lower in normal ovarian tissues than in benign tumors, borderline tumors, and ovarian carcinomas, and expression among pathological subtypes was significantly different. MiR-23b overexpression inhibited ovarian cancer cell proliferation, invasion, and migration, and induced apoptosis. Dual-luciferase reporter assay showed that miR-23b bound with the 3' untranslated region of CCNG1. MiR-23b overexpression significantly downregulated CCNG1, urokinase, survivin, Bcl-xL, P70S6K, and matrix metallopeptidase-9 (MMP9) mRNA and protein expression. Furthermore, miR-23b inhibited tumor growth and suppressed CCNG1 expression in vitro. Our findings show that miR-23b may inhibit ovarian cancer tumorigenesis and progression by downregulating CCNG1 and the expression of the relevant genes. MiR-23b is a potentially novel application for regulating ovarian carcinoma progression.

  11. Expression of preoperative KISS1 gene in tumor tissue with epithelial ovarian cancer and its prognostic value.

    Science.gov (United States)

    Cao, Fang; Chen, Liping; Liu, Manhua; Lin, Weiwei; Ji, Jinlong; You, Jun; Qiao, Fenghai; Liu, Hongbin

    2016-11-01

    Our study aimed to elucidate the role of Kisspeptin (KISS1) in tumor tissues of patients with epithelial ovarian cancer (EOC) and investigate the prognostic value of this biomarker.Forty EOC patients and 20 uterine fibroids female patients with healthy ovaries undergoing cytoreductive surgery between January 2010 and January 2014 in our hospital were enrolled in this study. KISS1 expression in tumor and normal tissues was detected. Correlations between clinic-pathologic variables and KISS1 expression in EOC tissues and the prognostic value of KISS1 for overall survival were evaluated.During the follow-up of 11.2 to 62.1 months, the overall survival rate and mean survival time were 28.9% (11/38) and 38.35 ± 2.84 months. Preoperative KISS1 mRNA was higher in tumor tissue than in normal tissue (P <0.001), and it was associated with histologic grade of tumor, surgical FIGO stage, metastasis, and residual tumor size (all P <0.05). Multivariate survival analysis indicated significant influence of residual tumor size (HR = 2.357, P = 0.039) and preoperative KISS1 mRNA (HR = 0.0001, P <0.001) on mean survival time. Patients with low KISS1 mRNA expression had shorter survival time than those with high expression (P = 0.001).Preoperative KISS1 mRNA was a potential prognostic biomarker for EOC, and high preoperative KISS1 expression indicated a favorable prognosis.

  12. Borderline Personality Disorder: Psychotherapy

    Science.gov (United States)

    Search About Us Borderline Personality Disorder (BPD) Diagnosis and Treatment Resources For Professionals Contact Us NYP.org Borderline Personality Disorder Resource Center Diagnosis and Treatment Psychotherapy ...

  13. Diagnostic value of preoperative SUVmax on FDG-PET/CT for the detection of ovarian cancer.

    Science.gov (United States)

    Tanizaki, Yuko; Kobayashi, Aya; Shiro, Michihisa; Ota, Nami; Takano, Rei; Mabuchi, Yasushi; Yagi, Shigetaka; Minami, Sawako; Terada, Masaki; Ino, Kazuhiko

    2014-03-01

    The objective of this study was to investigate the preoperative diagnostic value of F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography and computed tomography (PET/CT) in patients with ovarian cancer. One hundred sixty patients suspected of having malignant ovarian tumors were included in this study. All patients underwent FDG-PET/CT scans before operation, and the maximum standardized uptake value (SUVmax) of the primary tumor was measured. We evaluated the diagnostic accuracy of SUVmax for detecting malignancy and its relationship with histological findings. Postoperative pathological diagnoses showed that 67 were malignant, 14 were borderline malignant, and 79 were benign tumors. With the use of a cutoff SUVmax of 2.9 obtained from the receiver operating characteristic curve analysis, the sensitivity, specificity, positive predictive value, and negative predictive value for detecting malignancy were 80.6%, 94.6%, 91.5%, and 87.1%, respectively. Positive FDG accumulation (SUVmax ≥ 2.9) was shown in 89.5% of serous adenocarcinoma and in 92.3% of endometrioid adenocarcinoma. In contrast, lower frequencies of positive FDG accumulation were shown in clear cell adenocarcinoma (54.5%), mucinous adenocarcinoma (66.7%), and metastatic carcinoma (66.7%), and the median SUVmax of these 3 histological types were significantly lower than those of serous and endometrioid types. In addition, a positive FDG accumulation was shown in all patients with malignant transformation of mature cystic teratoma. Finally, of the 14 borderline malignant tumors, only 2 (14.3%) showed positive FDG accumulation. The SUVmax on FDG-PET/CT is useful for differentiating ovarian cancer from borderline or benign tumor with a high specificity and positive predictive value. However, our data also demonstrated a lower FDG uptake value in clear cell or mucinous histological finding, suggesting that SUVmax may vary depending on the tumor histological subtype.

  14. Mutations of the CHK2 gene are found in some osteosarcomas, but are rare in breast, lung, and ovarian tumors.

    Science.gov (United States)

    Miller, Carl W; Ikezoe, Takayuki; Krug, Utz; Hofmann, Wolf-K; Tavor, Sigal; Vegesna, Vijaya; Tsukasaki, Kunihiro; Takeuchi, Seisho; Koeffler, H Phillip

    2002-01-01

    Checkpoint genes, activated in response to DNA damage and other stresses, are frequently targeted for alteration in cancer. Checkpoint kinase 2 (CHK2, CDS1, RAD53) is activated by ataxia telangiectasia mutated (ATM) in response to gamma irradiation. Activated CHK2 stabilizes TP53, and acts on other cell cycle and stress regulators. These findings place CHK2 in the middle of a pathway frequently targeted in cancer. Because of this, and the observation that CHK2 mutations are inherited in some Li-Fraumeni cancer syndrome families, we decided to examine the role of CHK2 mutations in sporadic cancers. Exploiting the genomic sequence of chromosome 22, we looked for mutations in the exons and intron junctions of the CHK2 gene in DNA samples from 170 patients (57 osteosarcomas, 25 other sarcomas, 35 nonsmall-cell lung, 20 ovarian, and 33 breast cancers). Missense mutations affecting the forkhead and kinase domains were detected in four osteosarcomas and in one ovarian and one lung cancer. These findings of CHK2 gene mutations are consistent with osteosarcoma being a defining tumor of Li-Fraumeni syndrome. The occurrence of CHK2 mutations in sporadic cancers emphasizes the importance of the stress pathway which includes TP53.

  15. Proapoptotic protein Smac mediates apoptosis in cisplatin-resistant ovarian cancer cells when treated with the anti-tumor agent AT101.

    Science.gov (United States)

    Hu, Wenbin; Wang, Fang; Tang, Jingsheng; Liu, Xinyu; Yuan, Zhu; Nie, Chunlai; Wei, Yuquan

    2012-01-02

    Chemoresistance of ovarian cancer has been previously attributed to the expression and activation of Bcl-2 family proteins. BH3-mimetic molecules possessing potential anticancer activity are able to inhibit antiapoptotic Bcl-2 family proteins. AT101 (R-(-)-gossypol), a natural BH3-mimetic molecule, has shown anti-tumor activity as a single agent and in combination with standard anticancer therapies in a variety of tumor models. Here, we report the effect of AT101 on apoptosis in cisplatin-resistant ovarian cancer cells and identify the major molecular events that determine sensitivity. AT101 induced cell apoptosis by activating Bax through a conformational change, translocation, and oligomerization. The inhibition of Bax expression only partially prevented caspase-3 cleavage. However, the gene silencing of Bax had no effect on mitochondrial Smac release. Further experiments demonstrated that Smac reduction inhibited caspase-3 activation and attenuated cell apoptosis. More importantly, the inhibition of Smac or overexpression of XIAP attenuated Bax activation in ovarian cells. Furthermore, our data indicate that the Akt-p53 pathway is involved in the regulation of Smac release. Taken together, our data demonstrate the role of Smac and the molecular mechanisms of AT101-induced apoptosis of chemoresistant ovarian cancer cells. Our findings suggest that AT101 not only triggers Bax activation but also induces mitochondrial Smac release. Activated Smac can enhance Bax-mediated cellular apoptosis. Therefore, Smac mediates Bax activation to determine the threshold for overcoming cisplatin resistance in ovarian cancer cells.

  16. Proapoptotic Protein Smac Mediates Apoptosis in Cisplatin-resistant Ovarian Cancer Cells When Treated with the Anti-tumor Agent AT101*

    Science.gov (United States)

    Hu, Wenbin; Wang, Fang; Tang, Jingsheng; Liu, Xinyu; Yuan, Zhu; Nie, Chunlai; Wei, Yuquan

    2012-01-01

    Chemoresistance of ovarian cancer has been previously attributed to the expression and activation of Bcl-2 family proteins. BH3-mimetic molecules possessing potential anticancer activity are able to inhibit antiapoptotic Bcl-2 family proteins. AT101 (R-(−)-gossypol), a natural BH3-mimetic molecule, has shown anti-tumor activity as a single agent and in combination with standard anticancer therapies in a variety of tumor models. Here, we report the effect of AT101 on apoptosis in cisplatin-resistant ovarian cancer cells and identify the major molecular events that determine sensitivity. AT101 induced cell apoptosis by activating Bax through a conformational change, translocation, and oligomerization. The inhibition of Bax expression only partially prevented caspase-3 cleavage. However, the gene silencing of Bax had no effect on mitochondrial Smac release. Further experiments demonstrated that Smac reduction inhibited caspase-3 activation and attenuated cell apoptosis. More importantly, the inhibition of Smac or overexpression of XIAP attenuated Bax activation in ovarian cells. Furthermore, our data indicate that the Akt-p53 pathway is involved in the regulation of Smac release. Taken together, our data demonstrate the role of Smac and the molecular mechanisms of AT101-induced apoptosis of chemoresistant ovarian cancer cells. Our findings suggest that AT101 not only triggers Bax activation but also induces mitochondrial Smac release. Activated Smac can enhance Bax-mediated cellular apoptosis. Therefore, Smac mediates Bax activation to determine the threshold for overcoming cisplatin resistance in ovarian cancer cells. PMID:22052903

  17. [Ovarian tumor in a koi carp (Cyprinus carpio): Diagnosis, surgery, postoperative care and tumour classification].

    Science.gov (United States)

    Lewisch, E; Reifinger, M; Schmidt, P; El-Matbouli, M

    2014-01-01

    Although ovarian tumour in the koi (Cyprinus carpio) does not appear to be an uncommon condition, its occurrence and therapy has rarely been reported. In the present case, the decision for surgery was based on clinical and sonographic findings of an intracoelomic mass. We used tricaine methansulfonate for the anaesthesia. Laparotomy was performed by ventral access and an ovarian tumour of 12-cm diameter was removed. The wound was sutured in two layers using Vicryl®. In addition to the application of an analgesic, an antibiotic and vitamins, the postoperative conditions the patient was kept under were adapted to support wound healing. The fish recovered uneventfully and was clinically healthy during the 16-month observation period. Based on the histological findings, the tumour was diagnosed as a thecoma. Investigations using antibodies against vimentin, cytokeratin, S 100 and glial fibrillary acidic protein (GFAP) failed to provide reliable results.

  18. In vivo VEGF imaging with radiolabeled bevacizumab in a human ovarian tumor xenograft

    NARCIS (Netherlands)

    Nagengast, Wouter B.; Hospers, Geke A.; Mulder, Nanno H.; de Jong, Johan R.; Hollema, Harry; Brouwers, Adrienne H.; van Dongen, Guns A.; Perk, Lars R.; Lub-de Hooge, Marjolijn N.

    Vascular endothelial growth factor (VEGF), released by tumor cells, is an important growth factor in tumor angiogenesis. The humanized monoclonal antibody bevacizumab blocks VEGF-induced tumor angiogenesis by binding, thereby neutralizing VEGF. Our aim was to develop radiolabeled bevacizumab for

  19. Early Detection of Ovarian Cancer by Tumor Epithelium-Targeted Molecular Ultrasound

    Science.gov (United States)

    2014-10-01

    infections during pregnancy. According to our hypothesis group B streptococcus (GBS) induced maternal immune activation plays a role in placental lesions...Support: DOD ovarian cancer pilot award # W81XWH-12-1-0460. G-14 Chorioamnionitis induced by inactivated group B streptococcus : from placental lesions to...should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of

  20. Cleaved forms of the urokinase plasminogen activator receptor in plasma have diagnostic potential and predict postoperative survival in patients with ovarian cancer

    DEFF Research Database (Denmark)

    Henic, E.; Borgfeldt, C.; Christensen, I.J.

    2008-01-01

    -FIA 3 measuring the liberated uPAR(I). Tumors were classified as benign (n = 211), borderline (possibly malignant; n = 30), and well (n = 19), moderately (n = 15), and poorly (n = 60) differentiated malignant. RESULTS: All uPAR forms as well as CA125 were statistically significant in univariate analysis...... discriminating between benign, borderline, and invasive tumors. Restricting the analysis of invasive tumors to early stage (I and II) showed similar results. A combination of CA125 and suPAR(I-III) + suPAR(II-III) discriminated between malignant (all stages) and benign tumors [AUC, 0.94; 95% confidence interval.......011) in multivariate analyses including age and CA125. CONCLUSIONS: High concentration of plasma uPAR(I) is an independent preoperative marker of poor prognosis in patients with ovarian cancer. The combination of plasma suPAR(I-III) + suPAR(II-III) and CA125 discriminates between malignant and benign tumors...

  1. Ovarian Tumor (OTU)-domain Containing Viral Proteases Evade Ubiquitin- and ISG15-dependent Innate Immune Responses

    Science.gov (United States)

    Frias-Staheli, Natalia; Giannakopoulos, Nadia V.; Kikkert, Marjolein; Taylor, Shannon L.; Bridgen, Anne; Paragas, Jason J.; Richt, Juergen A.; Rowland, Raymond R.; Schmaljohn, Connie S.; Lenschow, Deborah J.; Snijder, Eric J.; García-Sastre, Adolfo; Virgin, Herbert Whiting

    2007-01-01

    Summary Ubiquitin (Ub) and interferon stimulated gene product 15 (ISG15) reversibly conjugate to proteins via a conserved LRLRGG C-terminal motif, mediating important innate antiviral responses. The ovarian tumor (OTU) domain represents a superfamily of predicted proteases found in eukaryotic, bacterial and viral proteins, some of which have Ub-deconjugating activity. We show that the OTU domain-containing proteases of nairoviruses and arteriviruses hydrolyze Ub and ISG15 from cellular target proteins. This broad activity contrasts with the target specificity of known mammalian OTU domain-containing proteins. The biological significance of this activity of viral OTU domain-containing proteases was evidenced by their capacity to inhibit NF-κB dependent signaling and to antagonize the antiviral effects of ISG15 during Sindbis virus infection in vivo. The deconjugating activity of viral OTU proteases represents a novel viral immune evasion mechanism that inhibits Ub-and ISG15-dependent antiviral pathways. PMID:18078692

  2. Impact of lympho-vascular space invasion on tumor characteristics and survival outcome of women with low-grade serous ovarian carcinoma.

    Science.gov (United States)

    Matsuo, Koji; Wong, Kwong-Kwok; Fotopoulou, Christina; Blake, Erin A; Robertson, Sharon E; Pejovic, Tanja; Frimer, Marina; Pardeshi, Vishakha; Hu, Wei; Choi, Jong-Sun; Sun, Charlotte C; Richmond, Abby M; Marcus, Jenna Z; Hilliard, Maren A M; Mostofizadeh, Sayedamin; Mhawech-Fauceglia, Paulette; Abdulfatah, Eman; Post, Miriam D; Saglam, Ozlen; Shahzad, Mian M K; Karabakhtsian, Rouzan G; Ali-Fehmi, Rouba; Gabra, Hani; Roman, Lynda D; Sood, Anil K; Gershenson, David M

    2018-02-01

    To examine association of lympho-vascular space invasion (LVSI) with clinico-pathological factors and to evaluate survival of women with low-grade serous ovarian carcinoma containing areas of LVSI. This is a multicenter retrospective study examining consecutive cases of surgically treated stage I-IV low-grade serous ovarian carcinoma (n = 178). Archived histopathology slides for the ovarian tumors were reviewed, and LVSI was scored as present or absent. LVSI status was correlated to clinico-pathological findings and survival outcome. LVSI was seen in 79 cases (44.4%, 95% confidence interval [CI] 37.1-51.7). LVSI was associated with increased risk of omental metastasis (87.0% vs 64.9%, odds ratio [OR] 3.62, P = 0.001), high pelvic lymph node ratio (median 12.9% vs 0%, P = 0.012), and malignant ascites (49.3% vs 32.6%, OR 2.01, P = 0.035). On multivariable analysis, controlling for age, stage, and cytoreductive status, presence of LVSI in the ovarian tumor remained an independent predictor for decreased progression-free survival (5-year rates 21.0% vs 35.7%, adjusted-hazard ratio 1.57, 95%CI 1.06-2.34, P = 0.026). LVSI was significantly associated with increased risk of recurrence in lymph nodes (OR 2.62, 95%CI 1.08-6.35, P = 0.047). LVSI in the ovarian tumor is associated with adverse clinico-pathological characteristics and decreased progression-free survival in women with low-grade serous ovarian carcinoma. © 2017 Wiley Periodicals, Inc.

  3. Combined comparative genomic hybridization and transcriptomic analyses of ovarian granulosa cell tumors point to novel candidate driver genes.

    Science.gov (United States)

    Caburet, Sandrine; Anttonen, Mikko; Todeschini, Anne-Laure; Unkila-Kallio, Leila; Mestivier, Denis; Butzow, Ralf; Veitia, Reiner A

    2015-04-10

    Ovarian granulosa cell tumors (GCTs) are the most frequent sex cord-stromal tumors. Several studies have shown that a somatic mutation leading to a C134W substitution in the transcription factor FOXL2 appears in more than 95% of adult-type GCTs. Its pervasive presence suggests that FOXL2 is the main cancer driver gene. However, other mutations and genomic changes might also contribute to tumor formation and/or progression. We have performed a combined comparative genomic hybridization and transcriptomic analyses of 10 adult-type GCTs to obtain a picture of the genomic landscape of this cancer type and to identify new candidate co-driver genes. Our results, along with a review of previous molecular studies, show the existence of highly recurrent chromosomal imbalances (especially, trisomy 14 and monosomy 22) and preferential co-occurrences (i.e. trisomy 14/monosomy 22 and trisomy 7/monosomy 16q). In-depth analyses showed the presence of recurrently broken, amplified/duplicated or deleted genes. Many of these genes, such as AKT1, RUNX1 and LIMA1, are known to be involved in cancer and related processes. Further genomic explorations suggest that they are functionally related. Our combined analysis identifies potential candidate genes, whose alterations might contribute to adult-type GCT formation/progression together with the recurrent FOXL2 somatic mutation.

  4. Transplacental carcinogenicity of inorganic arsenic in the drinking water: induction of hepatic, ovarian, pulmonary, and adrenal tumors in mice

    International Nuclear Information System (INIS)

    Waalkes, Michael P.; Ward, Jerrold M.; Liu Jie; Diwan, Bhalchandra A.

    2003-01-01

    Arsenic is a known human carcinogen, but development of rodent models of inorganic arsenic carcinogenesis has been problematic. Since gestation is often a period of high sensitivity to chemical carcinogenesis, we performed a transplacental carcinogenicity study in mice using inorganic arsenic. Groups (n=10) of pregnant C3H mice were given drinking water containing sodium arsenite (NaAsO 2 ) at 0 (control), 42.5, and 85 ppm arsenite ad libitum from day 8 to 18 of gestation. These doses were well tolerated and body weights of the dams during gestation and of the offspring subsequent to birth were not reduced. Dams were allowed to give birth, and offspring were weaned at 4 weeks and then put into separate gender-based groups (n=25) according to maternal exposure level. The offspring received no additional arsenic treatment. The study lasted 74 weeks in males and 90 weeks in females. A complete necropsy was performed on all mice and tissues were examined by light microscopy in a blind fashion. In male offspring, there was a marked increase in hepatocellular carcinoma incidence in a dose- related fashion (control, 12%; 42.5 ppm, 38%; 85 ppm, 61%) and in liver tumor multiplicity (tumors per liver; 5.6-fold over control at 85 ppm). In males, there was also a dose-related increase in adrenal tumor incidence and multiplicity. In female offspring, dose-related increases occurred in ovarian tumor incidence (control, 8%; 42.5 ppm, 26%; 85 ppm, 38%) and lung carcinoma incidence (control, 0%; 42.5 ppm, 4%; 85 ppm, 21%). Arsenic exposure also increased the incidence of proliferative lesions of the uterus and oviduct. These results demonstrate that oral inorganic arsenic exposure, as a single agent, can induce tumor formation in rodents and establishes inorganic arsenic as a complete transplacental carcinogen in mice. The development of this rodent model of inorganic arsenic carcinogenesis has important implications in defining the mechanism of action for this common environmental

  5. Protein markers of cancer-associated fibroblasts and tumor-initiating cells reveal subpopulations in freshly isolated ovarian cancer ascites

    Directory of Open Access Journals (Sweden)

    Wintzell My

    2012-08-01

    Full Text Available Abstract Background In ovarian cancer, massive intraperitoneal dissemination is due to exfoliated tumor cells in ascites. Tumor-initiating cells (TICs or cancer stem cells and cells showing epithelial-mesenchymal-transition (EMT are particularly implicated. Spontaneous spherical cell aggregates are sometimes observed, but although similar to those formed by TICs in vitro, their significance is unclear. Methods Cells freshly isolated from malignant ascites were separated into sphere samples (S-type samples, n=9 and monolayer-forming single-cell suspensions (M-type, n=18. Using western blot, these were then compared for expression of protein markers of EMT, TIC, and of cancer-associated fibroblasts (CAFs. Results S-type cells differed significantly from M-type by expressing high levels of E-cadherin and no or little vimentin, integrin-β3 or stem cell transcription factor Oct-4A. By contrast, M-type samples were enriched for CD44, Oct-4A and for CAF markers. Independently of M- and S-type, there was a strong correlation between TIC markers Nanog and EpCAM. The CAF marker α-SMA correlated with clinical stage IV. This is the first report on CAF markers in malignant ascites and on SUMOylation of Oct-4A in ovarian cancer. Conclusions In addition to demonstrating potentially high levels of TICs in ascites, the results suggest that the S-type population is the less tumorigenic one. Nanoghigh/EpCAMhigh samples represent a TIC subset which may be either M- or S-type, and which is separate from the CD44high/Oct-4Ahigh subset observed only in M-type samples. This demonstrates a heterogeneity in TIC populations in vivo which has practical implications for TIC isolation based on cell sorting. The biological heterogeneity will need to be addressed in future therapeutical strategies.

  6. Protein markers of cancer-associated fibroblasts and tumor-initiating cells reveal subpopulations in freshly isolated ovarian cancer ascites

    International Nuclear Information System (INIS)

    Wintzell, My; Hjerpe, Elisabet; Åvall Lundqvist, Elisabeth; Shoshan, Maria

    2012-01-01

    In ovarian cancer, massive intraperitoneal dissemination is due to exfoliated tumor cells in ascites. Tumor-initiating cells (TICs or cancer stem cells) and cells showing epithelial-mesenchymal-transition (EMT) are particularly implicated. Spontaneous spherical cell aggregates are sometimes observed, but although similar to those formed by TICs in vitro, their significance is unclear. Cells freshly isolated from malignant ascites were separated into sphere samples (S-type samples, n=9) and monolayer-forming single-cell suspensions (M-type, n=18). Using western blot, these were then compared for expression of protein markers of EMT, TIC, and of cancer-associated fibroblasts (CAFs). S-type cells differed significantly from M-type by expressing high levels of E-cadherin and no or little vimentin, integrin-β3 or stem cell transcription factor Oct-4A. By contrast, M-type samples were enriched for CD44, Oct-4A and for CAF markers. Independently of M- and S-type, there was a strong correlation between TIC markers Nanog and EpCAM. The CAF marker α-SMA correlated with clinical stage IV. This is the first report on CAF markers in malignant ascites and on SUMOylation of Oct-4A in ovarian cancer. In addition to demonstrating potentially high levels of TICs in ascites, the results suggest that the S-type population is the less tumorigenic one. Nanog high /EpCAM high samples represent a TIC subset which may be either M- or S-type, and which is separate from the CD44 high /Oct-4A high subset observed only in M-type samples. This demonstrates a heterogeneity in TIC populations in vivo which has practical implications for TIC isolation based on cell sorting. The biological heterogeneity will need to be addressed in future therapeutical strategies

  7. Ovarian Brenner tumors and Walthard nests: a histologic and immunohistochemical study.

    Science.gov (United States)

    Roma, Andres A; Masand, Ramya P

    2014-12-01

    Brenner tumors are composed of urothelial/transitional-type epithelium and, hence, are morphologically similar to Walthard nests and tubal/mesothelial transitional metaplasia. In this study, we analyzed immunohistochemical markers on Brenner tumors to explore Müllerian as well as Wolffian and germ cell derivation. We also attempted to explore their possible association with tubal/paratubal Walthard nests/transitional metaplasia, using the same immunostains. Thirty-two consecutive cases of Brenner tumors were identified. Thirteen (43%) of the patients had Walthard nests in the tubal/periovarian soft tissue. All Brenner tumors were diffusely positive for GATA3 (strongly positive in 30/32 and weakly positive in the remaining 2) and negative for PAX8, PAX2, and SALL4. Similarly, all Walthard nests were positive for GATA3, whereas only 3 (23%) of 13 showed occasional PAX8 expression; all were negative for PAX2 and SALL4. In our study, more than 40% of Brenner tumors had associated Walthard nests. The similar morphology and immunoprofile of Brenner tumors and Walthard nests suggest a probable link between Brenner tumors and Walthard nests. Two additional cases presented highlight small transitional lesions involving the ovary: a possible precursor lesion or the initial steps of Brenner tumor formation. Brenner tumors and most Walthard nests lacked staining for Müllerian (PAX8 and PAX2) and germ cell tumor markers (SALL4). Copyright © 2014 Elsevier Inc. All rights reserved.

  8. [A Case with Metastatic Huge Ovarian Tumor from Transverse Colon Cancer, Who Underwent Systemic Chemotherapy after Bilateral Oophorectomy and Right Hemi Colectomy].

    Science.gov (United States)

    Miyanari, Shun; Nagasaki, Toshiya; Minami, Hironori; Fukuoka, Hironori; Murahashi, Satoshi; Suzuki, Shinsuke; Ushigome, Hajime; Akiyoshi, Takashi; Konishi, Tsuyoshi; Fujimoto, Yoshiya; Nagayama, Satoshi; Fukunaga, Yosuke; Ueno, Masashi

    2017-11-01

    Metastatic ovarian tumors from colon cancer would be resistant to chemotherapy, and compromising quality of life(QOL) of these patients was caused by acute enlargement of the tumors. A 37-year-old woman with abdominal distension was diagnosed with transverse colon cancer, bilateral ovarian metastases, liver metastases, and peritoneal dissemination at prior hospital. Two courses of chemotherapy(FOLFOX)were administered, but metastaticovarian tumors enlarged. Chemotherapy was discontinued and she was referred to our institution. To achieve symptom relief, improving QOL, and to resume chemotherapy, we planned bilateral oophorectomy and primary tumor resection if other stenotic lesion was not present. As a result, we safely performed open bilateral oophorectomy and right hemi colectomy, and the patient discharged on postoperative day 11 without complications. Chemotherapy was resumed and continued for 7 months up to this time. Even though, curative resection could not be achieved, oophorectomy should be performed in patients with enlarged metastatic ovarian tumor from colon cancer, in spite of administration of chemotherapy.

  9. Wilms tumor protein 1 (WT1)-- not only a diagnostic but also a prognostic marker in high-grade serous ovarian carcinoma.

    Science.gov (United States)

    Taube, Eliane Tabea; Denkert, Carsten; Sehouli, Jalid; Kunze, Catarina Alisa; Dietel, Manfred; Braicu, Ioana; Letsch, Anne; Darb-Esfahani, Silvia

    2016-03-01

    Wilms tumor protein 1 (WT1) expression is used in gynecological pathology as a diagnostic marker of serous differentiation, and is frequently co-expressed with ER-α. Early phase studies on WT1 vaccine in gynecological cancers are ongoing. In this study we aimed to determine the prognostic value of WT1 in high-grade serous ovarian carcinoma. WT1 protein expression was determined by immunohistochemistry in a cohort of 207 primary high-grade serous ovarian carcinomas. WT1 mRNA expression was evaluated in a cohort of 1137 ovarian carcinomas from publically available gene expression datasets. High WT1 expression was a significant positive prognostic factor in primary high-grade serous ovarian carcinoma regarding overall survival (OS, p=0.008) and progression free survival (PFS, p=0.015), which was independent of age, stage, and residual tumor (OS: p=0.024, PFS: p=0.047). The prognostic significance of immunohistochemical WT1 expression could be reproduced in an independent cohort of 72 patients. On the mRNA level the prognostic significance was validated in silico in publically available gene expression datasets including TCGA data (OS: p=0.002, PFS: p=0.011). WT1 expression was significantly linked to ER-α expression (p=0.001), and tumors that co-expressed both markers (WT1+/ER-α+) had a longer survival time than tumors of all other marker combinations (OS: p=0.002, PFS: p=0.013). We present WT1 as a robust prognostic marker in high-grade serous ovarian carcinoma, which adds prognostic information to ER-α. This should be kept in mind when WT1 is used as a biomarker in the context of WT1-targeting therapies. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. High efficacy of CpG-ODN, Cetuximab and Cisplatin combination for very advanced ovarian xenograft tumors

    Directory of Open Access Journals (Sweden)

    Sommariva Michele

    2013-01-01

    Full Text Available Abstract Background To mimic clinical treatment situations in advanced human ovarian disease, we tested the efficacy of CpG-oligodeoxynucleotides (CpG-ODN, synthetic DNA sequences recognized by Toll-like receptor 9 and able to induce innate/adaptive immune responses, in combination with other possible therapeutic reagents in ovarian carcinoma ascites-bearing athymic mice. Methods Mice injected i.p. with IGROV-1 ovarian cancer cells were treated at different stages of ascites progression for 4 weeks with CpG-ODN, alone or in combination with Bevacizumab, Polyinosinic:Polycytidylic acid (Poly(I:Poly(C, Gefitinib, Cetuximab and Cisplatin. Median survival time (MST was calculated for each group. IGROV-1 cells treated or not with Cetuximab were assayed for antibody-dependent cellular cytotoxicity by 51Cr-release assay, and for macrophage antibody-dependent cell-mediated phagocytosis by flow cytometry. Results In mice treated when ascitic fluid began to accumulate, CpG-ODN combined with Bevacizumab, Poly(I:Poly(C or Gefitinib did not significantly increase MST as compared with that using CpG-ODN alone, whereas MST in mice treated with CpG-ODN plus Cetuximab was significantly increased (>103 days for combination vs 62 days for CpG alone; P = 0.0008, with 4/8 mice alive at the end of the experiment. In experiments in mice showing increased abdominal volume and body weight (27.9 ± 0.8 g after vs 23 ± 1.1 g before tumor cell injection, treatment with Cisplatin in addition to CpG-ODN/Cetuximab led to significantly increased MST (105.5 days; P = 0.001, with all mice still alive at 85 days, over that using CpG-ODN/Cetuximab (66 days, Cetuximab/Cisplatin (18.5 days, Cisplatin (23 days or saline (16 days. At a very advanced stage of disease (body weight: 31.4 ± 0.9 g, when more than half of control mice had to be sacrificed 6 days after starting treatments, the triple-combination therapy still increased MST (45 days; P = 0.0089 vs

  11. Decreased expression of Beclin 1 correlates closely with Bcl-xL expression and poor prognosis of ovarian carcinoma.

    Directory of Open Access Journals (Sweden)

    Huan-Xin Lin

    Full Text Available It has been suggested that autophagy-related Beclin 1 plays a critical role in the regulation of tumor development and/or progression, but its prognostic significance and relationship with Bcl-xL expression in ovarian carcinoma are unclear.In the present study, the methods of Western blotting and immunohistochemistry (IHC were utilized to investigate the expression status of Beclin 1 and Bcl-xL in fresh ovarian tissues and paraffin-embedded epithelial ovarian tumor tissues. Decreased expression of Beclin 1 was examined by IHC in 8.3% of normal ovaries, in 15.4% of cystadenomas, in 20.0% of borderline tumors, and in 55.6% of ovarian carcinomas, respectively. In ovarian carcinomas, decreased expression of Beclin 1 was correlated closely with ascending histological grade, later pT/pN/pM status and/or advanced clinical stage (P<0.05. In univariate survival analysis, a highly significant association between low-expressed Beclin 1 and shortened patient survival was evaluated in ovarian carcinoma patients (P<0.01, and Beclin 1 expression was an independent prognostic factor as evidenced by multivariate analysis (P = 0.013. In addition, decreased expression of Beclin 1 was inversely correlated with altered expression of Bcl-xL in ovarian carcinoma cohort, and combined analysis further showed that the low Beclin 1/high Bcl-xL group had the lowest survival rate.Our findings suggest that Beclin 1 expression, as examined by IHC, could be served as an additional tool in identifying ovarian carcinoma patients at risk of tumor progression, and predicting patient survival in ovarian carcinomas with increased expression of Bcl-xL.

  12. Should CA-125 response criteria be preferred to response evaluation criteria in solid tumors (RECIST) for prognostication during second-line chemotherapy of ovarian carcinoma?

    DEFF Research Database (Denmark)

    Gronlund, Bo; Høgdall, Claus; Hilden, Jørgen

    2004-01-01

    PURPOSE: The aim of the study was to compare the prognostic value of a response by the Gynecologic Cancer Intergroup (GCIG) Cancer Antigen (CA) -125 response criteria and the Response Evaluation Criteria in Solid Tumors (RECIST) on survival in patients with ovarian carcinoma receiving second......-line chemotherapy. PATIENTS AND METHODS: From a single-institution registry of 527 consecutive patients with primary ovarian carcinoma, 131 records satisfied the inclusion criteria: ovarian carcinoma of International Federation of Gynecology and Obstetrics stage IC to IV, first-line chemotherapy with paclitaxel...... and a platinum compound, refractory or recurrent disease, and second-line chemotherapy consisting of topotecan or paclitaxel plus carboplatin. Univariate and multivariate analyses of survival were performed using the landmark method. RESULTS: In patients with measurable disease by RECIST and with assessable...

  13. Ovarian tumors among Nigerian females: A private practice experience in Benin-City, Nigeria

    Directory of Open Access Journals (Sweden)

    Gerald Dafe Forae

    2016-01-01

    Conclusion: Germ cell tumor was the most common with the majority occurring in reproductive age. Our finding is a reversal of what obtains in the western countries where surface epithelial tumor was the most common with the majority occurring in elderly females.

  14. Poly(adenosine diphosphate-ribose) polymerase expression in serous ovarian carcinoma: correlation with p53, MIB-1, and outcome.

    Science.gov (United States)

    Brustmann, Hermann

    2007-04-01

    This study investigated the expression of poly(adenosine diphosphate-ribose) polymerase (PARP) in a cohort of ovarian serous carcinomas by immunohistochemistry with regard to outcome, clinicopathologic parameters, proliferation as assessed by MIB-1 labeling indices (LIs), and p53 immunoexpression. Formalin-fixed, paraffin-embedded archival tissues of 50 ovarian serous carcinomas were immunostained with antibodies to PARP, MIB-1, and p53. In addition, 10 benign serous cystadenomas and 10 typical serous borderline ovarian tumors were included in the PARP immunostudy. Immunostaining for PARP was scored with regard to quantity and intensity of positively stained nuclei as negative, low, or strong. The MIB-1 LIs were quantitated as the percentage of positively stained nuclei in 1000 nuclei. For p53, at least 10% of tumor cells had to display nuclear staining. The expression of PARP was scored negative in all serous cystadenomas and low in serous borderline ovarian tumors. Strong PARP expression was determined in 38 cases (76%), and low expression in 12 cases (12%) of ovarian serous carcinomas; MIB-1 staining was noted in all cases (mean, 44.2; range, 10.8-66.5), positivity for p53 in 39 cases (78%). The PARP immunoreactivity increased with the International Federation of Gynecology and Obstetrics stage (P = 0.0075), as well as p53 positivity (P = 0.0141) and MIB-1 LIs (P = 0.0102), with grade determined after Malpica et al. (P = 0.0445) but not with grade assessed after Shimizu et al. (P = 0.1495). A trend for poor outcome was observed in patients whose tumors displayed high levels of PARP immunoexpression (P = 0.0196, log-rank test). This study indicates that PARP expression is frequently upregulated in ovarian serous carcinomas, related with MIB-1