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Sample records for cancer prognostic role

  1. Prognostic role of syncytin expression in breast cancer

    DEFF Research Database (Denmark)

    Larsson, Lars-Inge; Holck, Susanne; Christensen, Ib Jarle

    2007-01-01

    prognostic indicator for recurrence-free survival. In addition, we examined a second series of 54 consecutively operated breast cancer patients of all categories and the results supported the conclusions made from the first study. Thus, syncytin expression constitutes a positive prognostic factor in breast......Breast cancer cells were recently found to produce syncytin, an endogenous retroviral protein implicated in cell fusion, immune regulation, and nitric oxide synthase expression. To determine whether syncytin has a prognostic role in breast cancer, we investigated a series of 165 premenopausal lymph...... cancer - a phenomenon that may be related to the involvement of syncytin in mediating fusions between breast cancer cells and entodhelial cells....

  2. Prognostic Role of Common MicroRNA Polymorphisms in Cancers: Evidence from a Meta-Analysis

    OpenAIRE

    Xia, Lingzi; Ren, Yangwu; Fang, Xue; Yin, Zhihua; Li, Xuelian; Wu, Wei; Guan, Peng; Baosen ZHOU

    2014-01-01

    Background The morbidity and mortality of cancer increase remarkably every year. It's a heavy burden for family and society. The detection of prognostic biomarkers can help to improve the theraputic effect and prolong the lifetime of patients. microRNAs have an influential role in cancer prognosis. The results of articles discussing the relationship between microRNA polymorphisms and cancer prognosis are inconsistent. Methods We conduct a meta-analysis of 19 publications concerning the associ...

  3. Expression profile and prognostic role of sex hormone receptors in gastric cancer

    International Nuclear Information System (INIS)

    Increasing interest has been devoted to the expression and possible role of sex hormone receptors in gastric cancer, but most of these findings are controversial. In the present study, the expression profile of sex hormone receptors in gastric cancer and their clinicopathological and prognostic value were determined in a large Chinese cohort. The mRNA and protein expression of estrogen receptor alpha (ERα), estrogen receptor beta (ERβ), progesterone receptor (PR), and androgen receptor (AR) in primary gastric tumors and corresponding adjacent normal tissues from 60 and 866 Chinese gastric cancer patients was detected by real-time quantitative PCR and immunohistochemistry method, respectively. The expression profile of the four receptors was compared and their associations with clinicopathological characteristics were assessed by using Chi-square test. The prognostic value of the four receptors in gastric cancer was evaluated by using univariate and multivariate Cox regression analysis. The presence of ERα, ERβ, PR, and AR in both gastric tumors and normal tissues was confirmed but their expression levels were extremely low except for the predominance of ERβ. The four receptors were expressed independently and showed a decreased expression pattern in gastric tumors compared to adjacent normal tissues. The positive expression of the four receptors all correlated with high tumor grade and intestinal type, and ERα and AR were also associated with early TNM stage and thereby a favorable outcome. However, ERα and AR were not independent prognostic factors for gastric cancer when multivariate survival analysis was performed. Our findings indicate that the sex hormone receptors may be partly involved in gastric carcinogenesis but their clinicopathological and prognostic significance in gastric cancer appears to be limited

  4. The prognostic roles of ALDH1 isoenzymes in gastric cancer

    OpenAIRE

    Wang, Ziwei

    2016-01-01

    Kai Li,1,2 Xiaoguang Guo,3 Ziwei Wang,4 Xiaofeng Li,2 Youquan Bu,5 Xuefeng Bai,6 Liansheng Zheng,7 Ying Huang2 1Hepatobiliary Treatment Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 2Department of Medical Oncology, 3Surgical Department, Baotou Cancer Hospital, Baotou, Inner Mongolia, 4Department of Gastrointestinal Surgery, First Affiliated Hospital of Chongqing Medical University, Chongqing, 5Department of Biology, Chongqing Medical University, Chongqing,...

  5. The Prognostic and Clinicopathological Roles of Sirtuin-3 in Various Cancers.

    Science.gov (United States)

    Yu, Fei-Yuan; Xu, Qian; Wu, Dan-Dan; Lau, Andy T Y; Xu, Yan-Ming

    2016-01-01

    Sirtuin-3 (SIRT3) is a major mitochondrial NAD(+)-dependent deacetylase and plays a key role in the progression and development of human cancers. Although the prognostic and clinicopathological features of SIRT3 expression in various cancers have been investigated by different research groups, however, inconsistent and opposing results can be observed. In this study, we therefore performed a meta-analysis to evaluate the significance of SIRT3 expression in various cancers. Systematic literature searching was performed in PubMed, Embase, China National Knowledge Infrastructure, and Wanfang Data up to November 2015. Total effect analyses and subgroup analyses were performed to evaluate the relationship between SIRT3 expression and overall survival, cancer/non-cancer tissues, lymph node metastasis, pathological differentiation, tumor node metastasis (TNM) stage, tumor size, and gender, in various cancer patients. Hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to clarify the risk or hazard association. A total of 14 studies comprising 2165 cancer patients were included to assess the association between SIRT3 immunohistochemical expression and overall survival or clinicopathological characteristics. SIRT3 expression was significantly associated with overall survival in gastric cancer (HR = 0.62, 95% CI = 0.43-0.89, P = 0.009) and hepatocellular carcinoma patients (HR = 0.56, 95% CI = 0.42-0.74, Pcancer/non-cancer tissues in hepatocellular carcinoma patients (OR = 0.04, 95% CI = 0.01-0.16, Pcancer patients (OR = 2.20, 95% CI = 1.49-3.26, Pgastric cancer patients (OR = 0.33, 95% CI = 0.21-0.50, Plevel is associated with prognostic and clinical features in specific cancers. PMID:27483432

  6. Prognostic role of CD133 expression in colorectal cancer: a meta-analysis

    OpenAIRE

    Wang Ke; Xu Jianjun; Zhang Junshu; Huang Jian

    2012-01-01

    Abstract Background CD133 has been identified as a putative cancer stem cell marker in colorectal cancer (CRC). However, the clinical and prognostic significance of CD133 in CRC remains controversial. Methods Publications were identified which assessed the clinical or prognostic significance of CD133 in CRC up to October 2012. A meta-analysis was performed to clarify the association between CD133 expression and clinical outcomes. Results A total of 12 studies met the inclusion criteria, and c...

  7. Prognostic Significance and Functional Role of CEP57 in Prostate Cancer1

    Science.gov (United States)

    Mang, Josef; Korzeniewski, Nina; Dietrich, Dimo; Sailer, Verena; Tolstov, Yanis; Searcy, Sam; von Hardenberg, Jost; Perner, Sven; Kristiansen, Glen; Marx, Alexander; Roth, Wilfried; Herpel, Esther; Grüllich, Carsten; Popeneciu, Valentin; Pahernik, Sascha; Hadaschik, Boris; Hohenfellner, Markus; Duensing, Stefan

    2015-01-01

    We have recently shown that centrosomal protein 57 (CEP57) is overexpressed in a subset of human prostate cancers. CEP57 is involved in intracellular transport processes, and its overexpression causes mitotic defects as well as abnormal microtubule nucleation and bundling. In the present study, we further characterized the prognostic and functional role of CEP57 in prostate cancer. Unexpectedly, we found that high CEP57 expression is an independent prognostic factor for a more favorable biochemical recurrence-free survival in two large patient cohorts. To reconcile this finding with the ability of CEP57 to cause cell division errors and thus potentially promote malignant progression, we hypothesized that alterations of microtubule-associated transport processes, in particular nuclear translocation of the androgen receptor (AR), may play a role in our finding. However, CEP57 overexpression and microtubule bundling had, surprisingly, no effect on the nuclear translocation of the AR. Instead, we found a significant increase of cells with disarranged microtubules and a cellular morphology suggestive of a cytokinesis defect. Because mitotic dysfunction leads to a reduced daughter cell formation, it can explain the survival benefit of patients with increased CEP57 expression. In contrast, we show that a reduced expression of CEP57 is associated with malignant growth and metastasis. Taken together, our findings underscore that high CEP57 expression is associated with mitotic impairment and less aggressive tumor behavior. Because the CEP57-induced microtubule stabilization had no detectable effect on AR nuclear translocation, our results furthermore suggest that microtubule-targeting therapeutics used in advanced prostate cancer such as docetaxel may have modes of action that are at least in part independent of AR transport inhibition. PMID:26692530

  8. Prognostic role of tumor volume for radiotherapy outcome in patient with T2 laryngeal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Rutkowski, T.; Wygoda, A.; Skladowski, K.; Rutkowski, R.; Maciejewski, B. [Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Gliwice (Poland). Dept. of Radiation Oncology; Hejduk, B. [Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Gliwice (Poland). Dept. of Radiodiagnostic; Kolosza, Z. [Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Gliwice (Poland). Dept. of Epidemiology

    2013-10-15

    Background and purpose: Tumor volume (TV) is recognized as a prognostic factor of treatment outcome for head and neck tumors but is not routinely included in the treatment decision-making process. The purpose of the study was to define its prognostic role for patients with T2 laryngeal cancer. Material and methods: TV of 160 patients who underwent RT between 2002 and 2006 for T2 laryngeal squamous cell carcinoma were reviewed. The tumor was located in the glottis and epiglottis in 82 (51 %) and 78 (49 %) patients, respectively. TV was manually contoured on pretreatment, planning, contrast-enhanced CT scans and the volumetric measurement (cm{sup 3}) was calculated by the volume algorithm. Results: The median TV value was 2.01 cm{sup 3} (range 0.15-21.68 cm{sup 3}). The median TV was significantly lower in patients with glottic tumors (p < 0.0001), N0 (p < 0.001), or well histopatologically differentiated tumors (p = 0.01). A significant correlation between TV, hemoglobin concentration (p < 0.01), and total dose (TD; p < 0.001) was observed. On univariate analyses, TV influenced local control (LC; p = 0.02) and overall survival (OS, p < 0.001). On multivariate analysis, both age (HR 1.038, p = 0.03) and TV (HR = 1.075, p = 0.01) remained significantly related to LC and OS (age: HR 1.038, p = 0.005; TV: HR 1.097, p = 0.0001). Conclusion: Large TV worsen prognosis of patients with T2 laryngeal cancer. A large TV is more common for supraglottic, poorly differentiated tumors and may suggest higher risk of nodal spread. The routine estimation of TV prior to therapy may be essential in order to select the best treatment option for patients with T2 laryngeal cancer. (orig.)

  9. The Prognostic and Predictive Role of Epidermal Growth Factor Receptor in Surgical Resected Pancreatic Cancer.

    Science.gov (United States)

    Guo, Meng; Luo, Guopei; Liu, Chen; Cheng, He; Lu, Yu; Jin, Kaizhou; Liu, Zuqiang; Long, Jiang; Liu, Liang; Xu, Jin; Huang, Dan; Ni, Quanxing; Yu, Xianjun

    2016-01-01

    The data regarding the prognostic significance of EGFR (epidermal growth factor receptor) expression and adjuvant therapy in patients with resected pancreatic cancer are insufficient. We retrospectively investigated EGFR status in 357 resected PDAC (pancreatic duct adenocarcinoma) patients using tissue immunohistochemistry and validated the possible role of EGFR expression in predicting prognosis. The analysis was based on excluding the multiple confounding parameters. A negative association was found between overall EGFR status and postoperative survival (p = 0.986). Remarkably, adjuvant chemotherapy and radiotherapy were significantly associated with favorable postoperative survival, which prolonged median overall survival (OS) for 5.8 and 10.2 months (p = 0.009 and p = 0.006, respectively). Kaplan-Meier analysis showed that adjuvant chemotherapy correlated with an obvious survival benefit in the EGFR-positive subgroup rather than in the EGFR-negative subgroup. In the subgroup analyses, chemotherapy was highly associated with increased postoperative survival in the EGFR-negative subgroup (p = 0.002), and radiotherapy had a significant survival benefit in the EGFR-positive subgroup (p = 0.029). This study demonstrated that EGFR expression is not correlated with outcome in resected pancreatic cancer patients. Adjuvant chemotherapy and radiotherapy were significantly associated with improved survival in contrary EGFR expressing subgroup. Further studies of EGFR as a potential target for pancreatic cancer treatment are warranted. PMID:27399694

  10. Prognostic role of CD133 expression in colorectal cancer: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Wang Ke

    2012-12-01

    Full Text Available Abstract Background CD133 has been identified as a putative cancer stem cell marker in colorectal cancer (CRC. However, the clinical and prognostic significance of CD133 in CRC remains controversial. Methods Publications were identified which assessed the clinical or prognostic significance of CD133 in CRC up to October 2012. A meta-analysis was performed to clarify the association between CD133 expression and clinical outcomes. Results A total of 12 studies met the inclusion criteria, and comprised 3652 cases. Analysis of these data showed that CD133 was not significantly associated with the depth of CRC invasion (odds ratio [OR] = 1.44, 95% confidence interval [CI]: 0.77–2.68, Z = 1.15, P = 0.252 or tumor differentiation (OR = 0.63, 95% CI: 0.28–1.46, Z = −1.06, P = 0.286. Also, there was no statistically significant association of CD133 with lymph node metastasis (OR = 1.16, 95% CI: 0.87–1.54, Z = 1.05, P = 0.315 or lymphatic invasion (OR = 1.08, 95% CI: 0.81–1.43, Z = 0.53, P = 0.594. However, in identified studies, overexpression of CD133 was highly correlated with reduced overall survival (relative risk [RR] = 2.14, 95% CI: 1.45–3.17, Z = 3.81, P = 0.0001. Conclusions CD133 may play an important role in the progression of CRC, and overexpression of CD133 is closely related with poorer patient survival. If these findings are confirmed by well-designed prospective studies, CD133 may be a useful maker for clinical applications.

  11. The role of genetic breast cancer susceptibility variants as prognostic factors

    DEFF Research Database (Denmark)

    Fasching, Peter A; Pharoah, Paul D P; Cox, Angela;

    2012-01-01

    Recent genome-wide association studies identified 11 single nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk. We investigated these and 62 other SNPs for their prognostic relevance. Confirmed BC risk SNPs rs17468277 (CASP8), rs1982073 (TGFB1), rs2981582 (FGFR2), rs13281615 ...

  12. The prognostic role of classical and nonclassical MHC class I expression in endometrial cancer

    NARCIS (Netherlands)

    Bijen, C.B.; Bantema-Joppe, E.J.; de Jong, Renske; Leffers, N.; Mourits, M.J.; Eggink, Henk F.; van der Zee, A.G.; Hollema, H.; de Bock, G.H.; Nijman, H.W.

    2010-01-01

    The aim of this study was to investigate classical MHC class I and nonclassical MHC (human leukocyte antigen-G [HLA-GJ) expression in a large cohort of patients with endometrial cancer, to determine the prognostic value of these cell surface markers and their relation with clinicopathological variab

  13. A study of the prognostic role of serum fucose and fucosyl transferase in cancer of the uterine cervix.

    OpenAIRE

    Sen, Urmi; Guha,Subhas; Chowdhury, J Roy

    1985-01-01

    Serum fucose levels and fucosyl transferase activities have been designated as nonspecific markers of malignancy, and play an important role in the diagnosis of different types of malignancies. In the present study, attempts were made to determine the prognostic significance of these markers in patients with cancer of the uterine cervix after therapy. It was found that both serum fucose and fucosyl transferase, which were elevated in untreated patients declined significantly in patients respo...

  14. Genome-wide profiling of transfer RNAs and their role as novel prognostic markers for breast cancer

    Science.gov (United States)

    Krishnan, Preethi; Ghosh, Sunita; Wang, Bo; Heyns, Mieke; Li, Dongping; Mackey, John R.; Kovalchuk, Olga; Damaraju, Sambasivarao

    2016-01-01

    Transfer RNAs (tRNAs, key molecules in protein synthesis) have not been investigated as potential prognostic markers in breast cancer (BC), despite early findings of their dysregulation and diagnostic potential. We aim to comprehensively profile tRNAs from breast tissues and to evaluate their role as prognostic markers (Overall Survival, OS and Recurrence Free Survival, RFS). tRNAs were profiled from 11 normal breast and 104 breast tumor tissues using next generation sequencing. We adopted a Case-control (CC) and Case-Only (CO) association study designs. Risk scores constructed from tRNAs were subjected to univariate and multivariate Cox-proportional hazards regression to investigate their prognostic value. Of the 571 tRNAs profiled, 76 were differentially expressed (DE) and three were significant for OS in the CC approach. We identified an additional 11 tRNAs associated with OS and 14 tRNAs as significant for RFS in the CO approach, indicating that CC alone may not capture all discriminatory tRNAs in prognoses. In both the approaches, the risk scores were significant in the multivariate analysis as independent prognostic factors, and patients belonging to high-risk group were associated with poor prognosis. Our results confirmed global up-regulation of tRNAs in BC and identified tRNAs as potential novel prognostic markers for BC. PMID:27604545

  15. Genome-wide profiling of transfer RNAs and their role as novel prognostic markers for breast cancer.

    Science.gov (United States)

    Krishnan, Preethi; Ghosh, Sunita; Wang, Bo; Heyns, Mieke; Li, Dongping; Mackey, John R; Kovalchuk, Olga; Damaraju, Sambasivarao

    2016-01-01

    Transfer RNAs (tRNAs, key molecules in protein synthesis) have not been investigated as potential prognostic markers in breast cancer (BC), despite early findings of their dysregulation and diagnostic potential. We aim to comprehensively profile tRNAs from breast tissues and to evaluate their role as prognostic markers (Overall Survival, OS and Recurrence Free Survival, RFS). tRNAs were profiled from 11 normal breast and 104 breast tumor tissues using next generation sequencing. We adopted a Case-control (CC) and Case-Only (CO) association study designs. Risk scores constructed from tRNAs were subjected to univariate and multivariate Cox-proportional hazards regression to investigate their prognostic value. Of the 571 tRNAs profiled, 76 were differentially expressed (DE) and three were significant for OS in the CC approach. We identified an additional 11 tRNAs associated with OS and 14 tRNAs as significant for RFS in the CO approach, indicating that CC alone may not capture all discriminatory tRNAs in prognoses. In both the approaches, the risk scores were significant in the multivariate analysis as independent prognostic factors, and patients belonging to high-risk group were associated with poor prognosis. Our results confirmed global up-regulation of tRNAs in BC and identified tRNAs as potential novel prognostic markers for BC. PMID:27604545

  16. Prognostic Factors in Pancreatic Cancer

    OpenAIRE

    Åke Andrén-Sandberg

    2012-01-01

    Prognostic factors in pancreatic cancer have been a hot topic for the clinical pancreatology, and many studies have been involved in the field. The author reviewed the pancreatic abstracts of American Pancreas Club 2011, and sumarized "highlight" of all the abstracts in prognostic factors in pancreatic cancer.

  17. Evaluation of prognostic and predictive factors in breast cancer in Cuba. Its role in personalized therapy

    International Nuclear Information System (INIS)

    The identification of prognostic and predictive factors in breast cancer has allowed applying personalized therapeutic programs without achieving, still, the individualization for all patients. The objective of the present study was to evaluate the frequency of estrogen receptors, progesterone and HER2 along with the expression of the EGFR1 and ganglioside NglicolilGM3. 1509 patients found the frequency of expression of the aforementioned receivers, which were correlated with the morphological and General variables. It was compared the AcM recognition ior egf/r3 with a game of diagnosis - shopping, and the AcM 14F7 vitro tissue fresh and included in paraffin and in vivo labelled with 99mTc. It was obtained the frequency in Cuba of these prognostic and prediction markers of response, noting her hormone dependence of tumor associated with less aggressive features. The AcM 14F7 showed a broad recognition that was not correlated with prognostic factors, but was able to detect live in primary breast tumors. The ior egf/r3 exhibited 100% specificity and positive predictive value, as well as a sensitivity and negative predictive value of 68 and 73% respectively. The recognition of the AcM 14F7 and ior egf/r3 opens a new possibility of therapeutic directed against these targets for breast cancer (author)

  18. The role of PET/CT as a prognosticator and outcome predictor in lung cancer.

    Science.gov (United States)

    Khiewvan, Benjapa; Ziai, Pouya; Houshmand, Sina; Salavati, Ali; Ziai, Peyman; Alavi, Abass

    2016-03-01

    Positron emission tomography/computed tomography (PET/CT) is an important imaging tool for management of lung cancer and can be utilized in diagnosis, staging, restaging, treatment planning and evaluating treatment response. In the past decade PET/CT has proven to be beneficial for the prediction of prognosis and outcome. PET findings before and after treatment, the quantitative PET parameters such as standardized uptake value (SUV), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) as well as delayed PET/CT imaging can be used to determine patient prognosis and outcome. Other tracers such as hypoxia and proliferation marker tracers may be used for prognostication. The prognostic factors derived from PET/CT imaging help early development of risk-adapted treatment strategies, which provides cost-effective treatment and leads to improved patient management. Here, we discuss findings of studies related to application of PET/CT in lung cancer as well as some technical updates on quantitative PET/CT in lung cancer. PMID:26822467

  19. Prognostic factors of breast cancer

    International Nuclear Information System (INIS)

    The prognostic factors must to be differentiated of the predictive ones. A prognostic factor is any measurement used at moment of the surgery correlated with the free interval of disease or global survival in the absence of the systemic adjuvant treatment and as result is able to correlate with the natural history of the disease. In contrast, a predictive factor is any measurement associated with the response to a given treatment. Among the prognostic factors of the breast cancer are included the clinical, histological, biological, genetic and psychosocial factors. In present review of psychosocial prognostic factors has been demonstrated that the stress and the depression are negative prognostic factors in patients presenting with breast cancer. It is essential to remember that the assessment of just one prognostic parameter is a help but it is not useful to clinical and therapeutic management of the patient.(author)

  20. Age determines the prognostic role of the cancer stem cell marker aldehyde dehydrogenase-1 in breast cancer

    Directory of Open Access Journals (Sweden)

    Mieog J Sven D

    2012-01-01

    Full Text Available Abstract Background The purpose of this study was to compare the expression and the prognostic effect of the breast cancer stem cell marker aldehyde dehydrogenase-1 (ALDH1 in young and elderly breast cancer patients. Methods The study population (N = 574 consisted of all early breast cancer patients primarily treated with surgery in our center between 1985 and 1994. Median follow-up was 17.9 years (range: 0.1 to 23.5. Tissue microarray slides were immunohistochemically stained for ALDH1 expression and quantified by two independent observers who were blinded to clinical outcome. Assessment of the prognostic effect of ALDH1 expression was stratified according to age and systemic treatment. Results Complete lack of expression of ALDH1 was found in 40% of tumors. With increasing age more tumors showed complete absence of ALDH1 expression (P 65 years, ALDH1 status was not associated with any clinical outcome. Conversely, in patients aged P = .021 and relative survival (relative excess risks of death = 2.36 (95% CI, 1.22 to 3.68; P = .016. Ten-year relative survival risk was 57% in ALDH1-positive patients compared to 83% in ALDH1-negative patients. Conclusion ALDH1 expression and its prognostic effect are age-dependent. Our results support the hypothesis that breast cancer biology is different in elderly patients compared to their younger counterparts and emphasizes the importance of taking into consideration age-specific interactions in breast cancer research.

  1. Prognostic role of LSD1 in various cancers: evidence from a meta-analysis

    Directory of Open Access Journals (Sweden)

    Wu J

    2015-09-01

    Full Text Available Jin Wu,1,* Lixia Hu,2,* Yingying Du,3 Fanliang Kong,2 Yueyin Pan31The Central Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Department of Oncology, The Second People’s Hospital of Hefei, Hefei, Anhui, People’s Republic of China; 3Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China *These authors contributed equally to this work and should be considered as co-first authors Abstract: The prognostic value of lysine-specific demethylase 1 (LSD1 overexpression in various cancers has been investigated by many studies with inconsistent results. A meta-analysis was performed to assess the association between LSD1 and overall survival (OS in cancer patients. Eligible studies were identified by searching the online databases PubMed and China National Knowledge Infrastructure up to February 2015. Hazard ratios (HRs with 95% confidence intervals (CIs were calculated to clarify the correlation between LSD1 expression and prognosis of different cancers. In total, nine studies with 1,149 cancer patients were included for final analysis. The meta-analysis suggested that LSD1 overexpression was associated with poor OS in cancer patients (HR =1.80, 95% CI: 1.39–2.34, P=0.000. Subgroup analysis by ethnicity, cancer type and HR estimate also showed that high levels of LSD1 were significantly correlated with OS. The meta-analysis showed that LSD1 overexpression may be associated with a worse prognosis in cancer patients.Keywords: LSD1, cancer, prognosis, meta-analysis, overall survival

  2. A study of the prognostic role of serum fucose and fucosyl transferase in cancer of the uterine cervix.

    Directory of Open Access Journals (Sweden)

    Sen,Urmi

    1985-04-01

    Full Text Available Serum fucose levels and fucosyl transferase activities have been designated as nonspecific markers of malignancy, and play an important role in the diagnosis of different types of malignancies. In the present study, attempts were made to determine the prognostic significance of these markers in patients with cancer of the uterine cervix after therapy. It was found that both serum fucose and fucosyl transferase, which were elevated in untreated patients declined significantly in patients responsive to therapy at different follow-up intervals, but not in patients unresponsive to therapy.

  3. Different prognostic roles of tumor suppressor gene BAP1 in cancer: A systematic review with meta-analysis.

    Science.gov (United States)

    Luchini, Claudio; Veronese, Nicola; Yachida, Shinichi; Cheng, Liang; Nottegar, Alessia; Stubbs, Brendon; Solmi, Marco; Capelli, Paola; Pea, Antonio; Barbareschi, Mattia; Fassan, Matteo; Wood, Laura D; Scarpa, Aldo

    2016-10-01

    Biallelic inactivation of the tumor suppressor gene BRCA1-associated protein 1 (BAP1) has been demonstrated in several cancers, but its prognostic role has not been completely explained. We aimed to investigate the risk associated with loss of BAP1 (BAP1-) for all-cause mortality, cancer-specific mortality and recurrence of disease in subjects with cancer. PubMed and SCOPUS were searched from database inception until 09/15/2015 without language restrictions. Prospective studies reporting data on prognostic parameters in subjects with cancer, comparing participants with presence of BAP1 (BAP1+) vs. BAP1- were included. Data were summarized using risk ratios (RR) for number of deaths/recurrences and hazard ratios (HR) for time-dependent risk related to BAP1- adjusted for potential confounders. From 261 hits, 12 studies (including 13 cohorts) with 3,447 participants (BAP1-: n = 697; BAP1+: n = 2,750), with a median follow-up over 60 months, were meta-analyzed. Compared to BAP1+, BAP1- significantly increased all-cause mortality, cancer-specific mortality and risk of recurrence in all the tumor types analyzed, except for mesothelioma, in which the presence of BAP1 mutations correlates with a better prognosis. Furthermore, we demonstrated that BAP1 mutated colorectal and renal carcinomas are associated with high-tumor grading (P < 0.0001), and that BAP1 mutated is more common in women than in men (P < 0.0001). In conclusion, on the basis of our meta-analysis, we have demonstrated a peculiar role of BAP1 in influencing the prognosis in cancer. Thus, BAP1 could be considered as an important potential target for personalized medicine. © 2016 Wiley Periodicals, Inc. PMID:27223342

  4. Prognostic Role of Phospho-STAT3 in Patients with Cancers of the Digestive System: A Systematic Review and Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Mu-xing Li

    Full Text Available The definite prognostic role of p-STAT3 has not been well defined. We performed a meta-analysis evaluating the prognostic role of p-STAT3 expression in patients with digestive system cancers.We searched the available articles reporting the prognostic value of p-STAT3 in patients with cancers of the digestive system, mainly including colorectal cancer, gastric cancer, hepatocellular carcinoma, esophagus cancer and pancreatic cancer. The pooled hazard ratios (HRs with 95 % confidence intervals (95 % CIs of overall survival (OS and disease-free survival (DFS were used to assess the prognostic role of p-STAT3 expression level in cancer tissues. And the association between p-STAT3 expression and clinicopathological characteristics was evaluated.A total of 22 studies with 3585 patients were finally enrolled in the meta-analysis. The results showed that elevated p-STAT3 expression level predicted inferior OS (HR = 1.809, 95% CI: 1.442-2.270, P < 0.001 and DFS (HR = 1.481, 95% CI: 1.028-2.133, P = 0.035 in patients with malignant cancers of the digestive system. Increased expression of p-STAT3 is significantly related with tumor cell differentiation (Odds ratio (OR = 1.895, 95% CI: 1.364-2.632, P < 0.001 and lymph node metastases (OR = 2.108, 95% CI: 1.104-4.024, P = 0.024. Sensitivity analysis suggested that the pooled HR was stable and omitting a single study did not change the significance of the pooled HR. Funnel plots and Egger's tests revealed there was no significant publication bias in the meta-analysis.Phospho-STAT3 might be a prognostic factor of patients with digestive system cancers. More well designed studies with adequate follow-up are needed to gain a thorough understanding of the prognostic role of p-STAT3.

  5. Immune Cells in Colorectal Cancer: Prognostic Relevance and Role of MSI

    OpenAIRE

    Deschoolmeester, Vanessa; Baay, Marc; Lardon, Filip; Pauwels, Patrick; Peeters, Marc

    2011-01-01

    There is growing evidence that both local and systemic inflammatory responses play an important role in the progression of a variety of solid tumors. Colorectal cancer (CRC) results from the cumulative effect of sequential genetic alterations, leading to the expression of tumor-associated antigens possibly inducing a cellular anti-tumor immune response. It is well recognized that cytotoxic lymphocytes (CTLs) constitute one of the most important effector mechanisms of anti-tumor-immunity. Howe...

  6. The role of genetic breast cancer susceptibility variants as prognostic factors.

    Science.gov (United States)

    Fasching, Peter A; Pharoah, Paul D P; Cox, Angela; Nevanlinna, Heli; Bojesen, Stig E; Karn, Thomas; Broeks, Annegien; van Leeuwen, Flora E; van't Veer, Laura J; Udo, Renate; Dunning, Alison M; Greco, Dario; Aittomäki, Kristiina; Blomqvist, Carl; Shah, Mitul; Nordestgaard, Børge G; Flyger, Henrik; Hopper, John L; Southey, Melissa C; Apicella, Carmel; Garcia-Closas, Montserrat; Sherman, Mark; Lissowska, Jolanta; Seynaeve, Caroline; Huijts, Petra E A; Tollenaar, Rob A E M; Ziogas, Argyrios; Ekici, Arif B; Rauh, Claudia; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Andrulis, Irene L; Ozcelik, Hilmi; Mulligan, Anna-Marie; Glendon, Gord; Hall, Per; Czene, Kamila; Liu, Jianjun; Chang-Claude, Jenny; Wang-Gohrke, Shan; Eilber, Ursula; Nickels, Stefan; Dörk, Thilo; Schiekel, Maria; Bremer, Michael; Park-Simon, Tjoung-Won; Giles, Graham G; Severi, Gianluca; Baglietto, Laura; Hooning, Maartje J; Martens, John W M; Jager, Agnes; Kriege, Mieke; Lindblom, Annika; Margolin, Sara; Couch, Fergus J; Stevens, Kristen N; Olson, Janet E; Kosel, Matthew; Cross, Simon S; Balasubramanian, Sabapathy P; Reed, Malcolm W R; Miron, Alexander; John, Esther M; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; Burwinkel, Barbara; Marme, Frederik; Schneeweiss, Andreas; Sohn, Christof; Chenevix-Trench, Georgia; Lambrechts, Diether; Dieudonne, Anne-Sophie; Hatse, Sigrid; van Limbergen, Erik; Benitez, Javier; Milne, Roger L; Zamora, M Pilar; Pérez, José Ignacio Arias; Bonanni, Bernardo; Peissel, Bernard; Loris, Bernard; Peterlongo, Paolo; Rajaraman, Preetha; Schonfeld, Sara J; Anton-Culver, Hoda; Devilee, Peter; Beckmann, Matthias W; Slamon, Dennis J; Phillips, Kelly-Anne; Figueroa, Jonine D; Humphreys, Manjeet K; Easton, Douglas F; Schmidt, Marjanka K

    2012-09-01

    Recent genome-wide association studies identified 11 single nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk. We investigated these and 62 other SNPs for their prognostic relevance. Confirmed BC risk SNPs rs17468277 (CASP8), rs1982073 (TGFB1), rs2981582 (FGFR2), rs13281615 (8q24), rs3817198 (LSP1), rs889312 (MAP3K1), rs3803662 (TOX3), rs13387042 (2q35), rs4973768 (SLC4A7), rs6504950 (COX11) and rs10941679 (5p12) were genotyped for 25 853 BC patients with the available follow-up; 62 other SNPs, which have been suggested as BC risk SNPs by a GWAS or as candidate SNPs from individual studies, were genotyped for replication purposes in subsets of these patients. Cox proportional hazard models were used to test the association of these SNPs with overall survival (OS) and BC-specific survival (BCS). For the confirmed loci, we performed an accessory analysis of publicly available gene expression data and the prognosis in a different patient group. One of the 11 SNPs, rs3803662 (TOX3) and none of the 62 candidate/GWAS SNPs were associated with OS and/or BCS at PBreast tumor expression of these genes was not associated with prognosis. With the exception of rs3803662 (TOX3), there was no evidence that any of the SNPs associated with BC susceptibility were associated with the BC survival. Survival may be influenced by a distinct set of germline variants from those influencing susceptibility. PMID:22532573

  7. Potential role of nuclear PD-L1 expression in cell-surface vimentin positive circulating tumor cells as a prognostic marker in cancer patients.

    Science.gov (United States)

    Satelli, Arun; Batth, Izhar Singh; Brownlee, Zachary; Rojas, Christina; Meng, Qing H; Kopetz, Scott; Li, Shulin

    2016-01-01

    Although circulating tumor cells (CTCs) have potential as diagnostic biomarkers for cancer, determining their prognostic role in cancer patients undergoing treatment is a challenge. We evaluated the prognostic value of programmed death-ligand 1 (PD-L1) expression in CTCs in colorectal and prostate cancer patients undergoing treatment. Peripheral blood samples were collected from 62 metastatic colorectal cancer patients and 30 metastatic prostate cancer patients. CTCs were isolated from the samples using magnetic separation with the cell-surface vimentin(CSV)-specific 84-1 monoclonal antibody that detects epithelial-mesenchymal transitioned (EMT) CTCs. CTCs were enumerated and analyzed for PD-L1 expression using confocal microscopy. PD-L1 expression was detectable in CTCs and was localized in the membrane and/or cytoplasm and nucleus. CTC detection alone was not associated with poor progression-free or overall survival in colorectal cancer or prostate cancer patients, but nuclear PD-L1 (nPD-L1) expression in these patients was significantly associated with short survival durations. These results demonstrated that nPD-L1 has potential as a clinically relevant prognostic biomarker for colorectal and prostate cancer. Our data thus suggested that use of CTC-based models of cancer for risk assessment can improve the standard cancer staging criteria and supported the incorporation of nPD-L1 expression detection in CTCs detection in such models. PMID:27363678

  8. Potential role of nuclear PD-L1 expression in cell-surface vimentin positive circulating tumor cells as a prognostic marker in cancer patients

    Science.gov (United States)

    Satelli, Arun; Batth, Izhar Singh; Brownlee, Zachary; Rojas, Christina; Meng, Qing H.; Kopetz, Scott; Li, Shulin

    2016-01-01

    Although circulating tumor cells (CTCs) have potential as diagnostic biomarkers for cancer, determining their prognostic role in cancer patients undergoing treatment is a challenge. We evaluated the prognostic value of programmed death-ligand 1 (PD-L1) expression in CTCs in colorectal and prostate cancer patients undergoing treatment. Peripheral blood samples were collected from 62 metastatic colorectal cancer patients and 30 metastatic prostate cancer patients. CTCs were isolated from the samples using magnetic separation with the cell-surface vimentin(CSV)-specific 84-1 monoclonal antibody that detects epithelial-mesenchymal transitioned (EMT) CTCs. CTCs were enumerated and analyzed for PD-L1 expression using confocal microscopy. PD-L1 expression was detectable in CTCs and was localized in the membrane and/or cytoplasm and nucleus. CTC detection alone was not associated with poor progression-free or overall survival in colorectal cancer or prostate cancer patients, but nuclear PD-L1 (nPD-L1) expression in these patients was significantly associated with short survival durations. These results demonstrated that nPD-L1 has potential as a clinically relevant prognostic biomarker for colorectal and prostate cancer. Our data thus suggested that use of CTC-based models of cancer for risk assessment can improve the standard cancer staging criteria and supported the incorporation of nPD-L1 expression detection in CTCs detection in such models. PMID:27363678

  9. Prevalence and Prognostic Role of BRCA1/2 Variants in Unselected Chinese Breast Cancer Patients

    Science.gov (United States)

    Li, Jiayuan; Peng, Zuxiang; Deng, Ling; Zhu, Xuehua; Sun, Yun; Lu, Xuesong; Shen, Fuxiao; Su, Xinying; Zhang, Liying; Gu, Yi; Zheng, Hong

    2016-01-01

    Background The prevalence of BRCA1/2 variants in Chinese breast cancer patients varies among studies. Germline or somatic BRCA1/2 mutations are associated with sensitivity to poly(ADP-ribose) polymerase-1 inhibitors and DNA-damaging agents. We aimed to investigate the distribution of both somatic and germline BRCA1/2 variants in unselected Chinese breast cancer patients, and explore their roles in tumor phenotype and disease prognosis. Methods 507 breast cancer patients, unselected for family history of breast cancer or age at diagnosis, were prospectively enrolled from West China Hospital between Feb. 2008 and Feb. 2014. BRCA1/2 variants in the exons/flanking regions were detected in fresh-frozen tumors using next-generation sequencing and confirmed by independent methods. Germline/somatic status was validated by Sanger sequencing in paired blood/normal tissue. Results BRCA1/2 pathogenic or likely pathogenic (P/LP) variants were detected in 50 patients (9.9%), including 40 germline carriers (18 in BRCA1, 22 in BRCA2), 9 patients with somatic variants (3 in BRCA1, 6 in BRCA2), and 1 patient with concurrent germline/somatic variants in BRCA2. The triple-negative (21.4%) and Luminal B (9.7%) subtypes had higher rates of BRCA1/2 variants. In patients with disease stage 0~II, presence of a germline or somatic BRCA1 P/LP variant increased the risk of relapse as compared to non-carriers [univariate hazard ratio (HR): 3.70, P = 0.04]. Germline BRCA1 P/LP variants, which were associated with aggressive tumor phenotypes, predicted worse disease-free survival in the subgroup of stage 0~II (HR: 4.52, P = 0.02) and N0 (HR: 5.4, P = 0.04) compared to non-carriers. Conclusion A high frequency of germline and somatic BRCA1/2 P/LP variants was detected in unselected Chinese breast cancer patients. Luminal B subtype should be considered as a high-risk population of BRCA1/2 mutation, in addition to triple-negative breast cancer. BRCA1 status was associated with aggressive tumor

  10. Prognostic factors in prostate cancer.

    Science.gov (United States)

    Braeckman, Johan; Michielsen, Dirk

    2007-01-01

    In the nineteenth century the main goal of medicine was predictive: diagnose the disease and achieve a satisfying prognosis of the patient's chances. Today the effort has shifted to cure the disease. Since the twentieth century, the word prognosis has also been used in nonmedical contexts, for example in corporate finance or elections. The most accurate form of prognosis is achieved statistically. Based on different prognostic factors it should be possible to tell patients how they are expected to do after prostate cancer has been diagnosed and how different treatments may change this outcome. A prognosis is a prediction. The word prognosis comes from the Greek word (see text) and means foreknowing. In the nineteenth century this was the main goal of medicine: diagnose the disease and achieve a satisfying prognosis of the patient's chances. Today the effort has shifted towards seeking a cure. Prognostic factors in (prostate) cancer are defined as "variables that can account for some of the heterogeneity associated with the expected course and outcome of a disease". Bailey defined prognosis as "a reasoned forecast concerning the course, pattern, progression, duration, and end of the disease. Prognostic factors are not only essential to understand the natural history and the course of the disease, but also to predict possible different outcomes of different treatments or perhaps no treatment at all. This is extremely important in a disease like prostate cancer where there is clear evidence that a substantial number of cases discovered by prostate-specific antigen (PSA) testing are unlikely ever to become clinically significant, not to mention mortal. Furthermore, prognostic factors are of paramount importance for correct interpretation of clinical trials and for the construction of future trials. Finally, according to WHO national screening committee criteria for implementing a national screening programme, widely accepted prognostic factors must be defined before

  11. Prognostic role of PIK3CA mutations of cell‐free DNA in early‐stage triple negative breast cancer

    OpenAIRE

    Takeshita, Takashi; Yamamoto, Yutaka; Yamamoto‐Ibusuki, Mutsuko; Inao, Toko; Sueta, Aiko; Fujiwara, Saori; Omoto, Yoko; Iwase, Hirotaka

    2015-01-01

    PIK3CA is an oncogene that encodes the p110α component of phosphatidylinositol 3‐kinase (PI3K); it is the second most frequently mutated gene following the TP53 gene. In the clinical setting, PIK3CA mutations may have favorable prognostic value for hormone receptor‐positive breast cancer patients and, during the past few years, PIK3CA mutations of cell‐free DNA (cfDNA) have attracted attention as a potential noninvasive biomarker of cancer. However, there are few reports on the clinical impli...

  12. Prognostic Role of a Soluble Fas in Patients with a Mammary Gland Cancer

    OpenAIRE

    Ozhereliev A.S.; Komov D.V.; Abbasova S.G.; Orinovsky M.B.; Kolyadina I.V.; Ovtchinnickova L.K.; Tuleuova A.A.; Grishkevich M.V.; Mamedov U.R.; Karabeckova Z.K.; Vorotnickov I.K.

    2010-01-01

    The results of a comparative study of the soluble Fas (sFas) levels in a blood serum of the healthy females (n=55) and patients with a mammary gland cancer (MGC) in a stage of T1N0M0 (n=76) and T2N0M0 (n=172), the connections of sFas with the basic clinicomorphologic factors and a disease prognosis are presented. The sFas is revealed with a similar rate in a blood serum and patients with a mammary gland cancer both in a stage of T1N0M0 (53.9%) and in a stage of T2N0M0 (59.3%), and in healthy ...

  13. Prognostic Role of BRAF Mutation in Stage II/III Colorectal Cancer Receiving Curative Resection and Adjuvant Chemotherapy: A Meta-Analysis Based on Randomized Clinical Trials

    Science.gov (United States)

    Cao, Ying; Fang, Xuefeng; Zhong, Chenhan; Li, Dan; Yuan, Ying

    2016-01-01

    Background and Objective Studies examining the prognostic value of the BRAF mutation on relapse-free survival (RFS), disease-free survival (DFS) and overall survival (OS) in stage II/III colorectal cancer (CRC) patients receiving curative resection and adjuvant chemotherapy so far showed discrepant results. Therefore, a meta-analysis of relevant studies was performed for clarification. Methods Randomized trials of stage II/III colorectal cancer treated with curative resection followed by adjuvant chemotherapy were selected to conduct a meta-analysis. The necessary descriptive and statistical information such as hazard ratios (HRs) and 95% confidence intervals (CIs) were derived from published survival data. Results Seven phase III randomized clinical trials (RCTs) including 1,035 BRAF mutation stage II/III CRC patients receiving curative resection and adjuvant chemotherapy were analyzed. Overall, BRAF mutation resulted in poorer OS (HR = 1.42, 95% CI: 1.25–1.60; P < 0.00001), and poorer DFS (HR = 1.26, 95% CI: 1.07–1.48, P = 0.006) compared with BRAF wild-type CRC. The prognostic role on RFS could not be elucidated in the meta-analysis because of limited data. Conclusions BRAF mutation was significantly related with shorter DFS and OS among stage II/III CRC patients receiving adjuvant chemotherapy after curative resection. Its prognostic role for RFS needs to be further analyzed when more data is available. PMID:27138801

  14. Role of radiotherapy and prognostic factors in breast cancer patients at high-risk of recurrence treated with modified radical mastectomy and chemotherapy

    International Nuclear Information System (INIS)

    Objective: To analyze the outcome and prognostic factors in breast cancer at high-risk of recurrence and evaluate the role of radiotherapy. Methods: 381 breast cancer patients treated with mastectomy and axillary dissection were retrospectively analyzed. The including criterias were pathologic diagnosis of invasive breast cancer, T3-T4 and/or four or more positive axillary nodes. The survival rates was calculated by Kaplan-Meier method, and compared by Logrank test. Cox regression model was used to select potential prognostic variables. Results: The median follow up was 48 months. The 5-year overall survival (OS) and locoregional recurrence-free survival (LRFS) rates were 76.8% and 89.7%, respectively. Radiotherapy significantly improved the OS (80.9% vs. 62.3%, χ2=15.47, P=0.001) and LRFS (93.4% vs. 77.1%, χ2=19.95, P=0.000). The use of ipsilateral chest wall and supraclavicular nodal radiation was associated with increased 5-year chest wall recurrence free survival (96.8%: 86.2%, χ2=12.66, P= 0.001) and 5-year supraclavicular node recurrence free survival (97.7% :90.7%, χ2=9.98, P=0.002). However, axillary irradiation had no impact on 5-year axillary recurrence free survival (98.4%:96.1%, χ=0.74, P=0.389). In multivariate analysis, absence of radiotherapy (χ2=14.42, P=0.000), 10 or more positive axillary nodes (χ2=21.60, P=0.000), and T4 stage (χ2=10.79, P=0.001) were independent unfavorable prognostic factors for overall survival. Conclusions: Radiotherapy improves the overall survival of breast cancer patients with T3, T4 and/or four or more positive axillary nodes. The chest wall and supraclavicular nodal radiation should be given to this group of patients. (authors)

  15. Prognostic role of serum concentrations of high-sensitivity C-reactive protein in patients with metastatic colorectal cancer: results from the ITACa trial

    Science.gov (United States)

    Scarpi, Emanuela; Maltoni, Paolo; Dorizzi, Romolo M.; Passardi, Alessandro; Frassineti, Giovanni Luca; Cortesi, Pietro; Giannini, Maria Benedetta; Marisi, Giorgia; Amadori, Dino; Lucchesi, Alessandro

    2016-01-01

    Serum levels of C-reactive protein are (CRP) higher in patients with neoplastic conditions and numerous studies have been performed to clarify the etiologic and prognostic role of the high-sensitivity CRP (hs-CRP) in cancer. Our study was conducted on patients enrolled in the prospective randomized “Italian Trial in Advanced Colorectal Cancer (ITACa)” to assess hs-CRP levels and their impact on overall survival (OS) and progression-free survival (PFS). Serum samples from 132 ITACa patients were collected at baseline and 2 months after starting first-line chemotherapy. The supernatant was immediately transferred to cryovials and stored at −80°C. After thawing, hs-CRP was measured with the Cobas c501 analyzer. High levels of hs-CRP (≥ 13.1 mg/L) were associated with poorer median PFS (p < 0.0001) and OS (p < 0.0001) than low hs-CRP levels (< 13.1 mg/L). hs-CRP values in 107 patients were evaluated again after 2 months of therapy, revealing that patients with low hs-CRP levels in both baseline and second serum samples had the best median PFS and OS. Our study confirms the prognostic value of hs-CRP in patients with metastatic colorectal carcinoma. PMID:26848624

  16. Prognostic role of platelet to lymphocyte ratio in non-small cell lung cancers: A meta-analysis including 3,720 patients.

    Science.gov (United States)

    Zhao, Qing-Tao; Yuan, Zheng; Zhang, Hua; Zhang, Xiao-Peng; Wang, Hui-En; Wang, Zhi-Kang; Duan, Guo-Chen

    2016-07-01

    Platelet to lymphocyte ratio (PLR) was recently reported as a useful index in predicting the prognosis of lung cancer. However, the prognostic role of PLR in lung cancer remains controversial. The aim of this study was to evaluate the association between PLR and clinical outcome of lung cancer patients through a meta-analysis. Relevant literatures were retrieved from PubMed, Ovid, the Cochrane Library and Web of Science databases. Meta-analysis was performed using hazard ratio (HR) and 95% confidence intervals (CIs) as effect measures. A total of 5,314 patients from 13 studies were finally enrolled in the meta-analysis. The summary results showed that elevated PLR predicted poorer overall survival (OS) (HR: 1.526, 95%CI: 1.268-1.836, p 160 (HR: 1.842, 95%CI: 1.523-2.228, P  0.05) in patients with small cell lung cancer (SCLC).This meta-analysis result suggested that elevated PLR might be a predicative factor of poor prognosis for NSCLC patients. PMID:26915723

  17. The prognostic role of serum C-X-C chemokine receptor type 4 in patients with metastatic or recurrent colorectal cancer

    Science.gov (United States)

    Choi, Yoon Ji; Chang, Won Jin; Shin, Sang Won; Park, Kyong Hwa; Kim, Seung Tae; Kim, Yeul Hong

    2016-01-01

    Background C-X-C chemokine receptor type 4 (CXCR4) is involved in tumor progression including angiogenesis, metastasis, and survival. However, whether serum CXCR4 levels in metastatic or recurrent colorectal cancer have a prognostic role, have not been evaluated. Methods We analyzed serum samples from 55 patients with advanced colorectal cancer diagnosed between March 2008 and July 2011. Serum CXCR4 levels were quantified by a commercially available enzyme-linked immunosorbent assay (ELISA) kit. Results The median age of the patients was 62 years, and all patients received systemic chemotherapy of two or more lines. The median serum CXCR4 level was 283.47 pg/mL (range: 77.48–846.52). Patients with two or more metastatic sites, liver metastasis, or higher CA 19-9 level (>37 IU/mL) showed significantly higher levels of serum CXCR4 than patients without. The median overall survival (OS) of all patients was 19.53 months. OS was significantly longer in patients with lower CXCR4 levels (≤240.45 pg/mL) compared with those having higher CXCR4 levels (>240.45 pg/mL) (median OS: 26.50 vs 17.03 months, P=0.046). Univariate analysis showed that liver metastasis, no palliative surgery, and higher levels of CXCR4 (>240.45 pg/mL) had a significantly poor prognostic value with regard to OS (POS according to the level of CXCR4 expression. These findings suggest that serum CXCR4 levels may be a useful surrogate marker of clinical outcome in metastatic or recurrent colorectal cancer. PMID:27330310

  18. Prognostic Gene Expression Profiles in Breast Cancer

    DEFF Research Database (Denmark)

    Sørensen, Kristina Pilekær

    Each year approximately 4,800 Danish women are diagnosed with breast cancer. Several clinical and pathological factors are used as prognostic and predictive markers to categorize the patients into groups of high or low risk. Around 90% of all patients are allocated to the high risk group and...... clinical courses, and they may be useful as novel prognostic biomarkers in breast cancer. The aim of the present project was to predict the development of metastasis in lymph node negative breast cancer patients by RNA profiling. We collected and analyzed 82 primary breast tumors from patients who...... the time of event. Previous findings have shown that high expression of the lncRNA HOTAIR is correlated with poor survival in breast cancer. We validated this finding by demonstrating that high HOTAIR expression in our primary tumors was significantly associated with worse prognosis independent of...

  19. Prognostic DNA Methylation Markers for Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Siri H. Strand

    2014-09-01

    Full Text Available Prostate cancer (PC is the most commonly diagnosed neoplasm and the third most common cause of cancer-related death amongst men in the Western world. PC is a clinically highly heterogeneous disease, and distinction between aggressive and indolent disease is a major challenge for the management of PC. Currently, no biomarkers or prognostic tools are able to accurately predict tumor progression at the time of diagnosis. Thus, improved biomarkers for PC prognosis are urgently needed. This review focuses on the prognostic potential of DNA methylation biomarkers for PC. Epigenetic changes are hallmarks of PC and associated with malignant initiation as well as tumor progression. Moreover, DNA methylation is the most frequently studied epigenetic alteration in PC, and the prognostic potential of DNA methylation markers for PC has been demonstrated in multiple studies. The most promising methylation marker candidates identified so far include PITX2, C1orf114 (CCDC181 and the GABRE~miR-452~miR-224 locus, in addition to the three-gene signature AOX1/C1orf114/HAPLN3. Several other biomarker candidates have also been investigated, but with less stringent clinical validation and/or conflicting evidence regarding their possible prognostic value available at this time. Here, we review the current evidence for the prognostic potential of DNA methylation markers in PC.

  20. Prognostic DNA methylation markers for prostate cancer.

    Science.gov (United States)

    Strand, Siri H; Orntoft, Torben F; Sorensen, Karina D

    2014-01-01

    Prostate cancer (PC) is the most commonly diagnosed neoplasm and the third most common cause of cancer-related death amongst men in the Western world. PC is a clinically highly heterogeneous disease, and distinction between aggressive and indolent disease is a major challenge for the management of PC. Currently, no biomarkers or prognostic tools are able to accurately predict tumor progression at the time of diagnosis. Thus, improved biomarkers for PC prognosis are urgently needed. This review focuses on the prognostic potential of DNA methylation biomarkers for PC. Epigenetic changes are hallmarks of PC and associated with malignant initiation as well as tumor progression. Moreover, DNA methylation is the most frequently studied epigenetic alteration in PC, and the prognostic potential of DNA methylation markers for PC has been demonstrated in multiple studies. The most promising methylation marker candidates identified so far include PITX2, C1orf114 (CCDC181) and the GABRE~miR-452~miR-224 locus, in addition to the three-gene signature AOX1/C1orf114/HAPLN3. Several other biomarker candidates have also been investigated, but with less stringent clinical validation and/or conflicting evidence regarding their possible prognostic value available at this time. Here, we review the current evidence for the prognostic potential of DNA methylation markers in PC. PMID:25238417

  1. The prognostic role of mTOR and p-mTOR for survival in non-small cell lung cancer: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Lei Li

    Full Text Available The mammalian target of rapamycin (mTOR and phosphorylated mTOR (p-mTOR are potential prognostic markers and therapeutic targets for non-small cell lung cancer (NSCLC. However, the association between mTOR/p-mTOR expression and NSCLC patients' prognosis remains controversial. Thus, a meta-analysis of existing studies evaluating the prognostic role of mTOR/p-mTOR expression for NSCLC was conducted.A systemically literature search was performed via Pubmed, Embase, Medline as well as CNKI (China National Knowledge Infrastructure. Studies were included that reported the hazard ratio (HR and 95%CI for the association between mTOR/p-mTOR expression and NSCLC patients' survival. Random-effects model was used to pool HRs.Ten eligible studies were included in this meta-analysis, with 4 about m-TOR and 7 about p-mTOR. For mTOR, the pooled HR of overall survival (OS was 1.00 (95%CI 0.5 to 1.99 by univariate analysis and 1.22 (95%CI 0.53 to 2.82 by multivariate analysis. For p-mTOR, the pooled HR was 1.39 (95%CI 0.97 to 1.98 by univariate analysis and 1.42 (95%CI 0.56 to 3.60 by multivariate analysis.The results indicated that no statistically significant association was found between mTOR/p-mTOR expression and NSCLC patients' prognosis.

  2. Prognostic value of the neutrophil to lymphocyte ratio in lung cancer: A meta-analysis

    OpenAIRE

    Yin, Yongmei; Wang, Jun; Wang, Xuedong; Gu, Lan; Pei, Hao; Kuai, Shougang; Zhang, Yingying; Shang, Zhongbo

    2015-01-01

    Recently, a series of studies explored the correlation between the neutrophil to lymphocyte ratio and the prognosis of lung cancer. However, the current opinion regarding the prognostic role of the neutrophil to lymphocyte ratio in lung cancer is inconsistent. We performed a meta-analysis of published articles to investigate the prognostic value of the neutrophil to lymphocyte ratio in lung cancer. The hazard ratio (HR) and its 95% confidence interval (CI) were calculated. An elevated neutrop...

  3. The prognostic role of PRUNE2 in leiomyosarcoma

    Institute of Scientific and Technical Information of China (English)

    Lin-Ru Zhao; Wei Tian; Guo-Wen Wang; Ke-Xin Chen; Ji-Long Yang

    2013-01-01

    PRUNE2 plays an important role in regulating tumor celldifferentiation, proliferation, and invasiveness in neuroblastoma. Our previous study revealed that PRUNE2/OBSCN two-gene relative expression classifer accurately differentiated leiomyosarcoma from gastrointestinal stromal tumor. However, the association between PRUNE2 expression and prognosis in leiomyosarcoma is poorly understood. In this study, we evaluated the prognostic role of PRUNE2 in leiomyosarcoma. PRUNE2 expression was detected using immunohistochemistry in 30 formalin-fixed, paraffin-embedded leiomyosarcoma tissues from MD Anderson Cancer Center, and high expression was detected in 36.7%(11/30) of the samples. To validate these results, immunohistochemistry was performed on another cohort of 45 formalin-fixed, paraffin-embedded leiomyosarcoma tissues from Tianjin Medical University Cancer Institute & Hospital, and high PRUNE2 protein expression was detected in 37.8%(17/45) of the samples. Moreover, elevated PRUNE2 expression was significantly associated with tumor size (P = 0.03) and hemorrhage/cyst (P = 0.014), and was an independent favorable prognostic factor for overal survival in leiomyosarcoma patients from Tianjin Medical University Cancer Institute & Hospital (P < 0.05). These data suggest that increased PRUNE2 protein expression may serve as a favorable prognostic marker in human leiomyosarcoma.

  4. PROGNOSTIC FACTORS OF SURVIVAL IN RENAL CANCER

    Directory of Open Access Journals (Sweden)

    A. V. Seriogin

    2014-08-01

    Full Text Available The purpose of the study was to reveal the independent anatomic, histological, and clinical factors of cancer-specific survival in patients with renal-cell carcinoma (RCC. For this, the authors retrospectively analyzed their experience with radical surgical treatments in 73 RCC patients operated on at the Department of Urology and Surgical Andrology, Russian Medical Academy of Postgraduate Education, from January 1, 1999 to December 31, 2004; their outcomes have become known by the present time. There was a statistically significant correlation of cancer-specific survival with its parameters, such as pathological stage of a tumor, its maximum pathological size, differentiation grade, involvement of regional lymph nodes, venous tumor thrombosis, level of thrombocytosis, and degree of the clinical symptoms of the disease. Multivariate analysis of survival in RCC in relation to the prognostic factors could reveal odd ratios for the limit values of significant prognostic factors. The statistically significant prognostic values established in the present study, as well as the molecular factors the implication of which is being now investigated can become in future an effective addition to the TNM staging system to define indications for certain treatments and to predict survival in RCC  

  5. Computational prognostic indicators for breast cancer

    Directory of Open Access Journals (Sweden)

    Yang X

    2014-07-01

    Full Text Available Xinan Yang,1 Xindi Ai,2 John M Cunningham1 1Section of Hematology/Oncology, Department of Pediatrics, and Comer Children's Hospital, The University of Chicago, Chicago, IL, USA; 2Department of Biological Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD, USA Abstract: Breast cancer remains the leading cause of cancer-related mortality in women. Comprehensive genomics, proteomics, and metabolomics studies are emerging that offer an opportunity to model disease biology, prognosis, and response to specific therapies. Although many biomarkers have been identified through advances in data mining techniques, few have been applied broadly to make patient-specific decisions. Here, we review a selection of breast cancer prognostic indicators and their implications. Our goal is to provide clinicians with a general evaluation of emerging computational methodologies for outcome prediction. Keywords: computational model, precision prognosis, tumor

  6. Prognostic significance of detection of microscopic peritoneal disease in colorectal cancer: a systematic review.

    LENUS (Irish Health Repository)

    Mohan, Helen M

    2013-06-01

    Free intraperitoneal tumour cells are an independent indicator of poor prognosis, and are encorporated in current staging systems in upper gastrointestinal cancers, but not colorectal cancer. This systematic review aimed to evaluate the role and prognostic significance of positive peritoneal lavage in colorectal cancer.

  7. Insights into orphan nuclear receptors as prognostic markers and novel therapeutic targets for breast cancer

    OpenAIRE

    Reidun eAesoy; Colin D Clyne; Ashwini eChand

    2015-01-01

    The roles of orphan nuclear receptors in breast cancer development and progression are not well understood. In this review, we correlate orphan nuclear receptor expression in breast cancer tumour subtypes with patient outcomes and provide an overview of functional evidence that identifies candidate orphan nuclear receptors as prognostic markers or as therapeutic targets in breast cancer.

  8. Prognostic Role of Circulating Tumor Cells during Induction Chemotherapy Followed by Curative Surgery Combined with Postoperative Radiotherapy in Patients with Locally Advanced Oral and Oropharyngeal Squamous Cell Cancer.

    Directory of Open Access Journals (Sweden)

    Johanna Inhestern

    Full Text Available The prognostic role of circulating tumor cells (CTCs after induction chemotherapy using docetaxel, cisplatin and fluorouracil (TPF prior to surgery and adjuvant (chemoradiation in locally advanced oral squamous cell cancer (OSCC was evaluated.In this prospective study, peripheral blood samples from 40 patients of the phase II study TISOC-1 (NCT01108042 with OSCC before, during, and after treatment were taken. CTCs were quantified using laser scanning cytometry of anti- epithelial cell adhesion molecule-stained epithelial cells. Their detection was correlated with clinical risk factors, recurrence-free (RFS and overall survival (OS.Before starting the treatment CTCs were detected in 32 of 40 patients (80%. The median number at baseline was 3295 CTCs/ml. The median maximal number of CTCs during treatment was 5005 CTCs/ml. There was a significant increase of CTCs before postoperative radiotherapy compared to baseline before 1st cycle of IC (p = 0.011, 2nd cycle of IC (p = 0.001, 3rd cycle of IC (p = 0.004, and before surgery (p = 0.002, but not compared to end of therapy (p = 0.118. CTCs at baseline >median was also associated to risk of recurrence (p = 0.014. Maximal CTCs during therapy >median was more frequently observed in tumors of the oral cavity (p=0.022 and related to higher risk of death during follow-up (p = 0.028. Patients with CTCs at baseline >median value had significant lower RFS than patients with CTCs at baseline median during the complete course of therapy had a significantly lower OS than patients with values prognostic markers for OSCC when treated by TPF induction chemotherapy, surgery, and postoperative (chemoradiation.

  9. DNA Repair Gene Patterns as Prognostic and Predictive Factors in Molecular Breast Cancer Subtypes

    OpenAIRE

    Santarpia, Libero; Iwamoto, Takayuki; Di Leo, Angelo; Hayashi, Naoki; Bottai, Giulia; Stampfer, Martha; André, Fabrice; Turner, Nicholas C.; Symmans, W Fraser; Hortobágyi, Gabriel N.; Pusztai, Lajos; Bianchini, Giampaolo

    2013-01-01

    DNA repair pathways can enable tumor cells to survive DNA damage induced by chemotherapy and thus provide prognostic and/or predictive value. In this study, the authors sought to assess the differential expression, bimodal distribution, and prognostic and predictive role of DNA repair genes in individual breast cancer molecular subtypes including estrogen receptor-positive/ HER2-negative, estrogen receptor-negative/HER2-negative, and HER2-positive cancers. The predictive value of DNA repair g...

  10. Prognostic significance of interleukin 17 in cancer: a meta-analysis

    OpenAIRE

    Zhang, Xiao; Weng, Wenhao; Xu, Wen; Wang, Yulan; Yu, Wenjun; Tang, Xun; Ma, Lifang; Pan, Qiuhui; Wang, Jiayi; Sun, Fenyong

    2014-01-01

    The prognostic value of Interleukin 17 (IL-17) in cancer patients is currently under debate and remains inconclusive. We performed a systematic review and meta-analysis to evaluate the role of IL-17 as a prognostic marker in cancer. Hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were combined to measure the effective value of IL-17 expression on prognosis. Nineteen eligible studies enrolling 2390 patients were identified. We found expression of IL-17 was not significantl...

  11. Nottingham Prognostic Index in Triple-Negative Breast Cancer: a reliable prognostic tool?

    International Nuclear Information System (INIS)

    A breast cancer prognostic tool should ideally be applicable to all types of invasive breast lesions. A number of studies have shown histopathological grade to be an independent prognostic factor in breast cancer, adding prognostic power to nodal stage and tumour size. The Nottingham Prognostic Index has been shown to accurately predict patient outcome in stratified groups with a follow-up period of 15 years after primary diagnosis of breast cancer. Clinically, breast tumours that lack the expression of Oestrogen Receptor, Progesterone Receptor and Human Epidermal growth factor Receptor 2 (HER2) are identified as presenting a 'triple-negative' phenotype or as triple-negative breast cancers. These poor outcome tumours represent an easily recognisable prognostic group of breast cancer with aggressive behaviour that currently lack the benefit of available systemic therapy. There are conflicting results on the prevalence of lymph node metastasis at the time of diagnosis in triple-negative breast cancer patients but it is currently accepted that triple-negative breast cancer does not metastasize to axillary nodes and bones as frequently as the non-triple-negative carcinomas, favouring instead, a preferentially haematogenous spread. Hypothetically, this particular tumour dissemination pattern would impair the reliability of using Nottingham Prognostic Index as a tool for triple-negative breast cancer prognostication. The present study tested the effectiveness of the Nottingham Prognostic Index in stratifying breast cancer patients of different subtypes with special emphasis in a triple-negative breast cancer patient subset versus non- triple-negative breast cancer. We demonstrated that besides the fact that TNBC disseminate to axillary lymph nodes as frequently as luminal or HER2 tumours, we also showed that TNBC are larger in size compared with other subtypes and almost all grade 3. Additionally, survival curves demonstrated that these prognostic factors are

  12. Prognostic significance of miR-205 in endometrial cancer.

    Directory of Open Access Journals (Sweden)

    Mihriban Karaayvaz

    Full Text Available PURPOSE: microRNAs have emerged as key regulators of gene expression, and their altered expression has been associated with tumorigenesis and tumor progression. Thus, microRNAs have potential as both cancer biomarkers and/or potential novel therapeutic targets. Although accumulating evidence suggests the role of aberrant microRNA expression in endometrial carcinogenesis, there are still limited data available about the prognostic significance of microRNAs in endometrial cancer. The goal of this study is to investigate the prognostic value of selected key microRNAs in endometrial cancer by the analysis of archival formalin-fixed paraffin-embedded tissues. EXPERIMENTAL DESIGN: Total RNAs were extracted from 48 paired normal and endometrial tumor specimens using Trizol based approach. The expression of miR-26a, let-7g, miR-21, miR-181b, miR-200c, miR-192, miR-215, miR-200c, and miR-205 were quantified by real time qRT-PCR expression analysis. Targets of the differentially expressed miRNAs were quantified using immunohistochemistry. Statistical analysis was performed by GraphPad Prism 5.0. RESULTS: The expression levels of miR-200c (P<0.0001 and miR-205 (P<0.0001 were significantly increased in endometrial tumors compared to normal tissues. Kaplan-Meier survival analysis revealed that high levels of miR-205 expression were associated with poor patient overall survival (hazard ratio, 0.377; Logrank test, P = 0.028. Furthermore, decreased expression of a miR-205 target PTEN was detected in endometrial cancer tissues compared to normal tissues. CONCLUSION: miR-205 holds a unique potential as a prognostic biomarker in endometrial cancer.

  13. Chromosomal instability as a prognostic marker in cervical cancer

    International Nuclear Information System (INIS)

    Cervical cancer is the third most common cancer in women globally, and despite treatment, distant metastasis and nodal recurrence will still develop in approximately 30% of patients. The ability to predict which patients are likely to experience distant relapse would allow clinicians to better tailor treatment. Previous studies have investigated the role of chromosomal instability (CIN) in cancer, which can promote tumour initiation and growth; a hallmark of human malignancies. In this study, we sought to examine the published CIN70 gene signature in a cohort of cervical cancer patients treated at the Princess Margaret (PM) Cancer Centre and an independent cohort of The Cancer Genome Atlas (TCGA) cervical cancer patients, to determine if this CIN signature associated with patient outcome. Cervical cancer samples were collected from 79 patients, treated between 2000–2007 at the PM, prior to undergoing curative chemo-radiation. Total RNA was extracted from each patient sample and analyzed using the GeneChip Human Genome U133 Plus 2.0 array (Affymetrix). High CIN70 scores were significantly related to increased chromosomal alterations in TCGA cervical cancer patients, including a higher percentage of genome altered and a higher number of copy number alterations. In addition, this same CIN70 signature was shown to be predictive of para-aortic nodal relapse in the PM Cancer Centre cohort. These findings demonstrate that chromosomal instability plays an important role in cervical cancer, and is significantly associated with patient outcome. For the first time, this CIN70 gene signature provided prognostic value for patients with cervical cancer

  14. PROGNOSTIC SIGNIFICANCE OF COMPLETE BLOOD COUNT IN BREAST CANCER PATIENTS

    OpenAIRE

    Preeti Chauhan, Dr. Ritu Yadav*, Vivek Kaushal, Preeti Beniwal

    2016-01-01

    Objective: Breast carcinoma is the most common cancer worldwide. The incidence and mortality rate is increasing in developing countries as compare to developed countries. The aim of this study was to assess complete blood count of the breast cancer patients to determine their prognostic values during the different courses of chemotherapy treatment.  Methods: In the present study, two hundred breast cancer patients were selected to study prognostic significance of peripheral blood of ...

  15. Prognostic role of indoleamine 2,3-dioxygenase in endometrial carcinoma

    NARCIS (Netherlands)

    de Jong, Renske A; Kema, Ido P; Boerma, Annemarie; Boezen, Hendrika; van der Want, Johannes J L; Gooden, Marloes J M; Hollema, Harmen; Nijman, Hans W

    2012-01-01

    Objective. Indoleamine-2,3-dioxygenase (IDO) suppresses the function of T-lymphocytes and is an important immune escape mechanism for cancer. Therefore, it is to be expected that IDO influences prognosis of cancer patients. This study aimed to investigate the prognostic role of IDO expression in a l

  16. Prognostic factors in ovarian cancer : current evidence and future prospects

    NARCIS (Netherlands)

    Crijns, APG; Boezen, HM; Schouten, JP; Arts, HJG; Hofstra, RMW; Willemse, PHB; de Vries, EGE; van der Zee, AGJ

    2003-01-01

    In ovarian cancer, translational research on the prognostic impact of molecular biological factors has until now not led to clinical implementation of any of these factors. This is partly due to the often conflicting results of different prognostic factor studies on the same molecular biological fac

  17. Pretreatment serum albumin: a prognostic indicator of survival in oral cancer

    OpenAIRE

    Saurabh Bobdey; Aanchal Jain; Jignasa Sathwara; Ganesh B

    2016-01-01

    Background: Malnutrition has been recognized as a poor prognostic indicator for cancer. In recent years, the role of serum albumin as a predictor of survival in cancer has received considerable attention. Therefore, the present study was carried out to investigate whether the pretreatment serum albumin can predict the prognosis of patients with oral cancer. Methods: Medical records of 433 pathologically proven oral cancer patients diagnosed and treated from 01st January 2006 to 31st Decemb...

  18. The Prognostic and Predictive Value of Soluble Type IV Collagen in Colorectal Cancer

    DEFF Research Database (Denmark)

    Rolff, Hans Christian; Christensen, Ib Jarle; Vainer, Ben;

    2016-01-01

    validation set, respectively. The prognostic impact was present both in patients with metastatic and nonmetastatic disease. The predictive value of the marker was investigated in stage II and III patients. In the training set, type IV collagen was prognostic both in the subsets of patients receiving and not...... receiving adjuvant antineoplastic therapy. However, in the validation set, the prognostic effect of the marker vanished when looking at patients who received adjuvant antineoplatic therapy (HR 0.90; 95% CI, 0.42-1.93) but was still present in the group not receiving adjuvant chemotherapy (HR 2.88; 95% CI, 1.......98-4.21). CONCLUSIONS: The results indicate clinical validity of type IV collagen as a prognostic biomarker in colorectal cancer, although the suggested predictive role of the marker should be validated. Clin Cancer Res; 22(10); 2427-34. ©2015 AACR....

  19. Prognostic stratification of colorectal cancer patients: current perspectives

    International Nuclear Information System (INIS)

    Tumor staging according to the American Joint Committee on Cancer/Union for International Cancer Control tumor, node, metastasis (TNM) system is currently regarded as the standard for staging of patients with colorectal cancer. This system provides the strongest prognostic information for patients with early stage disease and those with advanced disease. For patients with intermediate levels of disease, it is less able to predict disease outcome. Therefore, additional prognostic markers are needed to improve the management of affected patients. Ideal markers are readily assessable on hematoxylin and eosin-stained tumor slides, and in this way are easily applicable worldwide. This review summarizes the histological features of colorectal cancer that can be used for prognostic stratification. Specifically, we refer to the different histological variants of colorectal cancer that have been identified, each of these variants carrying distinct prognostic significance. Established markers of adverse outcomes are lymphatic and venous invasion, as well as perineural invasion, but underreporting still occurs in the routine setting. Tumor budding and tumor necrosis are recent advances that may help to identify patients at high risk for recurrence. The prognostic significance of the antitumor inflammatory response has been known for quite a long time, but a lack of standardization prevented its application in routine pathology. However, scales to assess intra- and peritumoral inflammation have recently emerged, and can be expected to strengthen the prognostic significance of the pathology report

  20. Prognostic factors in the estimation of HIFU treatment efficiency in patients with localized prostate cancer

    OpenAIRE

    Popkov V.M.; Fomkin R.N.; Blyumberg B.I.

    2013-01-01

    Research objective: To study the role of prognostic factors in the estimation of risk development of recurrent prostate cancer after treatment by high-intensive focused ultrasound (HIUF). Objects and Research Methods: The research has included 102 patients with morphologically revealed localized prostate cancer by biopsy. They have been on treatment in Clinic of Urology of the Saratov Clinical Hospital n.a. S. R. Mirotvortsev. 102 sessions of initial operative treatment of prostate cancer by ...

  1. An Algorithm for Creating Prognostic Systems for Cancer.

    Science.gov (United States)

    Chen, Dechang; Wang, Huan; Sheng, Li; Hueman, Matthew T; Henson, Donald E; Schwartz, Arnold M; Patel, Jigar A

    2016-07-01

    The TNM staging system is universally used for classification of cancer. This system is limited since it uses only three factors (tumor size, extent of spread to lymph nodes, and status of distant metastasis) to generate stage groups. To provide a more accurate description of cancer and thus better patient care, additional factors or variables should be used to classify cancer. In this paper we propose a hierarchical clustering algorithm to develop prognostic systems that classify cancer according to multiple prognostic factors. This algorithm has many potential applications in augmenting the data currently obtained in a staging system by allowing more prognostic factors to be incorporated. The algorithm clusters combinations of prognostic factors that are formed using categories of factors. The dissimilarity between two combinations is determined by the area between two corresponding survival curves. Groups from cutting the dendrogram and survival curves of the individual groups define our prognostic systems that classify patients using survival outcomes. A demonstration of the proposed algorithm is given for patients with breast cancer from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute. PMID:27189622

  2. Prognostic Value of Cancer Stem Cells Markers in Triple-Negative Breast Cancer

    Directory of Open Access Journals (Sweden)

    Francesca Collina

    2015-01-01

    Full Text Available Triple-negative breast cancer (TNBC has a significant clinical relevance of being associated with a shorter median time to relapse and death and does not respond to endocrine therapy or other available targeted agents. Increased aggressiveness of this tumor, as well as resistance to standard drug therapies, may be associated with the presence of stem cell populations within the tumor. Several stemness markers have been described for the various histological subtypes of breast cancer, such as CD44, CD24, CD133, ALDH1, and ABCG2. The role of these markers in breast cancer is not clear yet and above all there are conflicting opinions about their real prognostic value. To investigate the role of CSCs markers in TNBC cancerogenesis and tumor progression, we selected 160 TNBCs samples on which we detected protein expression of CD44, CD24, CD133, ALDH1, and ABCG2 by immunohistochemistry. Our results highlighted a real prognostic role only for CD44 in TNBCs. All other CSCs markers do not appear to be related to the survival of TNBC patients. In conclusion, despite the fact that the presence of the cancer stem cells in the tumor provides important information on its potential aggressiveness, today their detection by immunohistochemistry is not sufficient to confirm their role in carcinogenesis, because specific markers probably are not yet identified.

  3. Cathepsin b: a potential prognostic marker for inflammatory breast cancer

    Directory of Open Access Journals (Sweden)

    Cavallo-Medved Dora

    2011-01-01

    Full Text Available Abstract Background Inflammatory breast cancer (IBC is the most aggressive form of breast cancer. In non-IBC, the cysteine protease cathepsin B (CTSB is known to be involved in cancer progression and invasion; however, very little is known about its role in IBC. Methods In this study, we enrolled 23 IBC and 27 non-IBC patients. All patient tissues used for analysis were from untreated patients. Using immunohistochemistry and immunoblotting, we assessed the levels of expression of CTSB in IBC versus non-IBC patient tissues. Previously, we found that CTSB is localized to caveolar membrane microdomains in cancer cell lines including IBC, and therefore, we also examined the expression of caveolin-1 (cav-1, a structural protein of caveolae in IBC versus non-IBC tissues. In addition, we tested the correlation between the expression of CTSB and cav-1 and the number of positive metastatic lymph nodes in both patient groups. Results Our results revealed that CTSB and cav-1 were overexpressed in IBC as compared to non-IBC tissues. Moreover, there was a significant positive correlation between the expression of CTSB and the number of positive metastatic lymph nodes in IBC. Conclusions CTSB may initiate proteolytic pathways crucial for IBC invasion. Thus, our data demonstrate that CTSB may be a potential prognostic marker for lymph node metastasis in IBC.

  4. Prognostic scores in brain metastases from breast cancer

    OpenAIRE

    Astner Sabrina T; Marienhagen Kirsten; Nieder Carsten; Molls Michael

    2009-01-01

    Abstract Background Prognostic scores might be useful tools both in clinical practice and clinical trials, where they can be used as stratification parameter. The available scores for patients with brain metastases have never been tested specifically in patients with primary breast cancer. It is therefore unknown which score is most appropriate for these patients. Methods Five previously published prognostic scores were evaluated in a group of 83 patients with brain metastases from breast can...

  5. Prognostic stratification of colorectal cancer patients: current perspectives

    Directory of Open Access Journals (Sweden)

    Schneider NI

    2014-07-01

    Full Text Available Nora I Schneider, Cord LangnerInstitute of Pathology, Medical University of Graz, Graz, AustriaAbstract: Tumor staging according to the American Joint Committee on Cancer/Union for International Cancer Control tumor, node, metastasis (TNM system is currently regarded as the standard for staging of patients with colorectal cancer. This system provides the strongest prognostic information for patients with early stage disease and those with advanced disease. For patients with intermediate levels of disease, it is less able to predict disease outcome. Therefore, additional prognostic markers are needed to improve the management of affected patients. Ideal markers are readily assessable on hematoxylin and eosin-stained tumor slides, and in this way are easily applicable worldwide. This review summarizes the histological features of colorectal cancer that can be used for prognostic stratification. Specifically, we refer to the different histological variants of colorectal cancer that have been identified, each of these variants carrying distinct prognostic significance. Established markers of adverse outcomes are lymphatic and venous invasion, as well as perineural invasion, but underreporting still occurs in the routine setting. Tumor budding and tumor necrosis are recent advances that may help to identify patients at high risk for recurrence. The prognostic significance of the antitumor inflammatory response has been known for quite a long time, but a lack of standardization prevented its application in routine pathology. However, scales to assess intra- and peritumoral inflammation have recently emerged, and can be expected to strengthen the prognostic significance of the pathology report.Keywords: colorectal cancer, lymphatic invasion, blood-vessel invasion, perineural invasion, tumor budding, tumor necrosis

  6. Diagnostic Value and Prognostic Significance of Pleural C-Reactive Protein in Lung Cancer Patients with Malignant Pleural Effusions

    OpenAIRE

    Park, Do-Sim; Kim, Dong; Hwang, Ki-Eun; Hwang, Yu-Ri; Park, Chul; Seol, Chang-Hwan; Cho, Kyung-Hwa; Kim, Byoung-Ryun; Park, Seong-Hoon; Jeong, Eun-Taik; Kim, Hak-Ryul

    2013-01-01

    Purpose C-reactive protein (CRP) has been implicated in various inflammatory and advanced malignant states. Increased serum CRP (s-CRP) levels have been shown to be associated with independent prognostic factors for survival in patients with advanced lung cancer. However, only few studies have focused on the role of CRP in pleural effusions. This study aimed to evaluate the diagnostic and prognostic value of pleural CRP (p-CRP) in lung cancer patients with malignant pleural effusion (MPE). Ma...

  7. High-throughput microRNA (miRNAs arrays unravel the prognostic role of MiR-211 in pancreatic cancer.

    Directory of Open Access Journals (Sweden)

    Elisa Giovannetti

    independent factor of poor prognosis (hazard ratio 2.3, P = 0.03 after adjusting for all the factors influencing outcome. CONCLUSIONS/SIGNIFICANCE: Through comprehensive microarray analysis and PCR validation we identified miR-211 as a prognostic factor in resected PDAC. These results prompt further prospective studies and research on the biological role of miR-211 in PDAC.

  8. Midkine: A Novel Prognostic Biomarker for Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Jono, Hirofumi, E-mail: hjono@fc.kuh.kumamoto-u.ac.jp; Ando, Yukio [Department of Diagnostic Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556 (Japan)

    2010-04-20

    Since diagnosis at an early stage still remains a key issue for modern oncology and is crucial for successful cancer therapy, development of sensitive, specific, and non-invasive tumor markers, especially, in serum, is urgently needed. Midkine (MK), a plasma secreted protein, was initially identified in embryonal carcinoma cells at early stages of retinoic acid-induced differentiation. Multiple studies have reported that MK plays important roles in tumor progression, and is highly expressed in various malignant tumors. Because increased serum MK concentrations also have been reported in patients with various tumors, serum MK may have the potential to become a very useful tumor marker. Here, we review and discuss the possibility and usefulness of MK as a novel tumor marker.

  9. Prognostic significance of aberrantly silenced ANPEP expression in prostate cancer

    DEFF Research Database (Denmark)

    Sørensen, Karina Dalsgaard; Abildgaard, Mette Opstrup; Haldrup, Christa;

    2013-01-01

    Background:Novel biomarkers for prostate cancer (PC) are urgently needed. This study investigates the expression, epigenetic regulation, and prognostic potential of ANPEP in PC.Methods:Aminopeptidase N (APN; encoded by ANPEP) expression was analysed by immunohistochemistry using tissue microarrays...

  10. Multivariate Regression Analysis of Prognostic Factors in Colorectal Cancer

    Institute of Scientific and Technical Information of China (English)

    YANGZuli; WANGJianping; WANGLei; DONGWenguang; HUANGYihua; QINJianzhang; ZHANWenhua

    2003-01-01

    Objective: To evaluate the relationship between clinicopathologic features and prognosis of col-orectal cancer after surgical treatment. Methods: The relationship between clinicopathological character-istics and prognosis of 941 patients with colorectal cancer after surgical treatment were investigated by univariate and multivariate analysis. Results: The overall 3- and 5-year survival rates of patients withcolorectal cancer after surgical treatment were 63.2% and 60.8% respectively with a median survival of 1841 days. Univariate analysis revealed that such factors as gross findings, degree of differentiation, depth of infiltration, nodal and distant metastasis and neoplastic intestinal obstruction were correlated with the survival rate. Dukes stages, gross tumor configuration, intramural spread and differentiation degree were shown to be available independent prognostic factors by multivariate analysis. Conclusion: Dukes stage,as the most important available independent prognostic factor for colorectal cancer (P<0.0005), can be used to assess the postoperative survival.

  11. Prognostic scores in brain metastases from breast cancer

    Directory of Open Access Journals (Sweden)

    Astner Sabrina T

    2009-04-01

    Full Text Available Abstract Background Prognostic scores might be useful tools both in clinical practice and clinical trials, where they can be used as stratification parameter. The available scores for patients with brain metastases have never been tested specifically in patients with primary breast cancer. It is therefore unknown which score is most appropriate for these patients. Methods Five previously published prognostic scores were evaluated in a group of 83 patients with brain metastases from breast cancer. All patients had been treated with whole-brain radiotherapy with or without radiosurgery or surgical resection. In addition, it was tested whether the parameters that form the basis of these scores actually have a prognostic impact in this biologically distinct group of brain metastases patients. Results The scores that performed best were the recursive partitioning analysis (RPA classes and the score index for radiosurgery (SIR. However, disagreement between the parameters that form the basis of these scores and those that determine survival in the present group of patients and many reported data from the literature on brain metastases from breast cancer was found. With the four statistically significant prognostic factors identified here, a 3-tiered score can be created that performs slightly better than RPA and SIR. In addition, a 4-tiered score is also possible, which performs better than the three previous 4-tiered scores, incl. graded prognostic assessment (GPA score and basic score for brain metastases (BSBM. Conclusion A variety of prognostic models describe the survival of patients with brain metastases from breast cancer to a more or less satisfactory degree. However, the standard brain metastases scores might not fully appreciate the unique biology and time course of this disease, e.g., compared to lung cancer. It appears possible that inclusion of emerging prognostic factors will improve the results and allow for development and validation

  12. Predictive and prognostic effect of CD133 and cancer-testis antigens in stage Ib-IIIA non-small cell lung cancer

    OpenAIRE

    SU, CHUNXIA; Xu, Ying; Xuefei LI; Ren, Shengxiang; Zhao, Chao; Hou, Likun; Ye, Zhiwei; Zhou, Caicun

    2015-01-01

    CD133 and cancer-testis antigens (CTAs) may be potential predicted markers of adjuvant chemotherapy or immune therapy, and they may be the independent prognostic factor of NSCLC. Nowadays, there is still no predictive biomarker identified for the use of adjuvant chemotherapy in non-small cell lung cancer (NSCLC) patients. To clarify the role of CD133 and CTAs as a predictive marker for adjuvant chemotherapy or prognostic factors of overall survival, we performed a retrospective study in 159 s...

  13. Prognostic role of microRNA-150 in various carcinomas: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Wang W

    2016-03-01

    Full Text Available Wei Wang, Xinshuai Wang, Yali Zhang, Dan Wang, Hui Gao, Lijuan Wang, Shegan Gao Henan Key Laboratory of Cancer Epigenetics, Cancer Institute, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, Henan, People’s Republic of China Objective: MicroRNA-150 (miR-150 was revealed to be an attractive prognostic biomarker in recent studies. However, the prognostic significance of miR-150 expression in cancer remains inconclusive. The aim of this study was to summarize the global predicting role of miR-150 in survival in patients with various carcinomas.Methods: Eligible studies were identified through multiple search strategies. Data were extracted from the studies by investigating the relationship between miR-150 expression and survival in patients with cancer. A meta-analysis of the hazard ratio (HR was then performed to evaluate the prognostic role of miR-150 in different tumors. Pooled HRs of miR-150 for overall survival and progression-free survival were calculated to measure the effect of miR-150 expression on prognosis.Results: This meta-analysis included nine published studies concerning various carcinomas. Our results indicate that an elevated miR-150 expression is associated with an enhanced overall survival in the digestive tract cancer subgroup (HR =0.57, 95% confidence interval [CI]: 0.37–0.90 and a poor progression-free survival in various cancers (HR =3.08, 95% CI: 2.00–4.75.Conclusion: miR-150 may have the potential to become a new useful prognostic factor to monitor cancer prognosis and progression. However, given the current insufficient relevant data, further clinical studies are needed. Keywords: microRNA-150, carcinomas, prognosis, meta-analysis

  14. Overexpression of MMP Family Members Functions as Prognostic Biomarker for Breast Cancer Patients: A Systematic Review and Meta-Analysis

    OpenAIRE

    Ren, Fanghui; Tang, Ruixue; Zhang, Xin; Madushi, Wickramaarachchi Mihiranganee; Luo, Dianzhong; Dang, Yiwu; Li, Zuyun; WEI, KANGLAI; Chen, Gang

    2015-01-01

    Background Matrix metalloproteinases (MMPs) are regarded to be relevant to the prognosis of breast cancer. Numerous studies have confirmed the association between MMPs and tumor growth, invasion and metastasis in breast cancer. However, their prognostic values for survival in patients with breast cancer remain controversial. Hence, a meta-analysis was performed to clarify a more accurate estimation of the role of MMPs on prognosis of breast cancer patients. Method A systemic electronic search...

  15. The prognostic role of HER2 expression in ductal breast carcinoma in situ (DCIS); a population-based cohort study

    OpenAIRE

    Borgquist, Signe; Zhou, Wenjing; Jirström, Karin; Amini, Rose-Marie; Sollie, Thomas; Sørlie, Therese; Blomqvist, Carl; Butt, Salma; Wärnberg, Fredrik

    2015-01-01

    Abstract Background HER2 is a well-established prognostic and predictive factor in invasive breast cancer. The role of HER2 in ductal breast carcinoma in situ (DCIS) is debated and recent data have suggested that HER2 is mainly related to in situ recurrences. Our aim was to study HER2 as a prognostic factor in a large population based cohort of DCIS with long-term follow-up. Methods ...

  16. Important prognostic factors for the long-term survival of lung cancer subjects in Taiwan

    International Nuclear Information System (INIS)

    This study used a large-scale cancer database in determination of prognostic factors for the survival of lung cancer subjects in Taiwan. Total of 24,910 subjects diagnosed with lung cancer was analysed. Survival estimates by Kaplan-Meier methods. Cox proportional-hazards model estimated the death risk (hazard ratio (HR)) for various prognostic factors. The prognostic indicators associated with a higher risk of lung cancer deaths are male gender (males versus females; HR = 1.07, 95% confidence intervals (CI): 1.03–1.11), males diagnosed in later periods (shown in 1991–1994 versus 1987–1990; HR = 1.13), older age at diagnosis, large cell carcinoma (LCC)/small cell carcinoma (SCC), and supportive care therapy over chemotherapy. The overall 5-year survival rate for lung cancer death was significantly poorer for males (21.3%) than females (23.6%). Subjects with squamous cell carcinoma (SQCC) and treatment by surgical resection alone had better prognosis. We find surgical resections to markedly increase 5-year survival rate from LCC, decreased risk of death from LCC, and no improved survival from SCC. Gender and clinical characteristics (i.e. diagnostic period, diagnostic age, histological type and treatment modality) play important roles in determining lung cancer survival

  17. Histopathological prognostic factor comparison of endometrial cancer patients in a tertiary hospital in India

    Directory of Open Access Journals (Sweden)

    P. Swarna Latha

    2014-02-01

    Conclusions: This study highlights the prognostic characteristics of endometrial cancer patients with most of them presenting in early stages thereby having a good prognostic outcome. [Int J Reprod Contracept Obstet Gynecol 2014; 3(1.000: 102-104

  18. Prognostic Factors for Distress After Genetic Testing for Hereditary Cancer.

    Science.gov (United States)

    Voorwinden, Jan S; Jaspers, Jan P C

    2016-06-01

    The psychological impact of an unfavorable genetic test result for counselees at risk for hereditary cancer seems to be limited: only 10-20 % of counselees have psychological problems after testing positive for a known familial mutation. The objective of this study was to find prognostic factors that can predict which counselees are most likely to develop psychological problems after presymptomatic genetic testing. Counselees with a 50 % risk of BRCA1/2 or Lynch syndrome completed questionnaires at three time-points: after receiving a written invitation for a genetic counseling intake (T1), 2-3 days after receiving their DNA test result (T2), and 4-6 weeks later (T3). The psychological impact of the genetic test result was examined shortly and 4-6 weeks after learning their test result. Subsequently, the influence of various potentially prognostic factors on psychological impact were examined in the whole group. Data from 165 counselees were analyzed. Counselees with an unfavorable outcome did not have more emotional distress, but showed significantly more cancer worries 4-6 weeks after learning their test result. Prognostic factors for cancer worries after genetic testing were pre-existing cancer worries, being single, a high risk perception of getting cancer, and an unfavorable test result. Emotional distress was best predicted by pre-existing cancer worries and pre-existing emotional distress. The psychological impact of an unfavorable genetic test result appears considerable if it is measured as "worries about cancer." Genetic counselors should provide additional guidance to counselees with many cancer worries, emotional distress, a high risk perception or a weak social network. PMID:26475052

  19. A consensus prognostic gene expression classifier for ER positive breast cancer

    OpenAIRE

    Teschendorff, Andrew E.; Naderi, Ali; Barbosa-Morais, Nuno L.; Pinder, Sarah E; Ellis, Ian O.; Aparicio, Sam; Brenton, James D.; Caldas, Carlos

    2006-01-01

    Background A consensus prognostic gene expression classifier is still elusive in heterogeneous diseases such as breast cancer. Results Here we perform a combined analysis of three major breast cancer microarray data sets to hone in on a universally valid prognostic molecular classifier in estrogen receptor (ER) positive tumors. Using a recently developed robust measure of prognostic separation, we further validate the prognostic classifier in three external independent cohorts, confirming the...

  20. Syncytin immunoreactivity in colorectal cancer: Potential prognostic impact

    DEFF Research Database (Denmark)

    Larsen, Julie Mou; Christensen, Ib Jarle; Nielsen, Hans Jørgen; Hansen, Ulla; Bjerregaard, Bolette; Talts, Jan Fredrik; Larsson, Lars-Inge

    2009-01-01

    The endogenous retroviral envelope protein syncytin is involved in cell fusions and has also been associated with immunomodulatory functions. Syncytin is currently known to be expressed in the placenta, testis and brain as well as in breast and endometrial carcinomas. Using a newly developed...... monoclonal syncytin antibody we have assessed syncytin expression in a retrospective series of 140 colorectal cancer patients. Variable degrees of syncytin expression were detected in both colonic and rectal tumors and the prognostic impact of such expression was analysed with the Kaplan-Meier method and the...... Cox proportional hazard model. Interestingly, increased syncytin expression was associated with decreased overall survival in rectal but not in colonic cancer patients. Thus, the prognostic impact of syncytin expression appears to vary with the tumor type....

  1. Prognostic impact of CD168 expression in gastric cancer

    International Nuclear Information System (INIS)

    Interactions of stromal hyaluronic acid (HA) with its binding protein RHAMM (receptor for HA-mediated motility) (CD168) have been reported to affect tumor extension and the migration of crucial molecules to promote tumor progression and metastases. Cancerous CD168 expression is correlated with aggressive biological features in several cancers. However, the clinical implications of CD168 positivity in gastric cancer have remained unclear. We examined the CD168 expression of 196 consecutive gastric cancer patients by immunohistochemistry. According to CD168 positivity, the 196 gastric cancer patients were divided into two groups (57 CD168-positive and 139 CD168-negative patients). The correlation between CD168 expression and clinicopathological factors (age, sex, histology, tumor depth, lymph node status, and vessel invasion) was evaluated according to the Japanese Classification of Gastric Carcinoma. Cancerous CD168 expression was detectable in 57 of the 196 tumors (29%). CD168 positivity was significantly correlated with the depth of invasion, nodal involvement, and vessel invasion (p < 0.01). Survival analysis of the 196 gastric cancer patients showed that the CD168-positive group had a significantly higher mortality than the CD168-negative group (p < 0.01). In terms of a correlation with CD168 positivity at separate clinical stages, a significance difference was only found in stages II and III. Multivariate analysis revealed that CD168 expression was a significant independent prognostic marker (p = 0.013) after depth of invasion (p < 0.005) and nodal involvement (p < 0.01). Our results suggest that cancerous CD168 positivity is strongly related to the invasion and metastasis of gastric cancer tumors. These results suggest that cancerous CD168 expression can be used as a prognostic marker of gastric cancer owing to its interactions with stromal hyaluronic acid

  2. Expression and prognostic significance of lysozyme in male breast cancer

    International Nuclear Information System (INIS)

    Lysozyme, one of the major protein components of human milk that is also synthesized by a significant percentage of breast carcinomas, is associated with lesions that have a favorable outcome in female breast cancer. Here we evaluate the expression and prognostic value of lysozyme in male breast cancer (MBC). Lysozyme expression was examined by immunohistochemical methods in a series of 60 MBC tissue sections and in 15 patients with gynecomastia. Staining was quantified using the HSCORE (histological score) system, which considers both the intensity and the percentage of cells staining at each intensity. Prognostic value of lysozyme was retrospectively evaluated by multivariate analysis taking into account conventional prognostic factors. Lysozyme immunostaining was negative in all cases of gynecomastia. A total of 27 of 60 MBC sections (45%) stained positively for this protein, but there were clear differences among them with regard to the intensity and percentage of stained cells. Statistical analysis showed that lysozyme HSCORE values in relation to age, tumor size, nodal status, histological grade, estrogen receptor status, metastasis and histological type did not increase the statistical significance. Univariate analysis confirmed that both nodal involvement and lysozyme values were significant predictors of short-term relapse-free survival. Multivariate analysis, according to Cox's regression model, also showed that nodal status and lysozyme levels were significant independent indicators of short-term relapse-free survival. Tumor expression of lysozyme is associated with lesions that have an unfavorable outcome in male breast cancer. This milk protein may be a new prognostic factor in patients with breast cancer

  3. Zonal Difference and Prognostic Significance of Foxp3 Regulatory T Cell Infiltration in Breast Cancer

    OpenAIRE

    Kim, Sewha; Lee, Anbok; Lim, Woosung; Park, Sanghui; Cho, Min Sun; Koo, Heasoo; Moon, Byung-In; Sung, Sun Hee

    2014-01-01

    Purpose Forkhead box P3 (Foxp3) is known as the most specific marker for regulatory T lymphocytes, which play an important role in immune tolerance to disturb antitumor immunity. The present study aimed to investigate the prognostic significance of Foxp3 regulatory T lymphocyte (Foxp3 Treg) infiltration in breast cancer. Methods Immunohistochemical studies with Foxp3, CD4, and CD8 were performed on representative full tissue sections from 143 patients with invasive ductal carcinoma, not other...

  4. Tissue Biomarkers in Prognostication of Serous Ovarian Cancer following Neoadjuvant Chemotherapy

    OpenAIRE

    Binny Khandakar; Sandeep R Mathur; Lalit Kumar; Sunesh Kumar; Siddhartha Datta Gupta; Venkateswaran K Iyer; Kalaivani, M.

    2014-01-01

    Serous ovarian cancer (SOC) is a significant cause of morbidity and mortality in females with poor prognosis because of advanced stage at presentation. Recently, neoadjuvant chemotherapy (NACT) is being used for management of advanced SOC, but role of tissue biomarkers in prognostication following NACT is not well established. The study was conducted on advanced stage SOC patients (n = 100) that were treated either conventionally (n = 50) or with NACT (n = 50), followed by surgery. In order t...

  5. Prognostics

    Data.gov (United States)

    National Aeronautics and Space Administration — Prognostics has received considerable attention recently as an emerging sub-discipline within SHM. Prognosis is here strictly defined as “predicting the time at...

  6. Predictive and Prognostic Factors in Colorectal Cancer: A Personalized Approach

    Directory of Open Access Journals (Sweden)

    Timothy A. Rockall

    2011-03-01

    Full Text Available It is an exciting time for all those engaged in the treatment of colorectal cancer. The advent of new therapies presents the opportunity for a personalized approach to the patient. This approach considers the complex genetic mechanisms involved in tumorigenesis in addition to classical clinicopathological staging. The potential predictive and prognostic biomarkers which have stemmed from the study of the genetic basis of colorectal cancer and therapeutics are discussed with a focus on mismatch repair status, KRAS, BRAF, 18qLOH, CIMP and TGF-β.

  7. Gender differences in prognostic factors for oral cancer.

    Science.gov (United States)

    Honorato, J; Rebelo, M S; Dias, F L; Camisasca, D R; Faria, P A; Azevedo e Silva, G; Lourenço, S Q C

    2015-10-01

    The aim of this study was to assess gender differences in prognostic factors among patients treated surgically for oral squamous cell carcinoma (OSCC). The medical records of 477 eligible patients (345 males, 132 females) obtained from the Brazilian Cancer Institute were reviewed. Survival was calculated by Kaplan-Meier method. Cox regression models were used to obtain adjusted hazard ratios (aHR) for males and females. Multivariate analysis showed that past tobacco use (aHR 0.2, 95% confidence interval (CI) 0.1-0.7) and regional metastasis (aHR 2.3, 95% CI 1.5-3.5) in males, and regional metastasis (aHR 2.2, 95% CI 1.2-4.3), distant metastasis (aHR 6.7, 95% CI 1.3-32.7), and hard palate tumours (aHR 11.8, 95% CI 3.3-47.7) in females, were associated with a higher risk of death. There were no differences in survival between males and females. Regional metastasis was found to be a negative prognostic factor in OSCC for both genders. Past tobacco use was an independent prognostic factor for worse survival among males, while distant metastasis and hard palate tumours were independent prognostic factors for worse survival among females. Further studies are necessary to corroborate the relationships found in this study. PMID:26183881

  8. Clinical and prognostic significance of plasma fibrinogen in lung cancer

    Directory of Open Access Journals (Sweden)

    Chen YS

    2014-01-01

    Full Text Available Objectives: Hyperfibrinogenemia is a common problem associated with various carcinomas. The recent studies have shown that high plasma fibrinogen concentration is associated with invasion, growth and metastases of cancer. Furthermore, the recent studies focus on the prognostic significance of fibrinogen in the patients with advanced NSCLC (stage IIIB -IV. However, the prognostic significance of the plasma fibrinogen levels in early stage NSCLC patients (stage I -IIIA still remains unclear. In addition, it remains unclear whether or not chemotherapy-induced changes in fibrinogen level relate to the prognosis. The aims of this study were to 1 further explore the relationship between the plasma fibrinogen concentration and the stage and metastases of lung cancer 2 evaluate the prognostic significance of the basal plasma fibrinogen level in patients with lung cancer 3 explore the prognostic value of the change in fibrinogen levels between pre and post-chemotherapy. Methods: In this retrospective study, the data from 370 patients with lung cancer were enrolled into this study. The plasma fibrinogen levels were compared with the clinical and prognostic significance of lung cancer. The association between the plasma fibrinogen level and clinical-prognostic characteristics were analyzed using SPSS 17.0 software. Results: 1 The median pre-treatment plasma fibrinogen levels were 4.20g/L. Pre-treatment plasma fibrinogen levels correlated significantly with gender (p = 0.013. A higher plasma fibrinogen concentration was associated with squamous cell carcinoma versus adenocarcinoma (4.83±1.50 g/L versus 4.15±1.30 g/L; P<0.001, there was a significant association between plasma fibrinogen level and metastases of lung cancer, pointing a higher plasma fibrinogen level in lymph nodes or distant organ metastases (p < 0.001. 2 Patients with low plasma fibrinogen concentration demonstrates higher overall survival compared with those with high plasma fibrinogen

  9. Patient-specific data fusion defines prognostic cancer subtypes.

    Directory of Open Access Journals (Sweden)

    Yinyin Yuan

    2011-10-01

    Full Text Available Different data types can offer complementary perspectives on the same biological phenomenon. In cancer studies, for example, data on copy number alterations indicate losses and amplifications of genomic regions in tumours, while transcriptomic data point to the impact of genomic and environmental events on the internal wiring of the cell. Fusing different data provides a more comprehensive model of the cancer cell than that offered by any single type. However, biological signals in different patients exhibit diverse degrees of concordance due to cancer heterogeneity and inherent noise in the measurements. This is a particularly important issue in cancer subtype discovery, where personalised strategies to guide therapy are of vital importance. We present a nonparametric Bayesian model for discovering prognostic cancer subtypes by integrating gene expression and copy number variation data. Our model is constructed from a hierarchy of Dirichlet Processes and addresses three key challenges in data fusion: (i To separate concordant from discordant signals, (ii to select informative features, (iii to estimate the number of disease subtypes. Concordance of signals is assessed individually for each patient, giving us an additional level of insight into the underlying disease structure. We exemplify the power of our model in prostate cancer and breast cancer and show that it outperforms competing methods. In the prostate cancer data, we identify an entirely new subtype with extremely poor survival outcome and show how other analyses fail to detect it. In the breast cancer data, we find subtypes with superior prognostic value by using the concordant results. These discoveries were crucially dependent on our model's ability to distinguish concordant and discordant signals within each patient sample, and would otherwise have been missed. We therefore demonstrate the importance of taking a patient-specific approach, using highly-flexible nonparametric

  10. Prognostic value of PLR in various cancers: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Xin Zhou

    Full Text Available BACKGROUND: Recently, more and more studies investigated the association of inflammation parameters such as the Platelet Lymphocyte Ratio (PLR and the prognosis of various cancers. However, the prognostic role of PLR in cancer remains controversial. METHODS: We conducted a meta-analysis of published studies to evaluate the prognostic value of PLR in various cancers. In order to investigate the association between PLR and overall survival (OS, the hazard ratio (HR and its 95% confidence interval (CI were calculated. RESULTS: A total of 13,964 patients from 26 studies were included in the analysis. The summary results showed that elevated PLR was a negative predictor for OS with HR of 1.60 (95%CI: 1.35-1.90; Pheterogeneity <0.001. Subgroup analysis revealed that increased PLR was a negative prognostic marker in patients with gastric cancer (HR = 1.35, 95%CI: 0.80-2.25, Pheterogeneity = 0.011, colorectal cancer (HR = 1.65, 95%CI: 1.33-2.05, Pheterogeneity = 0.995, hepatocellular carcinoma (HR = 3.07, 95% CI: 2.04-4.62, Pheterogeneity = 0.133, ovarian cancer (HR = 1.57, 95%CI: 1.07-2.31, Pheterogeneity = 0.641 and non-small cell lung cancer (NSCLC (HR = 1.85, 95% CI: 1.42-2.41, Pheterogeneity = 0.451 except for pancreatic cancer (HR = 1.00, 95%CI: 0.92-1.09, Pheterogeneity = 0.388. CONCLUSION: The meta-analysis demonstrated that PLR could act as a significant biomarker in the prognosis of various cancers.

  11. Immunoexpression analysis and prognostic value of BLCAP in breast cancer

    DEFF Research Database (Denmark)

    Gromova, Irina; Gromov, Pavel; Kroman, Niels;

    2012-01-01

    62-patient sample matched cohort, that immunostaining intensity for BLCAP was increased in tumors relative to normal tissue, in more than 45% of the cases examined, indicating that BLCAP may be of value as a marker for breast cancer. We also analyzed BLCAP expression and prognostic value using a set...... as cervical and renal cancer, as well as human tongue carcinoma and osteosarcoma. Here we report the first study of the expression patterns of BLCAP in breast tissue. We analyzed by immunohistochemistry tissue sections of normal and malignant specimens collected from 123 clinical high-risk breast...... cancer patients within the Danish Center for Translational Breast Cancer Research (DCTB) prospective study dataset. The staining pattern, the distribution of the immunostaining, and its intensity were studied in detail. We observed weak immunoreactivity for BLCAP in mammary epithelial cells, almost...

  12. Depression as a prognostic factor for breast cancer mortality

    DEFF Research Database (Denmark)

    Hjerl, Karen; Andersen, Elisabeth W; Keiding, Niels;

    2003-01-01

    affective and anxiety disorders were divided and categorized into five ordinal diagnostic groups. Early-stage (N=10382) and late-stage (N=10211) breast cancer patients were analyzed separately with Cox's regression adjusted for well-documented somatic prognostic variables. The authors used survival analysis......It is unclear if depression or depressive symptoms have an effect on mortality in breast cancer patients. In this population-based, nationwide, retrospective cohort study in Denmark, depression was defined as affective or anxiety disorders that necessitated psychiatric hospital admission. All the...... of data from three central registers and found that breast cancer patients with depression had a modestly but significantly higher risk of mortality depending on stage of breast cancer and time of depression. The same result was found after censoring unnatural causes of death such as accident...

  13. Short-Term Prognostic Index for Breast Cancer: NPI or Lpi

    OpenAIRE

    Van Belle, V.; Decock, J; Hendrickx, W.; Brouckaert, O.; Pintens, S.; Moerman, P; Wildiers, H; Paridaens, R.; M. R. Christiaens; Van Huffel, S.; Neven, P.

    2011-01-01

    Axillary lymph node involvement is an important prognostic factor for breast cancer survival but is confounded by the number of nodes examined. We compare the performance of the log odds prognostic index (Lpi), using a ratio of the positive versus negative lymph nodes, with the Nottingham Prognostic Index (NPI) for short-term breast cancer specific disease free survival. A total of 1818 operable breast cancer patients treated in the University Hospital of Leuven between 2000 and 2005 were ...

  14. Prognostic factors in 165 elderly colorectal cancer patients

    Institute of Scientific and Technical Information of China (English)

    Ke-Jun Nan; Hai-Xia Qin; Guang Yang

    2003-01-01

    AIM: To analyse the prognostic factors in 165 colorectal patients aged ≥70.METHODS: One hundred and sixty-five elderly patients with colorectal cancer diagnosed by histology were entered into the retrospective study between 1994 and 2001. Patients were given optimal operation alone, chemotherapy after operation, or chemotherapy alone according to tumor stage,histology, physical strength, and co-morbid problems.Survival rate was calculated by Kaplan-Meier method, and compared with meaningful variances by Log-rank method.Prognostic factors were analyzed by Cox regression.RESULTS: The 1,2,3,4,5 year survival rate (all-cause rnortality)was 87.76%, 65.96%, 52.05%, 42.77%, 40.51%,respectively. The mean survival time was 41.89±2.33 months (95% CI: 37.33-46.45 months), and the median survival time was 37 months. Univariate analysis showed that factors such as age, nodal metastasis, treatment method, Duke's stage, gross findings, kind of histology, and degree of differentiation had influences on the survival rate. Multivariate analysis showed that factors such as treatment method,Duke's stage, kind of histology and degree of differentiation were independent prognostic factors.CONCLUSION: This study suggests that the prognosis of elderly colorectal cancer patients is influenced by several factors. Most of elderly patients can endure surgery and/or chemotherapy, and have a long-time survival and good quality of life.

  15. Prognostic Role of microRNA-155 in Various Carcinomas: Results from a Meta-Analysis

    OpenAIRE

    Jing He; Fengmei Zhang; Ying Wu; Xiaoli Zhu; Xuelian He; Yuhang Zhao; , Wei Zhang; Yulan Zhao

    2013-01-01

    BACKGROUND: Recent studies have shown that microRNAs (miRNA) have prognostic values in cancers. This meta-analysis seeks to summarize the global predicting role of miR-155 for survival in patients with a variety of carcinomas. METHODS: Eligible studies were identified through multiple search strategies. Data were extracted from studies investigating the relationship between miR-155 expression and survival in cancer patients. Combined hazard ratios (HRs) of miR-155 for outcome were analyzed. R...

  16. Radiation therapy of the nasopharyngeal cancer and its prognostic factors

    International Nuclear Information System (INIS)

    39 patients with the regional nasopharyngeal cancer (NPC) underwent radiation therapy from 1975 through 1984 in the Department of Radiology, Chiba University Hospital. A retrospective study was carried out to find out prognostic factors of the NPC patients. Radiation therapy was performed under megavoltage condition. 31 patients were given more than 50 Gy. 41% of the whole had T4 extension and 69% had lymph node metastasis. The pathological slides were reviewed and classified by the proposal of Shanmugaratnam. Advanced N-stage and the absence of the lymphocytic infiltration tended to affect the survival unfavorably, whereas the prognostic significance of histology, especially of keratinizing squamous cell carcinoma remained unclear. T4 lesion often recurred even with high dose radiation therapy. To improve the local control rate in NPC, wide field irradiation from the base of skull to the lower neck seemed necessary as well as the dosage greater than 66 Gy. (orig.)

  17. Methylator phenotype in colorectal cancer: A prognostic factor or not?

    Science.gov (United States)

    Gallois, C; Laurent-Puig, P; Taieb, J

    2016-03-01

    Colorectal cancer (CRC) is due to different types of genetic alterations that are translated into different phenotypes. Among them, CpG island methylator phenotype (CIMP+) is the most recently involved in carcinogenesis of some CRC. The malignant transformation in this case is mainly due to the transcriptional inactivation of tumor suppressor genes. CIMP+ are reported to be more frequently found in the elderly and in women. The tumors are more frequently located in the proximal part of the colon, BRAF mutated and are associated with microsatellite instability (MSI) phenotype. All sporadic MSI CRC belong to the methylator phenotype, however some non MSI CRC may also harbor a methylator phenotype. The prognostic value of CIMP is not well known. Most studies show a worse prognosis in CIMP+ CRC, and adjuvant treatments seem to be more efficient. We review here the current knowledge on prognostic and predictive values in CIMP+ CRC. PMID:26702883

  18. Evaluation of miR-21 and miR-375 as prognostic biomarkers in esophageal cancer

    DEFF Research Database (Denmark)

    Winther, Mette; Alsner, Jan; Tramm, Trine;

    2015-01-01

    BACKGROUND: MicroRNAs (miRNAs) have been associated with prognosis in esophageal cancer, suggesting a role for miRNAs to help guide treatment decisions. Especially, miR-21 and miR-375 have been investigated as prognostic biomarkers. The aim of this study was to evaluate the prognostic potential of...... miR-21 and miR-375 in primary esophageal squamous cell carcinomas (ESCC) and esophagogastric adenocarcinomas (EAC). MATERIAL AND METHODS: Pre-therapeutic tumor specimens from 195 patients with loco-regional esophageal cancer treated with neoadjuvant or definitive chemoradiotherapy or perioperative...

  19. DIAGNOSTIC AND PROGNOSTIC UTILITY OF SERUM PSA IN BREAST CANCER

    Institute of Scientific and Technical Information of China (English)

    张淑群; 强水云; 李妙羡; 纪宗正

    2004-01-01

    Objective To investigate the diagnostic and prognostic value of total and free prostate-specific antigen (PSA) in breast cancer women. Methods Using the microparticle enzyme immunoassay system, we measured the concentrations of these markers in the sera of 85 women with breast cancer and in 30 healthy women.Results Free PSA levels were significantly higher in women with breast cancer than healthy women (P <0. 05 ).The percentage of free PSA predominant subjects was 37. 6% in breast cancer patients and 3. 3% in healthy women.In women with breast cancer,total PSA positivity was 23.5% and free PSA positivity was 27. 1%. When compared to negatives,total PSA positive patients had a higher percentage of lymph node involvement tamours ( P >0. 05).However, patients with predominant free PSA had a higher percentage of early stage than patients with predominant PSA-ACT. Conclusion This study indicate clinical significance of preoperative measurement of serum total and free PSA in diagnosis and prognosis of women with breast cancer. The expression of KLKs is correlated with carcinogenesis of breast cancer.

  20. Prognostic Value of Homotypic Cell Internalization by Nonprofessional Phagocytic Cancer Cells

    Directory of Open Access Journals (Sweden)

    Manuela Schwegler

    2015-01-01

    Full Text Available Background. In this study, we investigated the prognostic role of homotypic tumor cell cannibalism in different cancer types. Methods. The phenomenon of one cell being internalized into another, which we refer to as “cell-in-cell event,” was assessed in 416 cases from five head and neck cancer cohorts, as well as one anal and one rectal cancer cohort. The samples were processed into tissue microarrays and immunohistochemically stained for E-cadherin and cleaved caspase-3 to visualize cell membranes and apoptotic cell death. Results. Cell-in-cell events were found in all of the cohorts. The frequency ranged from 0.7 to 17.3 cell-in-cell events per mm2. Hardly any apoptotic cells were found within the cell-in-cell structures, although apoptotic cell rates were about 1.6 to two times as high as cell-in-cell rates of the same tissue sample. High numbers of cell-in-cell events showed adverse effects on patients’ survival in the head and neck and in the rectal cancer cohorts. In multivariate analysis, high frequency was an adverse prognostic factor for overall survival in patients with head and neck cancer (p=0.008. Conclusion. Cell-in-cell events were found to predict patient outcomes in various types of cancer better than apoptosis and proliferation and might therefore be used to guide treatment strategies.

  1. The prognostic impact of epidermal growth factor receptor in patients with metastatic gastric cancer

    Directory of Open Access Journals (Sweden)

    Atmaca Akin

    2012-11-01

    Full Text Available Abstract Background The epidermal growth factor receptor (EGFR is a potential target of anticancer therapy in gastric cancer. However, its prognostic role in metastatic gastric or gastroesophageal junction (GE cancer has not been established yet. Methods EGFR status was analyzed by immunohistochemistry (IHC in paraffin-embedded samples from 357 patients who received chemotherapy in 4 first-line trials. Automated RNA extraction from paraffin and RT-quantitative PCR were additionally used to evaluate EGFR mRNA expression in 130 patients. Results EGFR protein expression (any grade and overexpression (3+ were observed in 43% and 11% of patients, respectively. EGFR positivity correlated with intestinal type histology (p = 0.05, but not with other clinicopathologic characteristics. Median follow-up was 18.2 months. Median overall survival (OS was similar in patients with EGFR positive vs. those with EGFR negative tumors, regardless whether positivity was defined as ≥1+ (10.6 vs. 10.9 months, p = 0.463 or as 3+ (8.6 vs. 10.8 months, p = 0.377. The multivariate analysis indicated that EGFR status is not an independent prognostic factor (hazard ratio 0.85, 0.56 to 1.12, p = 0.247. There were also no significant differences in overall survival when patients were categorized according to median (p = 0.116 or quartile (p = 0.767 distribution of EGFR mRNA gene expression. Similar distributions of progression-free survival according to EGFR status were observed. Conclusions Unlike different cancer types where EGFR-positive disease is associated with an adverse prognostic value, EGFR positivity is not prognostic of patient outcome in metastatic gastric or GE cancer.

  2. Inflammation-based prognostic scores and nutritional prognostic index in patients with locally-advanced unresectable colorectal cancer

    OpenAIRE

    Ikeguchi, Masahide; Urushibara, Sho-ichi; Shimoda, Ryugo; Yamamoto, Manabu; MAETA, YOSHIHIKO; Ashida, Keigo

    2014-01-01

    Background Unresectable colorectal cancer has a poor prognosis. However, some patients survive intensive chemotherapy, and complete resection of primary and metastatic tumors may even be possible. In the present study, we examined the prognostic factors associated with survival after intensive chemotherapy in patients with unresectable colorectal cancer. Methods This retrospective study enrolled 61 patients diagnosed with unresectable locally advanced colorectal cancer between January 2004 an...

  3. Nuclear PARP1 expression and its prognostic significance in breast cancer patients.

    Science.gov (United States)

    Mazzotta, Annalisa; Partipilo, Giulia; De Summa, Simona; Giotta, Francesco; Simone, Giovanni; Mangia, Anita

    2016-05-01

    Poly(adenosine diphosphate [ADP]-ribose) polymerase 1 (PARP1) plays important roles in DNA damage response pathways and is often overexpressed in various human tumors. Currently, the use of PARP inhibitors for breast cancer (BC) therapy is the subject of debate, and there is an urgent need to understand much the expression and prognostic role of the PARP1 protein. The aim was to investigate the clinicopathological and prognostic significance of PARP1 in BC patients. The PARP1 and breast cancer susceptibility gene 1 (BRCA1) protein expressions were evaluated in 114 BCs by immunohistochemistry. Disease-free survival (DFS) and overall survival (OS) were determined based on the Kaplan-Meier method. Our results showed that nuclear PARP1 expression was significantly associated with peritumoral vascular invasion (P = 0.046), chemotherapeutic treatment (P = 0.026), oestrogen receptor (ER; P = 0.013), human epidermal growth factor receptor 2 (HER2; P = 0.003) and BRCA1 (P PARP1 expression was associated with decreased DFS (P = 0.012) and OS (P = 0.026). In conclusion, PARP1 expression may be used as an independent prognostic factor in BC patients. In addition, this study demonstrated that high PARP1 expression may represent a marker of poorer prognosis both for patients with worse clinical outcome and in less aggressive clinical conditions. PMID:26614429

  4. Prognostic value of mitotic index and Bcl2 expression in male breast cancer.

    OpenAIRE

    Lacle, M.M.; van der Pol, C.C.; Witkamp, A. J.; van der Wall, E.; van Diest, P.J.

    2013-01-01

    The incidence of male breast cancer (MBC) is rising. Current treatment regimens for MBC are extrapolated from female breast cancer (FBC), based on the assumption that FBC prognostic features and therapeutic targets can be extrapolated to MBC. However, there is yet little evidence that prognostic features that have been developed and established in FBC are applicable to MBC as well. In a recent study on FBC, a combination of mitotic index and Bcl2 expression proved to be of strong prognostic v...

  5. Preoperative CYFRA 21-1 level as a prognostic indicator in resected primary squamous cell lung cancer.

    OpenAIRE

    Niklinski, J.; Furman, M; Burzykowski, T.; Chyczewski, L.; Laudanski, J.; Chyczewska, E; Rapellino, M.

    1996-01-01

    The CYFRA 21-1 assay is a test that has been developed recently for detection of a cytokeratin 19 fragment in serum. A diagnostic role for CYFRA 21-1 has already been proposed. The question of whether this marker is prognostically significant is important in clarifying the role of CYFRA 21-1 in clinical practice. The aim of this study was to evaluate the prognostic significance of elevated preoperative CYFRA 21-1 levels in patients with resected primary squamous-cell lung cancer (SqCC). Serum...

  6. Prognostic Significance of Immunoreactive Neutrophil Elastase in Human Breast Cancer: Long-Term Follow-Up Results in 313 Patients

    Directory of Open Access Journals (Sweden)

    Miwa Akizuki

    2007-03-01

    Full Text Available OBJECTIVE: We have measured the concentration of immunoreactive neutrophil elastase (ir-NE in the tumor extracts of 313 primary human breast cancers. Sufficient time has elapsed, and we are now ready to analyze its prognostic value in human breast cancer. METHODS: ir-NE concentration in tumor extracts was determined with an enzyme-linked immunosorbent assay that enables a rapid measurement of both free-form ir-NE and the α1-protease inhibitor-complexed form of ir-NE. We analyzed the prognostic value of this enzyme in human breast cancer in univariate and multivariate analyses. RESULTS: Patients with breast cancer tissue containing a high concentration of ir-NE had poor survival compared to those with a low concentration of ir-NE at the cutoff point of 9.0 µg/100 mg protein (P = .0012, which had been previously determined in another group of 49 patients. Multivariate stepwise analysis selected lymph node status (P= .0004; relative risk = 1.46 and ir-NE concentration (P= .0013; relative risk = 1.43 as independent prognostic factors for recurrence. CONCLUSIONS: Tumor ir-NE concentration is an independent prognostic factor in patients with breast cancer who undergo curative surgery. This enzyme may play an active role in tumor progression that leads to metastasis in human breast cancer.

  7. Cancer of the glottis: prognostic factors in radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Mantravadi, R.V.; Liebner, E.J.; Haas, R.E.; Skolnik, E.M.; Applebaum, E.L.

    1983-10-01

    The authors conducted a multivariate analysis of the prognostic factors in 96 patients with early glottic cancer treated by radiation therapy. Of these, 73 had T1 and 23 had T2 tumor. The primary tumor was controlled in 82% of T1 and 74% of T2 lesions. Actuarial five-year survival rates were 87% for T1 and 74% for T2. Carcinoma of the anterior commissure associated with bilateral vocal cord involvement, subglottic tumor extension, persistent or recurrent laryngeal edema, and impaired cord mobility was found to adversely influence the prognosis. The data suggest that irradiation is the treatment of choice for glottic cancer limited to the vocal cords or with minimal extension to the anterior commissure or supraglottic larynx.

  8. Cancer of the glottis: prognostic factors in radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Mantravadi, R.V.P.; Liebner, E.J.; Haas, R.E.; Skolnik, E.M.; Applebaum, E.L.

    1983-10-01

    The authors conducted a multivariate analysis of the prognostic factors in 96 patients with early glottic cancer treated by radiation therapy. Of these, 73 had T/sub 1/ and 23 had T/sub 2/ tumor. The primary tumor was controlled in 82% of T/sub 1/ amd 74% for T/sub 2/. Carcinoma of the anterior commissure associated with bilateral vocal cord involvement, subglottic tumor extension, persistent or recurrent laryngeal edema, and impaired cord mobility was found to adversely influence the prognosis. The data suggest that irradiation is the treatment of choice for glottic cancer limited to the vocal cords or with minimal extension to the anterior commissure or gupraglottic larynx.

  9. MUC1 Immunohistochemical Expression as a Prognostic Factor in Gastric Cancer: Meta-Analysis

    Science.gov (United States)

    Wang, Xiao-Tong; Kong, Fan-Biao; Mai, Wei; Li, Lei; Pang, Li-Ming

    2016-01-01

    MUC1, a member of the mucin family, is expressed in tumors of various human organs and may function as an antiadhesion molecule that inhibits cell-to-cell adhesion, inducing tumor metastasis, and served as a potential biomarker of tumor progression in early gastric cancer. However, its prognostic significance in gastric cancer is still in dispute. We performed a meta-analysis to evaluate the relationship between MUC1 expression and prognosis of gastric cancer. A total of ten eligible studies with 834 cases and 548 controls were included. MUC1 positive cases were highly positive in intestinal-type carcinomas (OR = 1.76, 95% CI: 1.27–2.44, P = 0.0008 fixed-effect), higher rate of vascular invasion (OR = 1.64, 95% CI: 1.13–2.39, P = 0.009 fixed-effect), and lymph node metastasis (OR = 2.10, 95% CI: 1.20–3.67, P = 0.01 random-effect), as well as lower 5-year survival rate (HR = 0.27, 95% CI: 0.11–0.66, P = 0.004 random-effect). However, the presence of MUC1 was not associated with gender, tumor size, histologic differentiation, and clinical stage. In summary, MUC1 is a prognostic factor in gastric cancer, which acts as a marker of poor outcome in patients with gastric cancer. Further clinical studies are needed to confirm the role of MUC1 in clinical practice.

  10. Immunohistochemical detection of HIF-1α and CAIX in advanced head-and-neck cancer. Prognostic role and correlation with tumor markers and tumor oxygenation parameters

    International Nuclear Information System (INIS)

    Background: tumor hypoxia has an impact on the outcome of cancer patients treated with radiotherapy. The validity of endogenous markers such as hypoxia-inducible factor-1α (HIF-1α) and carbonic anhydrase isozyme IX (CAIX) to detect therapeutically relevant levels of hypoxia within tumors is controversially discussed. Furthermore, the association of these hypoxia markers with tumor markers or tumor oxygenation parameters is of importance for understanding the relationship between the different factors. Patients and methods: tumor tissue sections of 34 patients with advanced head-and-neck cancer treated with radio(chemo)therapy were assessed by immunohistochemistry for the expression of HIF-1α and CAIX. The relationships of both markers with tumor oxygenation parameters, molecular factors like P53, OPN, VEGF, VHL, survivin, and Ki67 levels, and clinical parameters were studied. Results: bivariate analysis showed a significant correlation of HIF-1α expression with high P53 and high OPN expression, high serum VEGF levels, and low VHL and low Ki67 expression. The CAIX expression was inversely correlated with pH value and directly correlated with T-stage. However, no correlation was found between HIF-1α and CAIX expression. Neither in a univariate Cox proportional hazard regression nor in a Kaplan-Meier analysis did expression of HIF-1α or CAIX have a significant impact on clinical outcome. However, in a Kaplan-Meier analysis, the combination of both factors showed that patients with intratumoral overexpression of either HIF-1α or CAIX or both markers died on average 2 years earlier than patients whose tumors had low expression of both factors (p < 0.05). Conclusion: expression of HIF-1α and CAIX was correlated with different tumor parameters. Only combined HIF-1α and CAIX expression was significantly predictive of patients' overall survival. (orig.)

  11. Elovl6 is a poor prognostic predictor in breast cancer

    Science.gov (United States)

    FENG, YIN-HSUN; CHEN, WEI-YU; KUO, YU-HSUAN; TUNG, CHAO-LING; TSAO, CHAO-JUNG; SHIAU, AI-LI; WU, CHAO-LIANG

    2016-01-01

    Elongation of long chain fatty acids family member 6 (Elovl6) has been demonstrated to be involved in insulin resistance, obesity and lipogenesis. In addition, it has been reported that the protein is upregulated in human hepatocellular carcinoma and is implicated in nonalcoholic steatohepatitis-associated liver carcinogenesis. Excess body weight has been associated with an increased risk of postmenopausal breast cancer and poor prognosis. However, the connection between Elovl6 expression and outcome of breast cancer remains uncertain. Therefore, the present study used immunohistochemical analysis to investigate the expression of Elovl6 in breast cancer tissues from patients who had undergone curative mastectomy. Out of a total of 70 patients, 37.1% of patients exhibited positive Elovl6 expression in breast cancer tissue, whilst 62.9% were considered as negative. Positive Elov16 expression correlated with positive lymph node involvement and shorter recurrence-free survival. However, Elovl6 expression had no association with primary tumor size, lymph node metastasis, stage, grade, estrogen receptor, progesterone receptor, HER2 and age. Therefore, positive Elovl6 expression is a poor prognostic factor in patients with breast cancer that have previously undergone surgery, and may function as a potential therapeutic approach in the future, particularly in the scope of obesity related disease. PMID:27347126

  12. The role of HER family signalling in breast cancer

    OpenAIRE

    Kuruppu, Anchala

    2016-01-01

    The HER family of receptors plays a major role in a variety of cancers including breast cancer. Several researchers have shown that HER family overexpression in breast cancer is a significant prognostic factor, especially for survival and relapse. Therefore, many therapeutics are being developed to test the impact of HER family blockade in breast cancer. Although numerous therapies have been developed, many have not been very successful in the clinic. This is often a consequence of cancer cel...

  13. Activated leukocyte cell adhesion molecule in breast cancer: prognostic indicator

    International Nuclear Information System (INIS)

    Activated leukocyte cell adhesion molecule (ALCAM) (CD166) is an immunoglobulin molecule that has been implicated in cell migration. The present study examined the expression of ALCAM in human breast cancer and assessed its prognostic value. The immunohistochemical distribution and location of ALCAM was assessed in normal breast tissue and carcinoma. The levels of ALCAM transcripts in frozen tissue (normal breast, n = 32; breast cancer, n = 120) were determined using real-time quantitative PCR. The results were then analyzed in relation to clinical data including the tumor type, the grade, the nodal involvement, distant metastases, the tumor, node, metastasis (TNM) stage, the Nottingham Prognostic Index (NPI), and survival over a 6-year follow-up period. Immunohistochemical staining on tissue sections in ducts/acini in normal breast and in breast carcinoma was ALCAM-positive. Differences in the number of ALCAM transcripts were found in different types of breast cancer. The level of ALCAM transcripts was lower (P = 0.05) in tumors from patients who had metastases to regional lymph nodes compared with those patients without, in higher grade tumors compared with Grade 1 tumors (P < 0.01), and in TNM Stage 3 tumors compared with TNM Stage 1 tumors (P < 0.01). Tumors from patients with poor prognosis (with NPI > 5.4) had significantly lower levels (P = 0.014) of ALCAM transcripts compared with patients with good prognosis (with NPI < 3.4), and tumors from patients with local recurrence had significantly lower levels than those patients without local recurrence or metastases (P = 0.04). Notably, tumors from patients who died of breast cancer had significantly lower levels of ALCAM transcripts (P = 0.0041) than those with primary tumors but no metastatic disease or local recurrence. Patients with low levels of ALCAM transcripts had significantly (P = 0.009) more incidents (metastasis, recurrence, death) compared with patients with primary breast tumors with high levels of

  14. Cathepsin b: a potential prognostic marker for inflammatory breast cancer

    OpenAIRE

    Cavallo-Medved Dora; Shaalan Mohamed A; El-Shinawi Mohamed; Mohamed Mona M; Nouh Mohamed A; Khaled Hussein M; Sloane Bonnie F

    2011-01-01

    Abstract Background Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer. In non-IBC, the cysteine protease cathepsin B (CTSB) is known to be involved in cancer progression and invasion; however, very little is known about its role in IBC. Methods In this study, we enrolled 23 IBC and 27 non-IBC patients. All patient tissues used for analysis were from untreated patients. Using immunohistochemistry and immunoblotting, we assessed the levels of expression of CTSB in IB...

  15. Hedgehog pathway aberrations and gastric cancer; evaluation of prognostic impact and exploration of therapeutic potentials.

    Science.gov (United States)

    Abdel-Rahman, Omar

    2015-03-01

    Gastric cancer is an important cause for mortality and morbidity worldwide; it lies in the fourt rank as a cause of cancer-related death in males and in the fifth rank of cancer-related death in women. The prognosis of advanced/metastatic gastric cancer cases looks poor with the majority of available therapeutics. Thus, novel therapeutic strategies in this setting have been considered a priority for leading cooperative oncology groups. Hedgehog(Hh) pathway aberrations have sparked particular interest as prognostic markers with data from multiple studies showing consistent evidence of a poor prognostic value of Gli over expression in gastric cancer while on the other hand the prognostic significance of Hh protein over expression (particularly SHH) was not consistent among different studies. This review article revises the prognostic and potential therapeutic opportunities in the targeting of hedgehog pathway in gastric cancer. PMID:25680409

  16. Meta-analysis confirms BCL2 is an independent prognostic marker in breast cancer

    International Nuclear Information System (INIS)

    A number of protein markers have been investigated as prognostic adjuncts in breast cancer but their translation into clinical practice has been impeded by a lack of appropriate validation. Recently, we showed that BCL2 protein expression had prognostic power independent of current used standards. Here, we present the results of a meta-analysis of the association between BCL2 expression and both disease free survival (DFS) and overall survival (OS) in female breast cancer. Reports published in 1994–2006 were selected for the meta-analysis using a search of PubMed. Studies that investigated the role of BCL2 expression by immunohistochemistry with a sample size greater than 100 were included. Seventeen papers reported the results of 18 different series including 5,892 cases with an average median follow-up of 92.1 months. Eight studies investigated DFS unadjusted for other variables in 2,285 cases. The relative hazard estimates ranged from 0.85 – 3.03 with a combined random effects estimate of 1.66 (95%CI 1.25 – 2.22). The effect of BCL2 on DFS adjusted for other prognostic factors was reported in 11 studies and the pooled random effects hazard ratio estimate was 1.58 (95%CI 1.29–1.94). OS was investigated unadjusted for other variables in eight studies incorporating 3,910 cases. The hazard estimates ranged from 0.99–4.31 with a pooled estimate of risk of 1.64 (95%CI 1.36–2.0). OS adjusted for other parameters was evaluated in nine series comprising 3,624 cases and the estimates for these studies ranged from 1.10 to 2.49 with a pooled estimate of 1.37 (95%CI 1.19–1.58). The meta-analysis strongly supports the prognostic role of BCL2 as assessed by immunohistochemistry in breast cancer and shows that this effect is independent of lymph node status, tumour size and tumour grade as well as a range of other biological variables on multi-variate analysis. Large prospective studies are now needed to establish the clinical utility of BCL2 as an independent

  17. Meta-analysis confirms BCL2 is an independent prognostic marker in breast cancer

    Directory of Open Access Journals (Sweden)

    Pharoah Paul DP

    2008-05-01

    Full Text Available Abstract Background A number of protein markers have been investigated as prognostic adjuncts in breast cancer but their translation into clinical practice has been impeded by a lack of appropriate validation. Recently, we showed that BCL2 protein expression had prognostic power independent of current used standards. Here, we present the results of a meta-analysis of the association between BCL2 expression and both disease free survival (DFS and overall survival (OS in female breast cancer. Methods Reports published in 1994–2006 were selected for the meta-analysis using a search of PubMed. Studies that investigated the role of BCL2 expression by immunohistochemistry with a sample size greater than 100 were included. Seventeen papers reported the results of 18 different series including 5,892 cases with an average median follow-up of 92.1 months. Results Eight studies investigated DFS unadjusted for other variables in 2,285 cases. The relative hazard estimates ranged from 0.85 – 3.03 with a combined random effects estimate of 1.66 (95%CI 1.25 – 2.22. The effect of BCL2 on DFS adjusted for other prognostic factors was reported in 11 studies and the pooled random effects hazard ratio estimate was 1.58 (95%CI 1.29–1.94. OS was investigated unadjusted for other variables in eight studies incorporating 3,910 cases. The hazard estimates ranged from 0.99–4.31 with a pooled estimate of risk of 1.64 (95%CI 1.36–2.0. OS adjusted for other parameters was evaluated in nine series comprising 3,624 cases and the estimates for these studies ranged from 1.10 to 2.49 with a pooled estimate of 1.37 (95%CI 1.19–1.58. Conclusion The meta-analysis strongly supports the prognostic role of BCL2 as assessed by immunohistochemistry in breast cancer and shows that this effect is independent of lymph node status, tumour size and tumour grade as well as a range of other biological variables on multi-variate analysis. Large prospective studies are now needed to

  18. Is Absolute Lymphocyte Count Just Another Prognostic Factor in Cancer?

    OpenAIRE

    Porrata, Luis F.; Markovic, Svetomir N.

    2010-01-01

    The role of host immunity in cancer clinical outcomes has been wellestablished in animal models. In humans, the impact of the immune system as a therapeutic maneuver to treat malignancies has been proven by the development of graft-versus-tumor effect observed in the allogeneic stem cell transplantation. However, with few notable exceptions, no definitive conclusions have been reached as to the role of host immunity in humans and its impact on cancer outcomes. This article reviews the clinica...

  19. Prognostic significance of S100A4 and vascular endothelial growth factor expression in pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Kai-Xing Ai; Lin-Yuan Lu; Xin-Yu Huang; Wei Chen; Hui-Zhen Zhang

    2008-01-01

    AIM:To investigate the expression of vascular endothelial growth factor (VEGF) and calcium-binding protein S100A4 in pancreatic cancer and their relationship to the clinicopathological parameters and prognosis of pancreatic cancer.METHODS: Expression status of VEGF and S100A4 was examined in 62 surgical specimens of primary pancreatic cancer by immunohistochemistry. Correlation between the expression of VEGF and S100A4 and clinicopathological parameters was analyzed.RESULTS: Thirty-eight of 62 (61.3%) specimens of primary pancreatic cancer were positive for S100A4. Thirty-seven (59.7%) specimens showed positive expression of VEGF. The positive correlation between S100A4 and VEGF expression was significant in cancer tissues(P < 0.001). S100A4 expression was significantly correlated with tumor size, TNM stage and poorer prognosis. VEGF expression had a significant correlation with poorer prognosis. The prognosis of 17 S100A4- and VEGF-negative cancer patients was significantly better than that of other patients (P < 0.05). Distant metastasis(P = 0.001), S100A4- (P = 0.008) and VEGF-positive expression (P= 0.016) were significantly independent prognostic predictors (P<0.05).CONCLUSION: Over-expression of S100A4 and VEGF plays an important role in the development of pancreatic cancer. Combined examination of the two molecules might be useful in evaluating the outcome of patients with pancreatic cancer.

  20. Prognostic significance of smac/DIABLO in endometrioid endometrial cancer.

    Directory of Open Access Journals (Sweden)

    Magdalena Garbowicz

    2011-04-01

    Full Text Available Apoptosis may occur via a death receptor-dependent or independent (mitochondrial pathway. The mitochondrial pathway is regulated by small molecules, such as smac/Diablo, which activates caspase cascades. This study examined smac/DIABLO expression in 76 patients with endometrioid endometrial cancers. Presence of smac/DIABLO was quantified by Western blot analysis using nonfixed fresh frozen tissues. Its appearance was found in 55 (72% of examined tumors. Smac/DIABLO expression significantly correlated with tumor grade (p<0.001. Patients with positive smac/DIABLO tumors had a longer disease-specific survival when compared with those with negative tumors in the 10-year follow-up (p=0.043. The study demonstrated that negative smac/DIABLO expression was a poor prognostic sign.

  1. Prognostic significance of smac/DIABLO in endometrioid endometrial cancer

    Directory of Open Access Journals (Sweden)

    Bozena Dobrzycka

    2010-04-01

    Full Text Available Apoptosis may occur via a death receptor-dependent or independent (mitochondrial pathway. The mitochondrialpathway is regulated by small molecules, such as smac/Diablo, which activates caspase cascades. This study examinedsmac/DIABLO expression in 76 patients with endometrioid endometrial cancers. Presence of smac/DIABLO was quantifiedby Western blot analysis using nonfixed fresh frozen tissues. Its appearance was found in 55 (72% of examined tumors.Smac/DIABLO expression significantly correlated with tumor grade (p<0.001. Patients with positive smac/DIABLOtumors had a longer disease-specific survival when compared with those with negative tumors in the 10-year follow-up(p=0.043. The study demonstrated that negative smac/DIABLO expression was a poor prognostic sign.

  2. ROCK1 as a novel prognostic marker in vulvar cancer

    DEFF Research Database (Denmark)

    Akagi, Erica M; Lavorato-Rocha, André M; Maia, Beatriz de Melo;

    2014-01-01

    infection, but most cases develop in women aged over 50 years through poorly understood genetic mechanisms. Rho-associated coiled-coil-containing protein kinase 1 (ROCK1) has been implicated in many cellular processes, but its function in vulvar cancer has never been examined. In this study, we aimed to...... determine the prognostic value of ROCK1 gene and protein analysis in vulvar squamous cell carcinoma (VSCC). METHODS: ROCK1 expression levels were measured in 16 vulvar tumour samples and adjacent normal tissue by qRT-PCR. Further, 96 VSCC samples were examined by immunohistochemistry (IHC) to confirm the...... involvement of ROCK1 in the disease. The molecular and pathological results were correlated with the clinical data of the patients. Sixteen fresh VSCC samples were analyzed by array-based comparative genomic hybridization (aCGH). RESULTS: In each pair of samples, ROCK1 levels were higher by qRT-PCR in normal...

  3. Diagnostic accuracy and prognostic impact of restaging by magnetic resonance imaging after preoperative chemoradiotherapy in patients with rectal cancer

    International Nuclear Information System (INIS)

    Background: The prognostic role of restaging rectal magnetic resonance imaging (MRI) in patients with preoperative CRT has not been established. The goal of this study was to evaluate the diagnostic accuracy and prognostic role of radiological staging by rectal MRI after preoperative chemoradiation (CRT) in patients with rectal cancer. Methods: A total of 231 consecutive patients with rectal cancer who underwent preoperative CRT and radical resection from January 2008 to December 2009 were prospectively enrolled. The diagnostic accuracy and prognostic significance of post-CRT radiological staging by MRI was evaluated. Results: The sensitivity, specificity, positive predictive value, and negative predictive value of radiological diagnosis of good responders (ypTNM stage 0–I) were 32%, 90%, 65%, and 69%, respectively. The overall accuracy of MRI restating for good responders was 68%. The 5-year disease-free survival rates of patients with radiological and pathological TNM stage 0, stage I, and stage II–III were 100%, 94%, and 76%, respectively (P = 0.037), and 97%, 87%, and 73%, respectively (P = 0.007). On multivariate analysis, post-CRT radiological staging by MRI was an independent prognostic factor for disease-free survival. Conclusion: Radiological staging by MRI after preoperative CRT may be an independent predictor of survival in patients with rectal cancer

  4. Prognostic Values of microRNAs in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Yaguang Xi

    2006-01-01

    Full Text Available The functions of non-coding microRNAs (miRNAs in tumorigenesis are just beginning to emerge. Previous studies from our laboratory have identifi ed a number of miRNAs that were deregulated in colon cancer cell lines due to the deletion of the p53 tumor suppressor gene. In this study, the in vivo signifi cance of some of these miRNAs was further evaluated using colorectal clinical samples. Ten miRNAs (hsa-let-7b, hsa-let-7g, hsa-miR-15b, hsa-miR-181b, hsa-miR-191, hsa-miR-200c, hsa-miR-26a, hsa-miR-27a, hsa-miR-30a-5p and hsa-miR-30c were evaluated for their potential prognostic value in colorectal cancer patients. Forty eight snap frozen clinical colorectal samples (24 colorectal cancer and 24 paired normal patient samples with detailed clinical follow-up information were selected . The expression levels of 10 miRNAs were quantified via qRT-PCR analysis. The statistical signifi cance of these markers for disease prognosis was evaluated using a two tailed paired Wilcoxon test. A Kaplan-Meier survival curve was generated followed by performing a Logrank test. Among the ten miRNAs, hsa-miR-15b (p = 0.0278, hsa-miR-181b (p = 0.0002, hsa-miR-191 (p = 0.0264 and hsa-miR-200c (p = 0.0017 were signifi cantly over-expressed in tumors compared to normal colorectal samples. Kaplan-Meier survival analysis indicated that hsa-miR-200c was signifi cantly associated with patient survival (p = 0.0122. The patients (n = 15 with higher hsa-miR-200c expression had a shorter survival time (median survival = 26 months compared to patients (n = 9 with lower expression (median survival = 38 months. Sequencing analysis revealed that hsa-miR-181b (p = 0.0098 and hsa-miR-200c (p = 0.0322 expression were strongly associated with the mutation status of the p53 tumor suppressor gene. Some of these miRNAs may function as oncogenes due to their over-expression in tumors. hsa-miR-200c may be a potential novel prognostic factor in colorectal cancer.

  5. Prognostic value of breast cancer subtypes on breast cancer specific survival, distant metastases and local relapse rates in conservatively managed early stage breast cancer: a retrospective clinical study

    OpenAIRE

    Sanpaolo, Pietro; Barbieri, Viviana; Genovesi, Domenico

    2011-01-01

    International audience To ascertain if breast cancer subtypes had prognostic effect on breast cancer specific survival, distant metastases and local relapse rates in women affected by early stage breast cancer.

  6. Intact and cleaved uPAR forms: diagnostic and prognostic value in cancer

    DEFF Research Database (Denmark)

    Rasch, M.G.; Lund, I.K.; Hoyer-Hansen, G.;

    2008-01-01

    identified in tissue and body fluids. It is well-established, that the total amount of all uPAR forms is a strong prognostic marker in different types of cancer. Using immunoassays, measuring the individual uPAR forms, has revealed that the cleaved uPAR forms are even stronger prognostic markers and have...

  7. Preoperative plasma TIMP-1 is an independent prognostic indicator in patients with primary colorectal cancer

    DEFF Research Database (Denmark)

    Birgisson, Helgi; Nielsen, Hans J.; Christensen, Ib Jarle;

    2010-01-01

    Previous studies have suggested plasma tissue inhibitor of metalloproteinases-1 (TIMP-1) as a stage independent prognostic marker in colorectal cancer (CRC) patients. The aim was to validate plasma TIMP-1 and serum carcino-embryonic antigen (CEA) levels as prognostic indicators in an independent...... population-based cohort of patients with CRC....

  8. A six-microRNA set as prognostic indicators for bile duct cancer.

    Science.gov (United States)

    Wang, Ming; Wen, Tian-Fu; He, Lin-Hai; Li, Chuan; Zhu, Wen-Jiang; Trishul, Narasimha Murthy

    2015-01-01

    MicroRNAs (miRNAs) play important roles in cancer progression by altering transcriptional control. The purpose of this study is to identify and explore specific miRNAs as prognostic and predictive biomarkers for bile duct cancer (BDC) by analyzing Next-generation data. miRNA expression profiles and corresponding clinical information of BDC samples were extracted from The Cancer Genome Atlas (TCGA). The differentially expressed miRNAs were determined by SAMR package in R software. Target genes of those miRNAs were predicted by Targetscan. Functional enrichment analysis and hypergeometric test analysis of target genes were performed. Then, diagnosis accuracy of miRNAs was judged by ROC Curves analysis. Total 120 differentially expressed miRNAs were obtained, of which six important miRNAs were selected and predicted as prognosis and predicting biomarkers in BDC. Besides, functional analysis showed that both enriched pathways were significantly related with ion binding, which might involve in the carcinogenesis of BDC. Moreover, top 3 important pathways sharing the most influence were noted. Our results demonstrated that hsa-miR-483-5p, hsa-miR-675, hsa-miR-139-3p, hsa-miR-598, hsa-miR-625 and hsa-miR-187 could serve as prognostic and predictive markers for survival of BDC patients and could potentially be provided as targets for future therapy. PMID:26770318

  9. Improved prognostic classification of breast cancer defined by antagonistic activation patterns of immune response pathway modules

    International Nuclear Information System (INIS)

    Elucidating the activation pattern of molecular pathways across a given tumour type is a key challenge necessary for understanding the heterogeneity in clinical response and for developing novel more effective therapies. Gene expression signatures of molecular pathway activation derived from perturbation experiments in model systems as well as structural models of molecular interactions ('model signatures') constitute an important resource for estimating corresponding activation levels in tumours. However, relatively few strategies for estimating pathway activity from such model signatures exist and only few studies have used activation patterns of pathways to refine molecular classifications of cancer. Here we propose a novel network-based method for estimating pathway activation in tumours from model signatures. We find that although the pathway networks inferred from cancer expression data are highly consistent with the prior information contained in the model signatures, that they also exhibit a highly modular structure and that estimation of pathway activity is dependent on this modular structure. We apply our methodology to a panel of 438 estrogen receptor negative (ER-) and 785 estrogen receptor positive (ER+) breast cancers to infer activation patterns of important cancer related molecular pathways. We show that in ER negative basal and HER2+ breast cancer, gene expression modules reflecting T-cell helper-1 (Th1) and T-cell helper-2 (Th2) mediated immune responses play antagonistic roles as major risk factors for distant metastasis. Using Boolean interaction Cox-regression models to identify non-linear pathway combinations associated with clinical outcome, we show that simultaneous high activation of Th1 and low activation of a TGF-beta pathway module defines a subtype of particularly good prognosis and that this classification provides a better prognostic model than those based on the individual pathways. In ER+ breast cancer, we find that

  10. Detection of lymphangiogenesis in non-small cell lung cancer and its prognostic value

    Directory of Open Access Journals (Sweden)

    Liao Rong-xia

    2009-02-01

    Full Text Available Abstract Background Our aim was to detect lymphatic endothelial marker podoplanin, lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1 and vascular endothelial growth factor receptor-3 (VEGFR-3 and study the prognostic relevance of lymphangiogenesis in non-small cell lung cancer (NSCLC. Materials 82 paraffin-embedded tissues and 40 fresh frozen tissues from patients with NSCLC were studied. Tumor samples were immunostained for the lymphatic endothelial markers. Lymphangiogenesis was assessed by immunohistochemical double stains for Podoplanin and Ki-67. The prognostic relevance of lymphangiogenesis-related clinicopathological parameters in NSCLC was evaluated. Results We found that the number of podoplanin positive vessels was correlated positively with the number of LYVE-1 positive vessels. Most of VEGFR-3 positive, few of LYVE-1 positive and none of podoplanin positive vessels were blood vessels. Peritumoral lymphatic vessel density (ptLVD, pathologic stage, lymph node status, lymphatic vessel invasion (LVI, vascular endothelial growth factor-C (VEGF-C expression and Ki-67 index of the endothelium cells of the micro lymphatic vessels (Ki67% were associated significantly with a higher risk of tumor progress. ptLVD, pathologic stage, lymph-node metastasis and Ki67% were independent prognostic parameters for overall survival. Conclusion Podoplanin positive ptLVD might play important roles in the lymphangiogenesis and progression of NSCLC. Patients with high podoplanin+ ptLVD have a poor prognosis.

  11. Diameter of involved nerves is a valuable prognostic factor for gastric cancer.

    Science.gov (United States)

    Zhou, Zhi-hua; Zhang, Jian-dong; Zhao, Hai-Bin; Wu, Yao-yi

    2015-09-01

    The prognostic role of perineural invasion (PNI) in gastric cancer remains unclear. We hypothesized that the diameter of the tumor-involved nerves might be a useful indicator for prognosis. By labeling nerves and cancer cells in 204 cases of gastric cancer with single or double immunochemistry, we found that 146 cases were PNI positive and that 58 were PNI negative. For each case with PNI, the maximum diameter of the involved nerve was measured microscopically. Then, we correlated this parameter with the patients' 5-year overall survival, and receiver operating curves were used to determine the cutoff value. We found that the optimal cutoff value for predicting 5-year survival was 65 µm (sensitivity 76.9%, specificity 70.0%). Next, all 204 patients were classified into two groups as follows: Group A, PNI-positive cases in which the largest involved nerves were ≥65 µm in diameter (110 cases); Group B, PNI-positive cases in which the largest involved nerves were P˂65 µm and all PNI-negative cases (94 cases). Compared with Group A, Group B had a better 5-year survival (74.5% vs 27.3%) and a better 5-year disease-free survival (63.8% vs 23.6%). Multivariate analysis suggested that a ≥65 µm maximum diameter of the involved nerves was an independent risk factor for both recurrence (P˂0.001) and gastric cancer-related death (P˂0.001) within 5 years. However, if all patients were classified simply based on whether PNI existed (regardless of the nerve size), this did not provide more information than traditional clinicopathological variables. In conclusion, the presence of cancer-involved nerves with a diameter ≥65 µm was a valuable prognostic factor for gastric cancer. PMID:25791836

  12. The prognostic role of 99mTc-MDP breast scintigraphy. Comparison of scintigrafic findings with histologic and molecular parameters

    International Nuclear Information System (INIS)

    Breast scintigraphy (BS) with the bone-seeking agent 99mTc-medronate (MDP) can be usefully combined with mammography to diagnose and characterize questionable breast lumps. However this radiotracer does not seem to provide any further prognostic information about breast cancer. Therefore it is investigated the prognostic yield of MDP-BS searching for correlations between scintigraphic findings and the major biological and histologic parameters. It is retrospectively analyzed a series of 44 primary breast cancers. All patients had undergone 99mTc-MDP bone scan for preoperative staging, as well as conventional breast imaging. It is statistically compared the cancer/background ratio (c/b index) with lesion histotype, diameter, grading, and the tissue concentrations of steroid receptors, cathepsine D, type 1 timidine kinase, pS2 and p53 proteins). Differently from BS with 99mTc-MIBI, 201Tl, 18F-FDG, 111In-OCT and radiolabeled estrogens and despite its good overall accuracy, MDP-BS appears to have no prognostic role. In fact, despite the well-known capability of soft tissue lesions to take up the tracer, MDP tumor trapping seems to depend mainly on the increased permeability of neo vessels and on interstitial space enlargement. Few reports are available in the literature on the correlation between in vivo MDP uptake by the breast cancer and prognostic parameters. Thus, it are tested possible correlations between the amount of MDP taken up by the breast cancer, histologic features and cell concentrations of some major biomarkers. The lack of any statistical significance is in agreement with the theory, and confirms the little prognostic value of MDP-BS. Nevertheless, further trials are warranted on larger series of cases to validate personal findings

  13. Emerging roles of orphan nuclear receptors in cancer.

    Science.gov (United States)

    Baek, Sung Hee; Kim, Keun Il

    2014-01-01

    A growing body of evidence suggests that a subset of orphan nuclear receptors are amplified and prognostic for some human cancers. However, the specific roles of these orphan nuclear receptors in tumor progression and their utility as drug targets are not fully understood. In this review, we summarize recent progress in elucidating the direct and indirect involvement of orphan nuclear receptors in cancer as well as their therapeutic potential in a variety of human cancers. Furthermore, we contrast the role of orphan nuclear receptors in cancer with the known roles of estrogen receptor and androgen receptor in hormone-dependent cancers. PMID:24215441

  14. Prognostic importance of VEGF-A haplotype combinations in a stage II colon cancer population

    DEFF Research Database (Denmark)

    Kjaer-Frifeldt, Sanne; Fredslund, Rikke; Lindebjerg, Jan; Hansen, Torben Froestrup; Spindler, Karen-Lise Garm; Jakobsen, Anders

    2012-01-01

    To investigate the prognostic effect of three VEGF-A SNPs, -2578, -460 and 405, as well as the corresponding haplotype combinations, in a unique population of stage II colon cancer patients.......To investigate the prognostic effect of three VEGF-A SNPs, -2578, -460 and 405, as well as the corresponding haplotype combinations, in a unique population of stage II colon cancer patients....

  15. The Prognostic Significance of Apoptosis-Related Biological Markers in Chinese Gastric Cancer Patients

    OpenAIRE

    Liu, Xiaowen; Cai, Hong; Huang, Hua; Long, Ziwen; Shi, Yingqiang; Wang, Yanong

    2011-01-01

    Background and Objective The prognosis varied among the patients with the same stage, therefore there was a need for new prognostic and predictive factors. The aim of this study was to evaluate the relationship of apoptosis-related biological markers such as p53, bcl-2, bax, and c-myc, and clinicopathological features and their prognostic value. Methods From 1996 to 2007, 4426 patients had undergone curative D2 gastrectomy for gastric cancer at Fudan University Shanghai Cancer Center. Among 5...

  16. A Nomogram to Predict Prognostic Value of Red Cell Distribution Width in Patients with Esophageal Cancer

    OpenAIRE

    Gui-Ping Chen; Ying Huang; Xun Yang; Ji-Feng Feng

    2015-01-01

    Objectives. The prognostic value of inflammatory index in esophageal cancer (EC) was not established. In the present study, we initially used a nomogram to predict prognostic value of red cell distribution width (RDW) in patients with esophageal squamous cell carcinoma (ESCC). Methods. A total of 277 ESCC patients were included in this retrospective study. Kaplan-Meier method was used to calculate the cancer-specific survival (CSS). A nomogram was established to predict the prognosis for CSS....

  17. Treatment Results and prognostic Factors in Patients with Esophageal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Weon Kuu; Kim, Soo Kon; Kim, Min Chul; Jang, Myoung [Presbyterian Medical Center, Chonju (Korea, Republic of); Moon, Sun Rock [Wonkwang Univ., Medical School, Iksan (Korea, Republic of)

    1995-09-15

    Purpose : To analyse clinical outcome and prognostic factors according to treatment modality, this paper report our experience of retrospective study of patients with esophageal cancer. Materials and Methods : One hundred and ten patients with primary esophageal cancer who were treated in Presbyterian Medical Center from May 1985 to December 1992. We analysed these patients retrospectively with median follow up time of 28 months, one hundred and four patients(95%) were followed up from 15 to 69 months. In methods, twenty-eight patients were treated with median radiation dose irradiated 54.3Gy only. Fifty-six patients were treated with combined chemoradiotherapy. Sixteen cases of these patients were treated with concurrent chemoradiation and the other patients(forty cases) were treated sequential chemoradiotherapy. In concurrent chemoradiotherapy group, patients received 5-FU continuous IV infusion for 4 days. Cisplatin IV bolus, and concurrent esophageal irradiation to 30 Gy. After that patients received ?Fu continuous IV, Cisplatin bolus injection and Mitomycin-C bolus IV, Bleomycin continuous IV, and irradiation to 20 Gy. In sequential chemoradiotherapy group, the chemotherapy consisted of 5-FU 1,000 mg/m2 administered as a continuous 24 hour intravenous infusion during five days and Cisplatin 80-100 mg/m2 bolus injected, or Bleomycin, Vinblastine, Cisplatin, Methotrexate were used of 1 or 2 cycles. After preoperative concurrent chemoradiation, twenty-six patients underwent radical esophagectomy. Results ; ninety-three patients could be examined for response assessment. By treatment modality, response rates were 85.1% for radiation alone group and 86.3% for combined chemoradiation group. But in operation group, after one cycle of concurrent chemoradiation treatment, response rate was 61.9%. The pathologic complete response were 15.4% in operation group. Overall median survival was 11 months and actuarial 5-year survival rate was 8%. The median survival interval

  18. XAF1 as a prognostic biomarker and therapeutic target in squamous cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    CHEN Yong-bing; SHU Jian; YANG Wen-tao; SHI Li; GUO Xu-feng; WANG Fei-ge; QIAN Yong-yue

    2011-01-01

    Background X-linked inhibitor of apoptosis (XIAP)-associated factor 1 (XAF1) is a new tumor suppressor.Low expression of XAF1 is associated with poor prognosis of human cancers.However,the effect of XAF1 on lung cancerremains unknown.In this study,we investigated the expression of XAF1 and its role in squamous cell lung cancer.Methods Cancer tissues,cancer adjacent tissues and normal lung tissues were collected from 51 cases of squamous cell lung cancer.The expression of XAF1 mRNA was determined by reverse transcription-polymerase chain reaction (RT-PCR).The expression of XAF1 protein was determined by Western blotting and immunohistochemical staining.Ad5/F35-XAF1 virus was generated.Cell proliferation and apoptosis were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method and flow cytometry (FACS),respectively.Results The levels of XAF1 protein and mRNA in cancer tissues were significantly lower than those in cancer adjacent and normal lung tissues (P <0.05).The low expression of XAF1 was associated with tumor grade,disease stage,differentiation status and lymph node metastasis in squamous cell lung cancer patients.The restoration of XAF1 expression mediated by Ad5/F35-XAF1 virus significantly inhibited cell proliferation and induced apoptosis in a dose- and time-dependent manner.Conclusion XAF1 is a valuable prognostic marker in squamous cell lung cancer and may be a potential candidate gene for lung cancer therapy.

  19. NDRG4 stratifies the prognostic value of body mass index in colorectal cancer.

    Science.gov (United States)

    Zheng, Jianyong; Li, Yunming; Zhu, Shaojun; Li, Jipeng; Zhao, Qingchuan; Ji, Gang; Wang, Weizhong; Chu, Dake

    2016-01-12

    NDRG4 is a novel candidate tumor suppressor and can inhibit PI3K/AKT signal which is related with energy balance and related carcinogenesis. In the present study, we investigated whether NDRG4 status could modify the association of obesity with clinical outcome of colorectal cancer. For this purpose, a hospital-based prospective study cohort of 226 colorectal cancer patients was involved. NDRG4 mRNA levels were determined by real-time PCR. Association of NDRG4 mRNA expression with disease-free and overall survival was studied first. Then, the association of obesity with clinical outcome was determined according to NDRG4 level. Multivariate Cox proportional hazards model was used to compute hazard ratio, adjusting for covariates including microsatellite instability, KRAS, BRAF and PIK3CA mutation. Results showed that NDRG4 mRNA expression was decreased in tumor specimens and significantly correlated with tumor differentiation, invasion and metastasis. Patients with tumor of reduced NDRG4 mRNA level had unfavorable disease-free and overall survival. Obesity was found to be adversely associated with disease-free and overall survival in tumors with reduced NDRG4 level, not in preserved NDRG4 level group, in both univariate and multivariate analysis. These data provided the first evidence that NDRG4 level in colorectal cancer could effectively stratify the prognostic value of obesity, which would better the understanding of the prognostic role of obesity in colorectal cancer. Our results also support the notion that the host-tumor interactions in colorectal cancer might influence tumor aggressiveness. PMID:26515606

  20. New Breast Cancer Recursive Partitioning Analysis Prognostic Index in Patients With Newly Diagnosed Brain Metastases

    International Nuclear Information System (INIS)

    Purpose: The aim of the study was to present a new breast cancer recursive partitioning analysis (RPA) prognostic index for patients with newly diagnosed brain metastases as a guide in clinical decision making. Methods and Materials: A prospectively collected group of 441 consecutive patients with breast cancer and brain metastases treated between the years 2003 and 2009 was assessed. Prognostic factors significant for univariate analysis were included into RPA. Results: Three prognostic classes of a new breast cancer RPA prognostic index were selected. The median survival of patients within prognostic Classes I, II, and III was 29, 9, and 2.4 months, respectively (p < 0.0001). Class I included patients with one or two brain metastases, without extracranial disease or with controlled extracranial disease, and with Karnofsky performance status (KPS) of 100. Class III included patients with multiple brain metastases with KPS of ≤60. Class II included all other cases. Conclusions: The breast cancer RPA prognostic index is an easy and valuable tool for use in clinical practice. It can select patients who require aggressive treatment and those in whom whole-brain radiotherapy or symptomatic therapy is the most reasonable option. An individual approach is required for patients from prognostic Class II.

  1. Prognostic significance of RNA-dependent protein kinase (PKR) on non-small cell lung cancer patients

    Science.gov (United States)

    Pataer, Abujiang; Raso, Maria Gabriela; Correa, Arlene M; Behrens, Carmen; Tsuta, Koji; Solis, Luisa; Fang, Bingliang; Roth, Jack A.; Wistuba, Ignacio I.; Swisher, Stephen G.

    2011-01-01

    Purpose The role of RNA-dependent protein kinase (PKR) in antiviral defence mechanisms and in cellular differentiation, growth, and apoptosis is well known, but the role of PKR in human lung cancer remains poorly understood. To explore the role of PKR in human lung cancer, we evaluated PKR’s expression in tissue microarray specimens from both non-small cell lung cancer (NSCLC) and normal human bronchial epithelium tissue. Experimental Design Tissue microarray samples (TMA-1) from 231 lung cancers were stained with PKR antibody and validated on TMA-2 from 224 lung cancers. Immunohistochemical expression score was quantified by three pathologists independently. Survival probability was computed by the Kaplan-Meier method. Results The NSCLC cells showed lower levels of PKR expression than normal bronchial epithelium cells did. We also found a significant association between lower levels of PKR expression and lymph node metastasis. We found that loss of PKR expression is correlated with a more aggressive behavior, and that a high PKR expression predicts a subgroup of patients with a favorable outcome. Univariate and multivariate Cox proportional hazards regression models showed that a lower level of PKR expression was significantly associated with shorter survival in NSCLC patients. We further validated and confirmed that PKR to be a powerful prognostic factor in TMA-2 lung cancer (HR=0.22, P<0.0001). Conclusions Our findings first indicate that PKR expression is an independent prognostic variable in NSCLC patients. PMID:20930042

  2. Periostin Expression and Its Prognostic Value for Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Zewu Li

    2015-05-01

    Full Text Available Integrin is important for cell growth, invasion and metastasis, which are frequently observed in malignant tumors. The periostin (POSTN gene encodes the ligand for integrin, one of the key focal adhesion proteins contributing to the formation of a structural link between the extracellular matrix and integrins. High expression levels of the POSTN gene are correlated with numerous human malignancies. We examined POSTN protein in colorectal cancer specimens from 115 patients by strictly following up using immunohistochemistry. Cytoplasm immunohistochemical staining showed POSTN protein expression in colorectal cancers. The positive expression rate of POSTN protein (59.13%, 68/115 in colorectal cancers was significantly higher than that in adjacent normal colon mucosa (0.47%, 11/109. POSTN over-expression in colorectal cancers was positively correlated with tumor size, differentiation, lymph node metastasis, serosal invasion, clinical stage and five-year survival rates. Further analysis showed that patients with advanced stage colorectal cancer and high POSTN expression levels had lower survival rates than those with early stage colorectal cancer and low POSTN expression levels. Overall, our results showed that POSTN played an important role in the progression of colorectal cancers.

  3. Molecular markers for detection, surveillance and prognostication of bladder cancer.

    NARCIS (Netherlands)

    Vrooman, O.P.; Witjes, J.A.

    2009-01-01

    Many markers for the detection of bladder cancers have been tested and almost all urinary markers reported are better than cytology with regard to sensitivity, but they score lower in specificity. Currently molecular and genetic changes play an important role in the discovery of new molecular marker

  4. PROGNOSTIC FACTORS OF PROSTATE CANCER BEFORE AND AFTER RADICAL PROSTATECTOMY

    Directory of Open Access Journals (Sweden)

    E. I. Veliev

    2014-07-01

    Full Text Available Objective: to assess a correlation between the preoperative prognostic characteristics and the pathologic stage and to determine whether a positive surgical margin is present after radical prostatectomy (RPE.Materials and methods. The materials of 224 patients with prostate cancer (PC who had undergone RPE at the Clinic of Urology and Surgical Andrology, Russian Medical Academy of Postgraduate Education, were analyzed.Results. The patients’ median age was 62 (43–78 years. Sixty-seven (29.9 %, 46 (20.5%, and 111 (49.6 % patients were referred to as low-, moderate-, and high-risk groups, respectively. A positive surgical margin was observed in 11.9, 28.3, and 38.7 % of the patients in the low-, moderate-, and high-risk groups, respectively (р = 0.0003. The predictors of a positive surgical margin were the percent of involved biopsy specimens (R = 0.34 and Gleason score (R = 0.31 and perineural invasion. According to multivariate analysis, neither the preoperative level of prostate-specific antigen, nor the clinical stage showed any correlation with the positive surgical margin and the pathologic stage after RPE.

  5. Prognostic factors in the estimation of HIFU treatment efficiency in patients with localized prostate cancer

    Directory of Open Access Journals (Sweden)

    Popkov V.M.

    2013-03-01

    Full Text Available Research objective: To study the role of prognostic factors in the estimation of risk development of recurrent prostate cancer after treatment by high-intensive focused ultrasound (HIUF. Objects and Research Methods: The research has included 102 patients with morphologically revealed localized prostate cancer by biopsy. They have been on treatment in Clinic of Urology of the Saratov Clinical Hospital n.a. S. R. Mirotvortsev. 102 sessions of initial operative treatment of prostate cancer by the method of HIFU have been performed. The general group of patients (n=102 has been subdivided by the method of casual distribution into two samples: group of patients with absent recurrent tumor and group of patients with the revealed recurrent tumor, by morphological research of biopsy material of residual prostate tissue after HIFU. The computer program has been used to study the signs of outcome of patients with prostate cancer. Results: Risk of development of recurrent prostate cancer has grown with the PSA level raise and its density. The index of positive biopsy columns <0,2 has shown the recurrence of prostate cancer in 17% cases while occurrence of prostate cancer in 59% cases has been determined by the index of 0,5 and higher. The tendency to obvious growth of number of relapses has been revealed by the sum of Glison raise with present perineural invasion. Cases of recurrent prostate cancer have been predominant in patients with lymphovascular invasions. In conclusion it has been worked out that the main signs of recurrent prostate cancer development may include: PSA, PSA density, the sum of Glison, lymphovascular invasion, invasion.

  6. Multifocality as a prognostic factor in breast cancer patients registered in Danish Breast Cancer Cooperative Group (DBCG) 1996-2001

    DEFF Research Database (Denmark)

    Joergensen, L.E.; Gunnarsdottir, K.A.; Lanng, C.;

    2008-01-01

    The purpose of this study was to investigate the prognostic influence of multifocality in breast cancer patients. In a cohort of 7196 patients there were 945 patients with multifocality. We found no prognostic influence of multifocality on overall survival when controlling for known prognostic......, Gunnarsdottir KA, Rasmussen BB, Moeller S, Lanng C. The prognostic influence of multifocality in breast cancer patients. Breast 2004;13:188-193]....... factors. We found a small but significant influence on disease-free survival (HR=1.16 [1.03-1.31]) and a strong correlation between multifocality and known prognostic factors. This was in accordance with an earlier study done on a smaller population and in a different period of time [Pedersen L...

  7. Kinesin family member 14: an independent prognostic marker and potential therapeutic target for ovarian cancer.

    Science.gov (United States)

    Thériault, Brigitte L; Pajovic, Sanja; Bernardini, Marcus Q; Shaw, Patricia A; Gallie, Brenda L

    2012-04-15

    The novel oncogene KIF14 (kinesin family member 14) shows genomic gain and overexpression in many cancers including OvCa (ovarian cancer). We discovered that expression of the mitotic kinesin KIF14 is predictive of poor outcome in breast and lung cancers. We now determine the prognostic significance of KIF14 expression in primary OvCa tumors, and evaluate KIF14 action on OvCa cell tumorigenicity in vitro. Gene-specific multiplex PCR and real-time QPCR were used to measure KIF14 genomic (109 samples) and mRNA levels (122 samples) in OvCa tumors. Association of KIF14 with clinical variables was studied using Kaplan-Meier survival and Cox regression analyses. Cellular effects of KIF14 overexpression (stable transfection) and inhibition (stable shRNA knockdown) were studied by proliferation (cell counts), survival (Annexin V immunocytochemistry) and colony formation (soft-agar growth). KIF14 genomic gain (>2.6 copies) was present in 30% of serous OvCas, and KIF14 mRNA was elevated in 91% of tumors versus normal epithelium. High KIF14 in tumors independently predicted for worse outcome (p = 0.03) with loss of correlation with proliferation marker expression and increased rates of recurrence. Overexpression of KIF14 in OvCa cell lines increased proliferation and colony formation (p < 0.01), whereas KIF14 knockdown induced apoptosis and dramatically reduced colony formation (p < 0.05). Our findings indicate that KIF14 mRNA is an independent prognostic marker in serous OvCa. Dependence of OvCa cells on KIF14 for maintenance of in vitro colony formation suggests a role of KIF14 in promoting a tumorigenic phenotype, beyond its known role in proliferation. PMID:21618518

  8. Prognostic Value of Preoperative Serum Levels of Periostin (PN in Early Breast Cancer (BCa

    Directory of Open Access Journals (Sweden)

    Pier Vitale Nuzzo

    2015-07-01

    Full Text Available PN is a secreted cell adhesion protein critical for carcinogenesis. Elevated serum levels of PN have been implicated as playing an important role in different types of cancer, and a few reports suggest a potential role as a prognostic marker. We evaluated the prognostic significance of preoperative serum PN concentration in patients with BCa receiving curative surgery. Enzyme-Linked Immunosorbent Assay (ELISA was performed to determine the preoperative serum PN level in 182 patients. The correlations between serum PN concentration with clinical pathological features and PN expression in primary tumor samples were analyzed. The prognostic impact of serum PN levels with all-cause and BCa-specific mortality was also investigated. Appropriate statistics were used. Elevated serum PN levels were significantly associated with patient age (p = 0.005, adjuvant systemic therapy (p = 0.04 and progesterone receptor (PgR status (p = 0.02. No correlation between PN preoperative serum levels and other clinical-pathological parameters, including either the epithelial or the stromal PN expression of primary tumor or the combination of the two, was found. Similarly, no association between serum PN levels and either all-cause or BCa-specific mortality was found. However, subgroup analysis revealed a correlation between higher PN serum levels and all-cause mortality in patients with node-negative disease (p = 0.05 and in those with a low PgR expression (p = 0.03. Higher levels of serum PN were also found to correlate with BCa-specific mortality in the subgroup of patients who did not receive any adjuvant systemic therapy (p = 0.04. Our findings suggest that PN was detectable in the serum of early BCa patients before surgery and increased base-line serum levels predicted worse long-term survival outcomes in specific subgroups of patients.

  9. Prognostic Value of Preoperative Serum Levels of Periostin (PN) in Early Breast Cancer (BCa).

    Science.gov (United States)

    Nuzzo, Pier Vitale; Rubagotti, Alessandra; Argellati, Francesca; Di Meglio, Antonio; Zanardi, Elisa; Zinoli, Linda; Comite, Paola; Mussap, Michele; Boccardo, Francesco

    2015-01-01

    PN is a secreted cell adhesion protein critical for carcinogenesis. Elevated serum levels of PN have been implicated as playing an important role in different types of cancer, and a few reports suggest a potential role as a prognostic marker. We evaluated the prognostic significance of preoperative serum PN concentration in patients with BCa receiving curative surgery. Enzyme-Linked Immunosorbent Assay (ELISA) was performed to determine the preoperative serum PN level in 182 patients. The correlations between serum PN concentration with clinical pathological features and PN expression in primary tumor samples were analyzed. The prognostic impact of serum PN levels with all-cause and BCa-specific mortality was also investigated. Appropriate statistics were used. Elevated serum PN levels were significantly associated with patient age (p = 0.005), adjuvant systemic therapy (p = 0.04) and progesterone receptor (PgR) status (p = 0.02). No correlation between PN preoperative serum levels and other clinical-pathological parameters, including either the epithelial or the stromal PN expression of primary tumor or the combination of the two, was found. Similarly, no association between serum PN levels and either all-cause or BCa-specific mortality was found. However, subgroup analysis revealed a correlation between higher PN serum levels and all-cause mortality in patients with node-negative disease (p = 0.05) and in those with a low PgR expression (p = 0.03). Higher levels of serum PN were also found to correlate with BCa-specific mortality in the subgroup of patients who did not receive any adjuvant systemic therapy (p = 0.04). Our findings suggest that PN was detectable in the serum of early BCa patients before surgery and increased base-line serum levels predicted worse long-term survival outcomes in specific subgroups of patients. PMID:26225965

  10. Role of blood grouping as a prognostic marker in breast carcinoma its relationship with histological and hormonal prognostic markers

    Directory of Open Access Journals (Sweden)

    Lokesh Haswani

    2014-01-01

    Full Text Available Context: Breast carcinomas are one of the leading causes of mortality and morbidity in our country. Estrogen receptor (ER and progesterone receptor (PR status plays a very important role in therapeutic decisions in managing these patients. ABO and Rh blood type has been associated with risk and survival for several malignancies. Aims and Objectives: To know the frequency of ER and PR positivity status in the semi-urban population. To relate ABO/Rh blood group, ER and PR status with histopathological stage and Nottingham prognostic index (NPI. Materials and Methods: This was a retrospective study carried out on 45 cases from July 2012 to December 2013 who underwent mastectomy for breast cancer were included in our study. Histopathological grade of the tumor, lymph node invasion was noted. NPI was calculated. Immunohistochemistry was done using antibodies against ER and PR. Blood grouping and Rh typing was done. Descriptive statistics and Chi-square tests were done using SPSS package 20. P < 0.05 was considered to be significant. Results: In our study, maximum number of cases were in the fourth decade of life with a mean age of 52 years. ER and PRs were positive in 23/45 (51.1% of cases. Most of the ER and PR negative patients were in the premenopausal group. Lymph node-positive tumors were ER negative (54% and PR negative (58%. Patients in our study belonged to Group B (35.5% and Group O (35.5%. Eighty percent of Rh negative cases were ER and PR positive. A 2 × 2 table correlating ER and PR positivity with Rh negative status revealed a positive correlation with P < 0.05. Majority of ER and PR negative tumors belonged to Groups B and O. Conclusion: Majority of the patients were in premenopausal age group with 51.1% of our cases were ER and PR positive. Majority of Rh negative17 patients were ER and PR positive.

  11. Marcadores moleculares no câncer de pulmão: papel prognóstico e sua relação com o tabagismo Molecular markers in lung cancer: prognostic role and relationship to smoking

    Directory of Open Access Journals (Sweden)

    Ricardo Luiz de Menezes Duarte

    2006-02-01

    regarding prognostic value or therapeutic efficacy. Treatment strategies to cure lung cancer should focus on these early genetic lesions in order to promote their repair or to eliminate these lung cancer cells.

  12. Prognostic significance of MCM2, Ki-67 and gelsolin in non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Huberman Joel

    2006-08-01

    Full Text Available Abstract Background Uncontrolled proliferation and increased motility are hallmarks of neoplastic cells, therefore markers of proliferation and motility may be valuable in assessing tumor progression and prognosis. MCM2 is a member of the minichromosome maintenance (MCM protein family. It plays critical roles in the initiation of DNA replication and in replication fork movement, and is intimately related to cell proliferation. Ki-67 is a proliferation antigen that is expressed during all but G0 phases of the cell cycle. Gelsolin is an actin-binding protein that regulates the integrity of the actin cytoskeletal structure and facilitates cell motility. In this study, we assessed the prognostic significance of MCM2 and Ki-67, two markers of proliferation, and gelsolin, a marker of motility, in non-small cell lung cancer (NSCLC. Methods 128 patients with pathologically confirmed, resectable NSCLC (stage I-IIIA were included. Immunohistochemistry was utilized to measure the expressions of these markers in formalin-fixed, paraffin-embedded tumor tissues. Staining and scoring of MCM2, Ki-67 and gelsolin was independently performed. Analyses were performed to evaluate the prognostic significance of single expression of each marker, as well as the prognostic significance of composite expressions of MCM2 and gelsolin. Cox regression and Kaplan-Meier survival analysis were used for statistical analysis. Results Of the three markers, higher levels of gelsolin were significantly associated with an increased risk of death (adjusted RR = 1.89, 95% CI = 1.17–3.05, p = 0.01, and higher levels of MCM2 were associated with a non-significant increased risk of death (adjusted RR = 1.36, 95% CI = 0.84–2.20, p = 0.22. Combined, adjusted analyses revealed a significantly poor prognostic effect for higher expression of MCM2 and gelsolin compared to low expression of both biomarkers (RR = 2.32, 95% CI = 1.21–4.45, p = 0.01. Ki-67 did not display apparent prognostic

  13. Prognostic significance of MCM2, Ki-67 and gelsolin in non-small cell lung cancer

    International Nuclear Information System (INIS)

    Uncontrolled proliferation and increased motility are hallmarks of neoplastic cells, therefore markers of proliferation and motility may be valuable in assessing tumor progression and prognosis. MCM2 is a member of the minichromosome maintenance (MCM) protein family. It plays critical roles in the initiation of DNA replication and in replication fork movement, and is intimately related to cell proliferation. Ki-67 is a proliferation antigen that is expressed during all but G0 phases of the cell cycle. Gelsolin is an actin-binding protein that regulates the integrity of the actin cytoskeletal structure and facilitates cell motility. In this study, we assessed the prognostic significance of MCM2 and Ki-67, two markers of proliferation, and gelsolin, a marker of motility, in non-small cell lung cancer (NSCLC). 128 patients with pathologically confirmed, resectable NSCLC (stage I-IIIA) were included. Immunohistochemistry was utilized to measure the expressions of these markers in formalin-fixed, paraffin-embedded tumor tissues. Staining and scoring of MCM2, Ki-67 and gelsolin was independently performed. Analyses were performed to evaluate the prognostic significance of single expression of each marker, as well as the prognostic significance of composite expressions of MCM2 and gelsolin. Cox regression and Kaplan-Meier survival analysis were used for statistical analysis. Of the three markers, higher levels of gelsolin were significantly associated with an increased risk of death (adjusted RR = 1.89, 95% CI = 1.17–3.05, p = 0.01), and higher levels of MCM2 were associated with a non-significant increased risk of death (adjusted RR = 1.36, 95% CI = 0.84–2.20, p = 0.22). Combined, adjusted analyses revealed a significantly poor prognostic effect for higher expression of MCM2 and gelsolin compared to low expression of both biomarkers (RR = 2.32, 95% CI = 1.21–4.45, p = 0.01). Ki-67 did not display apparent prognostic effect in this study sample. The results suggest

  14. Androgen Receptor Expression in Early Triple-Negative Breast Cancer: Clinical Significance and Prognostic Associations

    Directory of Open Access Journals (Sweden)

    Mirco Pistelli

    2014-06-01

    Full Text Available Background: Triple-negative breast cancers (TNBC are characterized by aggressive tumour biology resulting in a poor prognosis. Androgen receptor (AR is one of newly emerging biomarker in TNBC. In recent years, ARs have been demonstrated to play an important role in the genesis and in the development of breast cancer, although their prognostic role is still debated. In the present study, we explored the correlation of AR expression with clinical, pathological and molecular features and its impact on prognosis in early TNBC. Patients and Methods: ARs were considered positive in case of tumors with >10% nuclear-stained. Survival distribution was estimated by the Kaplan Meier method. The univariate and multivariate analyses were performed. The difference among variables were calculated by chi-square test. Results: 81 TNBC patients diagnosed between January 2006 and December 2011 were included in the analysis. Slides were stained immunohistochemically for estrogen and progesterone receptors, HER-2, Ki-67, ALDH1, e-cadherin and AR. Of the 81 TNBC samples, 18.8% showed positive immunostaining for AR, 23.5% and 44.4% of patients were negative for e-cadherin and ALDH1, respectively. Positive AR immunostaining was inversely correlated with a higher Ki-67 (p < 0.0001 and a lympho-vascular invasion (p = 0.01, but no other variables. Univariate survival analysis revealed that AR expression was not associated with disease-free survival (p = 0.72 or overall survival (p = 0.93. Conclusions: The expression of AR is associated with some biological features of TNBC, such as Ki-67 and lympho-vascular invasion; nevertheless the prognostic significance of AR was not documented in our analysis. However, since ARs are expressed in a significant number of TNBC, prospective studies in order to determine the biological mechanisms and their potential role as novel treatment target.

  15. Androgen Receptor Expression in Early Triple-Negative Breast Cancer: Clinical Significance and Prognostic Associations

    Energy Technology Data Exchange (ETDEWEB)

    Pistelli, Mirco, E-mail: mirco.pistelli@alice.it; Caramanti, Miriam [Clinica di Oncologia Medica, AO Ospedali Riuniti-Ancona, Università Politecnica delle Marche, Ancona 60020 (Italy); Biscotti, Tommasina; Santinelli, Alfredo [Anatomia Patologica, AO Ospedali Riuniti-Ancona, Università Politecnica delle Marche, Ancona 60020 (Italy); Pagliacci, Alessandra; De Lisa, Mariagrazia; Ballatore, Zelmira; Ridolfi, Francesca; Maccaroni, Elena; Bracci, Raffaella; Berardi, Rossana; Battelli, Nicola; Cascinu, Stefano [Clinica di Oncologia Medica, AO Ospedali Riuniti-Ancona, Università Politecnica delle Marche, Ancona 60020 (Italy)

    2014-06-27

    Background: Triple-negative breast cancers (TNBC) are characterized by aggressive tumour biology resulting in a poor prognosis. Androgen receptor (AR) is one of newly emerging biomarker in TNBC. In recent years, ARs have been demonstrated to play an important role in the genesis and in the development of breast cancer, although their prognostic role is still debated. In the present study, we explored the correlation of AR expression with clinical, pathological and molecular features and its impact on prognosis in early TNBC. Patients and Methods: ARs were considered positive in case of tumors with >10% nuclear-stained. Survival distribution was estimated by the Kaplan Meier method. The univariate and multivariate analyses were performed. The difference among variables were calculated by chi-square test. Results: 81 TNBC patients diagnosed between January 2006 and December 2011 were included in the analysis. Slides were stained immunohistochemically for estrogen and progesterone receptors, HER-2, Ki-67, ALDH1, e-cadherin and AR. Of the 81 TNBC samples, 18.8% showed positive immunostaining for AR, 23.5% and 44.4% of patients were negative for e-cadherin and ALDH1, respectively. Positive AR immunostaining was inversely correlated with a higher Ki-67 (p < 0.0001) and a lympho-vascular invasion (p = 0.01), but no other variables. Univariate survival analysis revealed that AR expression was not associated with disease-free survival (p = 0.72) or overall survival (p = 0.93). Conclusions: The expression of AR is associated with some biological features of TNBC, such as Ki-67 and lympho-vascular invasion; nevertheless the prognostic significance of AR was not documented in our analysis. However, since ARs are expressed in a significant number of TNBC, prospective studies in order to determine the biological mechanisms and their potential role as novel treatment target.

  16. Androgen Receptor Expression in Early Triple-Negative Breast Cancer: Clinical Significance and Prognostic Associations

    International Nuclear Information System (INIS)

    Background: Triple-negative breast cancers (TNBC) are characterized by aggressive tumour biology resulting in a poor prognosis. Androgen receptor (AR) is one of newly emerging biomarker in TNBC. In recent years, ARs have been demonstrated to play an important role in the genesis and in the development of breast cancer, although their prognostic role is still debated. In the present study, we explored the correlation of AR expression with clinical, pathological and molecular features and its impact on prognosis in early TNBC. Patients and Methods: ARs were considered positive in case of tumors with >10% nuclear-stained. Survival distribution was estimated by the Kaplan Meier method. The univariate and multivariate analyses were performed. The difference among variables were calculated by chi-square test. Results: 81 TNBC patients diagnosed between January 2006 and December 2011 were included in the analysis. Slides were stained immunohistochemically for estrogen and progesterone receptors, HER-2, Ki-67, ALDH1, e-cadherin and AR. Of the 81 TNBC samples, 18.8% showed positive immunostaining for AR, 23.5% and 44.4% of patients were negative for e-cadherin and ALDH1, respectively. Positive AR immunostaining was inversely correlated with a higher Ki-67 (p < 0.0001) and a lympho-vascular invasion (p = 0.01), but no other variables. Univariate survival analysis revealed that AR expression was not associated with disease-free survival (p = 0.72) or overall survival (p = 0.93). Conclusions: The expression of AR is associated with some biological features of TNBC, such as Ki-67 and lympho-vascular invasion; nevertheless the prognostic significance of AR was not documented in our analysis. However, since ARs are expressed in a significant number of TNBC, prospective studies in order to determine the biological mechanisms and their potential role as novel treatment target

  17. Prognostic Significance of Subtype Classification for Short- and Long-Term Survival in Breast Cancer: Survival Time Holds the Key

    OpenAIRE

    Ambs, Stefan

    2010-01-01

    Stefan Ambs provides a perspective on a recent research article by Paul Pharoah and colleagues that evaluated the prognostic significance of immunohistochemical subtype classification in early breast cancer.

  18. A Multiple Survival Screening algorithm (MSS) for identifying high-quality cancer prognostic markers

    OpenAIRE

    sprotocols

    2015-01-01

    We have developed a Multiple Survival Screening algorithm (MSS) for identifying high-quality cancer prognostic markers from the gene expression profiles of cancer samples. By applying the MSS algorithm to breast cancer samples, we have identified several marker sets which showed ~90% predicting accuracy across 8 independent breast cancer cohorts. We realized that the algorithm could be used for finding other biomarkers including drug response markers. We are describing the protocol with some ...

  19. The prognostic significance of extramural deposits and extracapsular lymph node invasion in colon cancer.

    LENUS (Irish Health Repository)

    Al Sahaf, Osama

    2011-08-01

    The status of resected lymph nodes in colon cancer determines prognosis and further treatment. The American Joint Committee on Cancer staging system has designated extramural nodules as nonnodal disease and classified them as extensions of the T category in the sixth edition and as site-specific tumor deposits in the seventh edition. Extracapsular lymph node extension is an established poor prognostic indicator in many cancers. Its significance in colon cancer has not been extensively investigated.

  20. Prognostic Impact of ABO Blood Group on the Survival in Patients with Ovarian Cancer

    OpenAIRE

    Zhou, Juan; Yang, Li-Chao; He, Zhen-Yu; Li, Fang-Yan; Wu, San-Gang; Sun, Jia-yuan

    2015-01-01

    Purpose: The impact of ABO blood group on the survival of patients with ovarian cancer remains uncertain. The aim of this study was to evaluate the prognostic value of the ABO blood group in ovarian cancer patients. Methods: 256 ovarian cancer patients who received a cytoreductive surgery were retrospectively reviewed. The prognostic impact of the ABO blood group with respect to overall survival (OS) was analyzed. Results: The median follow-up time was 57 months and the 5-year OS was 70.1%. T...

  1. Ovarian Cancer Stroma: Pathophysiology and the Roles in Cancer Development

    International Nuclear Information System (INIS)

    Ovarian cancer represents one of the cancers with the worst prognostic in adult women. More than half of the patients who present with clinical signs such as abdominal bloating and a feeling of fullness already show advanced stages. The majority of ovarian cancers grow as cystic masses, and cancer cells easily spread into the pelvic cavity once the cysts rupture or leak. When the ovarian cancer cells disseminate into the peritoneal cavity, metastatic nests may grow in the cul-de-sac, and in more advanced stages, the peritoneal surfaces of the upper abdomen become the next largest soil for cancer progression. Ascites is also produced frequently in ovarian cancers, which facilitates distant metastasis. Clinicopathologic, epidemiologic and molecular studies on ovarian cancers have improved our understanding and therapeutic approaches, but still further efforts are required to reduce the risks in the patients who are predisposed to this lethal disease and the mortality of the patients in advanced stages. Among various molecules involved in ovarian carcinogenesis, special genes such as TP53, BRCA1 and BRCA2 have been well investigated. These genes are widely accepted as the predisposing factors that trigger malignant transformation of the epithelial cells of the ovary. In addition, adnexal inflammatory conditions such as chronic salpingitis and ovarian endometriosis have been great research interests in the context of carcinogenic background of ovarian cancers. In this review, I discuss the roles of stromal cells and inflammatory factors in the carcinogenesis and progression of ovarian cancers

  2. Ovarian Cancer Stroma: Pathophysiology and the Roles in Cancer Development

    Energy Technology Data Exchange (ETDEWEB)

    Furuya, Mitsuko [Department of Pathology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004 (Japan)

    2012-07-18

    Ovarian cancer represents one of the cancers with the worst prognostic in adult women. More than half of the patients who present with clinical signs such as abdominal bloating and a feeling of fullness already show advanced stages. The majority of ovarian cancers grow as cystic masses, and cancer cells easily spread into the pelvic cavity once the cysts rupture or leak. When the ovarian cancer cells disseminate into the peritoneal cavity, metastatic nests may grow in the cul-de-sac, and in more advanced stages, the peritoneal surfaces of the upper abdomen become the next largest soil for cancer progression. Ascites is also produced frequently in ovarian cancers, which facilitates distant metastasis. Clinicopathologic, epidemiologic and molecular studies on ovarian cancers have improved our understanding and therapeutic approaches, but still further efforts are required to reduce the risks in the patients who are predisposed to this lethal disease and the mortality of the patients in advanced stages. Among various molecules involved in ovarian carcinogenesis, special genes such as TP53, BRCA1 and BRCA2 have been well investigated. These genes are widely accepted as the predisposing factors that trigger malignant transformation of the epithelial cells of the ovary. In addition, adnexal inflammatory conditions such as chronic salpingitis and ovarian endometriosis have been great research interests in the context of carcinogenic background of ovarian cancers. In this review, I discuss the roles of stromal cells and inflammatory factors in the carcinogenesis and progression of ovarian cancers.

  3. Building prognostic models for breast cancer patients using clinical variables and hundreds of gene expression signatures

    Directory of Open Access Journals (Sweden)

    Liu Yufeng

    2011-01-01

    Full Text Available Abstract Background Multiple breast cancer gene expression profiles have been developed that appear to provide similar abilities to predict outcome and may outperform clinical-pathologic criteria; however, the extent to which seemingly disparate profiles provide additive prognostic information is not known, nor do we know whether prognostic profiles perform equally across clinically defined breast cancer subtypes. We evaluated whether combining the prognostic powers of standard breast cancer clinical variables with a large set of gene expression signatures could improve on our ability to predict patient outcomes. Methods Using clinical-pathological variables and a collection of 323 gene expression "modules", including 115 previously published signatures, we build multivariate Cox proportional hazards models using a dataset of 550 node-negative systemically untreated breast cancer patients. Models predictive of pathological complete response (pCR to neoadjuvant chemotherapy were also built using this approach. Results We identified statistically significant prognostic models for relapse-free survival (RFS at 7 years for the entire population, and for the subgroups of patients with ER-positive, or Luminal tumors. Furthermore, we found that combined models that included both clinical and genomic parameters improved prognostication compared with models with either clinical or genomic variables alone. Finally, we were able to build statistically significant combined models for pathological complete response (pCR predictions for the entire population. Conclusions Integration of gene expression signatures and clinical-pathological factors is an improved method over either variable type alone. Highly prognostic models could be created when using all patients, and for the subset of patients with lymph node-negative and ER-positive breast cancers. Other variables beyond gene expression and clinical-pathological variables, like gene mutation status or DNA

  4. EVALUATION OF THE PROGNOSTIC VALUE OF nm23 GENE EXPRESSION IN BREAST CANCER

    Institute of Scientific and Technical Information of China (English)

    刘红; 毛慧生; 傅西林; 方志沂; 冯玉梅; 范宇; 李树玲

    2002-01-01

    Objective: To investigate the expression of nm23 gene and evaluate its prognostic value in breast cancer. Methods: nm23 expressions were detected in 101 breast cancer patients (group 1) by immunohistochemistry. RT-PCR and immunohistochemistry were used to measure expressions of nm23 gene in another 68 patients with breast cancer (group 2). Results: nm23 gene expression in group 1 was inversely associated with distant metastasis and lymph node metastasis (P<0.05). In 44 patients with negative lymph node, 9 cases progressed to distant metastasis, 7 of them (77.8%) showed low expression of nm23 gene (P<0.05). In 57 patients with positive lymph node, 24 our of 29 patients who had no distant metastasis (82.8%) expressed nm23 gene at high level (P<0.05). Meanwhile, there were 6 patients with distant metastasis in the group 2, all of thenm expressed nm23 gene mRNA at low level. Conclusion: The results showed that nm23 gene might play an independent role in predicting prognosis of breast cancer.

  5. The prognostic significance of specific HOX gene expression patterns in ovarian cancer.

    Science.gov (United States)

    Kelly, Zoe; Moller-Levet, Carla; McGrath, Sophie; Butler-Manuel, Simon; Kavitha Madhuri, Thumuluru; Kierzek, Andrzej M; Pandha, Hardev; Morgan, Richard; Michael, Agnieszka

    2016-10-01

    HOX genes are vital for all aspects of mammalian growth and differentiation, and their dysregulated expression is related to ovarian carcinogenesis. The aim of the current study was to establish the prognostic value of HOX dysregulation as well as its role in platinum resistance. The potential to target HOX proteins through the HOX/PBX interaction was also explored in the context of platinum resistance. HOX gene expression was determined in ovarian cancer cell lines and primary EOCs by QPCR, and compared to expression in normal ovarian epithelium and fallopian tube tissue samples. Statistical analysis included one-way ANOVA and t-tests, using statistical software R and GraphPad. The analysis identified 36 of the 39 HOX genes as being overexpressed in high grade serous EOC compared to normal tissue. We detected a molecular HOX gene-signature that predicted poor outcome. Overexpression of HOXB4 and HOXB9 was identified in high grade serous cell lines after platinum resistance developed. Targeting the HOX/PBX dimer with the HXR9 peptide enhanced the cytotoxicity of cisplatin in platinum-resistant ovarian cancer. In conclusion, this study has shown the HOX genes are highly dysregulated in ovarian cancer with high expression of HOXA13, B6, C13, D1 and D13 being predictive of poor clinical outcome. Targeting the HOX/PBX dimer in platinum-resistant cancer represents a potentially new therapeutic option that should be further developed and tested in clinical trials. PMID:27225067

  6. Circulating Tumor Cells in Metastatic Breast Cancer: A Prognostic and Predictive Marker

    Directory of Open Access Journals (Sweden)

    Sayyed Farshid Moussavi-Harami

    2014-05-01

    Full Text Available The role of circulating tumor cells (CTCs as a marker for disease progression in metastatic cancer is controversial. The current review will serve to summarize the evidence on CTCs as a marker of disease progression in patients with metastatic breast cancer. The immunohistochemistry (IHC-based CellSearch® is the only FDA-approved isolation technique for quantifying CTCs in patients with metastatic breast cancer. We searched PubMed and Web of Knowledge for clinical studies that assessed the prognostic and predictive value of CTCs using IHC-based isolation. The patient outcomes reported include median and Cox-proportional hazard ratios for overall survival (OS and progression-free survival (PFS. All studies reported shorter OS for CTC-positive patients versus CTC-negative. A subset of the selected trials reported significant lower median PFS for CTC-positive patients. The reported trials support the utility of CTC enumeration for patient prognosis. But further studies are required to determine the utility of CTC enumeration for guiding patient therapy. There are three clinical trials ongoing to test this hypothesis. These studies, and others, will further establish the role of CTCs in clinical practice.

  7. Context-dependent interpretation of the prognostic value of BRAF and KRAS mutations in colorectal cancer

    International Nuclear Information System (INIS)

    The mutation status of the BRAF and KRAS genes has been proposed as prognostic biomarker in colorectal cancer. Of them, only the BRAF V600E mutation has been validated independently as prognostic for overall survival and survival after relapse, while the prognostic value of KRAS mutation is still unclear. We investigated the prognostic value of BRAF and KRAS mutations in various contexts defined by stratifications of the patient population. We retrospectively analyzed a cohort of patients with stage II and III colorectal cancer from the PETACC-3 clinical trial (N = 1,423), by assessing the prognostic value of the BRAF and KRAS mutations in subpopulations defined by all possible combinations of the following clinico-pathological variables: T stage, N stage, tumor site, tumor grade and microsatellite instability status. In each such subpopulation, the prognostic value was assessed by log rank test for three endpoints: overall survival, relapse-free survival, and survival after relapse. The significance level was set to 0.01 for Bonferroni-adjusted p-values, and a second threshold for a trend towards statistical significance was set at 0.05 for unadjusted p-values. The significance of the interactions was tested by Wald test, with significance level of 0.05. In stage II-III colorectal cancer, BRAF mutation was confirmed a marker of poor survival only in subpopulations involving microsatellite stable and left-sided tumors, with higher effects than in the whole population. There was no evidence for prognostic value in microsatellite instable or right-sided tumor groups. We found that BRAF was also prognostic for relapse-free survival in some subpopulations. We found no evidence that KRAS mutations had prognostic value, although a trend was observed in some stratifications. We also show evidence of heterogeneity in survival of patients with BRAF V600E mutation. The BRAF mutation represents an additional risk factor only in some subpopulations of colorectal cancers, in

  8. Pretreatment serum albumin: a prognostic indicator of survival in oral cancer

    Directory of Open Access Journals (Sweden)

    Saurabh Bobdey

    2016-06-01

    Conclusion: Pretreatment serum albumin levels are of useful prognostic significance in oral cancer patients. Thus, this easily accessible variable may not only serve as a potent marker to predict the outcomes, but more importantly as an indicator for initiating aggressive nutrition intervention in oral cancer patients. [Int J Res Med Sci 2016; 4(6.000: 2135-2141

  9. High myeloperoxidase positive cell infiltration in colorectal cancer is an independent favorable prognostic factor.

    Directory of Open Access Journals (Sweden)

    Raoul A Droeser

    Full Text Available BACKGROUND: Colorectal cancer (CRC infiltration by adaptive immune system cells correlates with favorable prognosis. The role of the innate immune system is still debated. Here we addressed the prognostic impact of CRC infiltration by neutrophil granulocytes (NG. METHODS: A TMA including healthy mucosa and clinically annotated CRC specimens (n = 1491 was stained with MPO and CD15 specific antibodies. MPO+ and CD15+ positive immune cells were counted by three independent observers. Phenotypic profiles of CRC infiltrating MPO+ and CD15+ cells were validated by flow cytometry on cell suspensions derived from enzymatically digested surgical specimens. Survival analysis was performed by splitting randomized data in training and validation subsets. RESULTS: MPO+ and CD15+ cell infiltration were significantly correlated (p<0.0001; r = 0.76. However, only high density of MPO+ cell infiltration was associated with significantly improved survival in training (P = 0.038 and validation (P = 0.002 sets. In multivariate analysis including T and N stage, vascular invasion, tumor border configuration and microsatellite instability status, MPO+ cell infiltration proved an independent prognostic marker overall (P = 0.004; HR = 0.65; CI:±0.15 and in both training (P = 0.048 and validation (P = 0.036 sets. Flow-cytometry analysis of CRC cell suspensions derived from clinical specimens showed that while MPO+ cells were largely CD15+/CD66b+, sizeable percentages of CD15+ and CD66b+ cells were MPO-. CONCLUSIONS: High density MPO+ cell infiltration is a novel independent favorable prognostic factor in CRC.

  10. Circulating Fibroblast Growth Factor 21 (Fgf21) as Diagnostic and Prognostic Biomarker in Renal Cancer

    Science.gov (United States)

    Knott, ME; Minatta, JN; Roulet, L; Gueglio, G; Pasik, L; Ranuncolo, SM; Nuñez, M; Puricelli, L; De Lorenzo, MS

    2016-01-01

    Background The finding of new biomarkers is needed to have a better sub-classification of primary renal tumors (RCC) as well as more reliable predictors of outcome and therapy response. In this study, we evaluated the role of circulating FGF21, an endocrine factor, as a diagnostic and prognostic biomarker for ccRCC. Materials and Methods Serum samples from healthy controls (HC), clear cell and chromophobe RCC cancer patients were obtained from the serum biobank “Biobanco Público de Muestras Séricas Oncológicas” (BPMSO) of the “Instituto de Oncología “Ángel H. Roffo”. Serum FGF21 and leptin were measured by ELISA while other metabolic markers were measured following routinely clinical procedures. Results One of our major findings was that FGF21 levels were significantly increased in ccRCC patients compared with HC. Moreover, we showed an association between the increased serum FGF21 levels and the shorter disease free survival in a cohort of 98 ccRCC patients, after adjustment for other predictors of outcome. Conclusion Our results suggest that higher FGF21 serum level is an independent prognostic biomarker, associated with worse free-disease survival. PMID:27358750

  11. Prognostic value of the Glasgow Prognostic Score in metastatic colorectal cancer in the era of anti-EGFR therapies.

    Science.gov (United States)

    Dréanic, Johann; Maillet, Marianne; Dhooge, Marion; Mir, Olivier; Brezault, Catherine; Goldwasser, François; Chaussade, Stanislas; Coriat, Romain

    2013-01-01

    The Glasgow Prognostic Score (GPS), combination of C-reactive protein and albumin, has proven its prognostic value in metastatic colorectal cancer (mCRC) patients receiving conventional cytotoxic therapy. More recently, anti-EGFR therapies have been validated in mCRC and roll forward the patients' overall survival (OS). We aimed to evaluate the prognostic accuracy of the GPS in patients receiving anti-EGFR therapy in addition to conventional chemotherapy. From January 2007 to February 2012, consecutive mCRC patients who received 5-fluorouracil-based chemotherapy plus cetuximab were included in the present analysis. Patients were eligible for the study if they met the following criteria: advanced pathologically proven MCRC, age >18 years, adequate renal function (creatinine clearance >40 ml/min), C-reactive protein and albumin and performance status evaluation before treatment initiation. A total of 49 patients received cetuximab plus 5-fluorouracil-based chemotherapy (colon, n = 34; rectum, n = 15) and were treated with a median follow-up of 35 months (16.5-74.7). Median age was 48 years old. In addition to cetuximab, patients received oxaliplatin- (n = 34, 60%) or irinotecan (n = 15, 30%)-based chemotherapy. At time of diagnosis, 55, 29 and 16% of patients had a GPS of 0 (n = 27), 1 (n = 14) and 2 (n = 8), respectively. Fifty-five, 29 and 14 % of patients add one, two or ≥3 metastatic sites, respectively. Considering two groups (GPS = 0 and GPS ≥1), median progression-free survivals were significantly different (p = 0.0084). Median OS in the GPS 0, 1 and 2 groups were 38.2, 14 and 12.1 months, respectively (p = 0.0093). The results of the present study confirm that the GPS is still a simple and effective prognostic factor in the era of cetuximab therapy in mCRC patients. PMID:23839775

  12. Impacts of Exercise on Prognostic Biomarkers in Lung Cancer Patients

    Science.gov (United States)

    2016-02-18

    Extensive Stage Small Cell Lung Cancer; Healthy, no Evidence of Disease; Limited Stage Small Cell Lung Cancer; Recurrent Non-small Cell Lung Cancer; Recurrent Small Cell Lung Cancer; Stage IA Non-small Cell Lung Cancer; Stage IB Non-small Cell Lung Cancer; Stage IIA Non-small Cell Lung Cancer; Stage IIB Non-small Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer

  13. Comorbidity is an independent prognostic factor in women with uterine corpus cancer

    DEFF Research Database (Denmark)

    Noer, Mette C; Sperling, Cecilie; Christensen, Ib J;

    2014-01-01

    OBJECTIVE: To determine whether comorbidity independently affects overall survival in women with uterine corpus cancer. DESIGN: Cohort study. SETTING: Denmark. STUDY POPULATION: A total of 4244 patients registered in the Danish Gynecologic Cancer database with uterine corpus cancer from 1 January...... status might capture the prognostic impact of comorbidity and because information on the variable grade was missing in some special histological subtypes, we included different models in the multivariate analyses with and without PS and grade, respectively. MAIN OUTCOME MEASURES: Overall survival....... RESULTS: Univariate survival analysis showed a significant (p < 0.001) negative association between increasing level of comorbidity and overall survival. Multivariate analyses adjusting for other prognostic factors showed that comorbidity is a significant independent prognostic factor with hazard ratios...

  14. Short-Term Prognostic Index for Breast Cancer: NPI or Lpi

    Directory of Open Access Journals (Sweden)

    V. Van Belle

    2011-01-01

    Full Text Available Axillary lymph node involvement is an important prognostic factor for breast cancer survival but is confounded by the number of nodes examined. We compare the performance of the log odds prognostic index (Lpi, using a ratio of the positive versus negative lymph nodes, with the Nottingham Prognostic Index (NPI for short-term breast cancer specific disease free survival. A total of 1818 operable breast cancer patients treated in the University Hospital of Leuven between 2000 and 2005 were included. The performance of the NPI and Lpi were compared on two levels: calibration and discrimination. The latter was evaluated using the concordance index (cindex, the number of patients in the extreme groups, and difference in event rates between these. The NPI had a significant higher cindex, but a significant lower percentage of patients in the extreme risk groups. After updating both indices, no significant differences between NPI and Lpi were noted.

  15. Skeletal Muscle Depletion and Markers for Cancer Cachexia Are Strong Prognostic Factors in Epithelial Ovarian Cancer.

    Directory of Open Access Journals (Sweden)

    Stefanie Aust

    Full Text Available Tumor cachexia is an important prognostic parameter in epithelial ovarian cancer (EOC. Tumor cachexia is characterized by metabolic and inflammatory disturbances. These conditions might be reflected by body composition measurements (BCMs ascertained by pre-operative computed tomography (CT. Thus, we aimed to identify the prognostically most relevant BCMs assessed by pre-operative CT in EOC patients.We evaluated muscle BCMs and well established markers of nutritional and inflammatory status, as well as clinical-pathological parameters in 140 consecutive patients with EOC. Furthermore, a multiplexed inflammatory marker panel of 25 cytokines was used to determine the relationship of BCMs with inflammatory markers and patient's outcome. All relevant parameters were evaluated in uni- and multivariate survival analysis.Muscle attenuation (MA-a well established BCM parameter-is an independent prognostic factor for survival in multivariate analysis (HR 2.25; p = 0.028. Low MA-reflecting a state of cachexia-is also associated with residual tumor after cytoreductive surgery (p = 0.046 and with an unfavorable performance status (p = 0.015. Moreover, MA is associated with Eotaxin and IL-10 out of the 25 cytokine multiplex marker panel in multivariate linear regression analysis (p = 0.021 and p = 0.047, respectively.MA-ascertained by routine pre-operative CT-is an independent prognostic parameter in EOC patients. Low MA is associated with the inflammatory, as well as the nutritional component of cachexia. Therefore, the clinical value of pre-operative CT could be enhanced by the assessment of MA.

  16. Prognostic value of lymph node ratio in node-positive breast cancer in Egyptian patients

    International Nuclear Information System (INIS)

    Background: Breast cancer in Egypt is the most common cancer among women and is the leading cause of cancer mortality. Traditionally, axillary lymph node involvement is considered among the most important prognostic factors in breast cancer. Nonetheless, accumulating evidence suggests that axillary lymph node ratio should be considered as an alternative to classical pN classification. Materials and methods: We performed a retrospective analysis of patients with operable node positive breast cancer, to investigate the prognostic significance of axillary lymph node ratio. Results: Five-hundred patients were considered eligible for the analysis. Median follow-up was 35 months (95% Cl 32-37 months), the median disease-free survival (DFS) was 49 months (95% Cl, 46.4-52.2 months). The classification of patients based on pN staging system failed to prognosticate DFS in the multivariate analysis. Conversely, grade 3 tumors, and the intermediate (> 0.20 to <0.65) and high (>0.65) LNR were the only variables that were independently associated with adverse DFS. The overall survival (OS) in this series was 69 months (95% Cl 60-77). Conclusion: The analysis of outcome of patients with early breast cancer in Egypt identified the adverse prognostic effects of high tumor grade, ER negativity and intermediate and high LNR on DFS. If the utility of the LNR is validated in other studies, it may replace the use of absolute number of axillary lymph nodes.

  17. Prognostic Impact of Vitamin B6 Metabolism in Lung Cancer

    Directory of Open Access Journals (Sweden)

    Lorenzo Galluzzi

    2012-08-01

    Full Text Available Patients with non-small cell lung cancer (NSCLC are routinely treated with cytotoxic agents such as cisplatin. Through a genome-wide siRNA-based screen, we identified vitamin B6 metabolism as a central regulator of cisplatin responses in vitro and in vivo. By aggravating a bioenergetic catastrophe that involves the depletion of intracellular glutathione, vitamin B6 exacerbates cisplatin-mediated DNA damage, thus sensitizing a large panel of cancer cell lines to apoptosis. Moreover, vitamin B6 sensitizes cancer cells to apoptosis induction by distinct types of physical and chemical stress, including multiple chemotherapeutics. This effect requires pyridoxal kinase (PDXK, the enzyme that generates the bioactive form of vitamin B6. In line with a general role of vitamin B6 in stress responses, low PDXK expression levels were found to be associated with poor disease outcome in two independent cohorts of patients with NSCLC. These results indicate that PDXK expression levels constitute a biomarker for risk stratification among patients with NSCLC.

  18. The strong prognostic value of KELIM, a model-based parameter from CA 125 kinetics in ovarian cancer

    DEFF Research Database (Denmark)

    You, Benoit; Colomban, Olivier; Heywood, Mark; Lee, Chee; Davy, Margaret; Reed, Nicholas; Pignata, Sandro; Varsellona, Nenzi; Emons, Günter; Rehman, Khalid; Steffensen, Karina Dahl; Reinthaller, Alexander; Pujade-Lauraine, Eric; Oza, Amit

    2013-01-01

    Unexpected results were recently reported about the poor surrogacy of Gynecologic Cancer Intergroup (GCIG) defined CA-125 response in recurrent ovarian cancer (ROC) patients. Mathematical modeling may help describe CA-125 decline dynamically and discriminate prognostic kinetic parameters....

  19. Hypoxia-inducible factor 1 alpha in high-risk breast cancer: an independent prognostic parameter?

    International Nuclear Information System (INIS)

    Hypoxia-inducible factor 1 alpha (hif-1α) furnishes tumor cells with the means of adapting to stress parameters like tumor hypoxia and promotes critical steps in tumor progression and aggressiveness. We investigated the role of hif-1α expression in patients with node-positive breast cancer. Tumor samples from 77 patients were available for immunohistochemistry. The impact of hif-1α immunoreactivity on survival endpoints was determined by univariate and multivariate analyses, and correlations to clinicopathological characteristics were determined by cross-tabulations. hif-1α was expressed in 56% (n = 43/77) of the patients. Its expression correlated with progesterone receptor negativity (P = 0.002). The Kaplan–Meier curves revealed significantly shorter distant metastasis-free survival (DMFS) (P = 0.04, log-rank) and disease-free survival (DFS) (P = 0.04, log-rank) in patients with increased hif-1α expression. The difference in overall survival (OS) did not attain statistical significance (5-year OS, 66% without hif-1α expression and 55% with hif-1α expression; P = 0.21). The multivariate analysis failed to reveal an independent prognostic value for hif-1α expression in the whole patient group. The only significant parameter for all endpoints was the T stage (T3/T4 versus T1/T2: DMFS, relative risk = 3.16, P = 0.01; DFS, relative risk = 2.57, P = 0.03; OS, relative risk = 3.03, P = 0.03). Restricting the univariate and multivariate analyses to T1/T2 tumors, hif-1α expression was a significant parameter for DFS and DMFS. hif-1α is expressed in the majority of patients with node-positive breast cancer. It can serve as a prognostic marker for an unfavorable outcome in those with T1/T2 tumors and positive axillary lymph nodes

  20. Nomograms for predicting prognostic value of inflammatory biomarkers in colorectal cancer patients after radical resection.

    Science.gov (United States)

    Li, Yaqi; Jia, Huixun; Yu, Wencheng; Xu, Ye; Li, Xinxiang; Li, Qingguo; Cai, Sanjun

    2016-07-01

    Increasing evidence indicates that inflammation plays a vital role in tumorigenesis and progression. However, the prognostic value of inflammatory biomarkers in colorectal cancer (CRC) has not been established. In this study, a retrospective analysis was conducted in patients with CRC in Fudan University Shanghai Cancer Center (FUSCC) between April 1, 2007 and April 30, 2014, and 5,336 patients were identified eligible. Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and albumin/globulin ratio (AGR) were analyzed. Kaplan-Meier analysis was used to calculate the 5-year overall survival (OS) and disease-free survival (DFS). Cox regression analysis was performed to assess the prognostic factors. Nomograms were established to predict OS and DFS, and Harrell's concordance index (c-index) was adopted to evaluate prediction accuracy. As results, the 5-year OS was 79.2% and the 5-year DFS was 56.0% in the cohort. Patients were stratified into 2 groups by NLR (≤2.72 and >2.72), PLR (≤219.00 and >219.00), LMR (≤2.83 and >2.83) and AGR ( 2.72, PLR > 219.00, LMR ≤ 2.83 and AGR nomograms on OS and DFS were established according to all significant factors, and c-indexes were 0.765 (95% CI: 0.744-0.785) and 0.735 (95% CI: 0.721-0.749), respectively. Nomograms based on OS and DFS can be recommended as practical models to evaluate prognosis for CRC patients. PMID:26933932

  1. Recurrent epithelial ovarian cancer: Validation and improvement of an established prognostic index

    DEFF Research Database (Denmark)

    Gronlund, B; Christensen, Ib Jarle; Bülow-Lehnsby, A L; Engelholm, S A; Hansen, H H; Høgdall, C

    2005-01-01

    OBJECTIVES: To validate and improve an established prognostic index in patients with recurrent ovarian cancer. METHODS: A Canadian three-covariate prognostic index (tumour grade at diagnosis, initial performance status, and time to relapse/primary progression (TRP)) was validated in a well...... difference in survival between the prognostic groups good and intermediate (P<0.0001), whereas there was no significant difference in survival between the prognostic groups intermediate and poor (P=0.51). In order to improve the accuracy of the index, the candidate parameters, treatment free interval (TFI......), CA125 level and performance status, at time of relapse/primary progression, were added, whereas the parameters, tumour grade, and initial performance status, from the Canadian index were excluded. As the correlation coefficient between TRP and TFI was very high (r=0.91), TRP was substituted with TFI...

  2. Epithelial-mesenchymal transition-associated miRNAs in ovarian carcinoma, with highlight on the miR-200 family: prognostic value and prospective role in ovarian cancer therapeutics.

    Science.gov (United States)

    Koutsaki, Maria; Spandidos, Demetrios A; Zaravinos, Apostolos

    2014-09-01

    MicroRNAs (miRNAs) are a family of short ribonucleic acids found to play a pivotal role in cancer pathogenesis. MiRNAs are crucial in cellular differentiation, growth, stress response, cell death and other fundamental cellular processes, and their involvement in ovarian cancer has been recently shown. They can repress the expression of important cancer-related genes and they can also function both as oncogenes and tumour suppressor genes. During epithelial-mesenchymal transition (EMT), epithelial cells lose their cell polarity and cell-cell adhesion and gain migratory and invasive properties. In the ovarian surface epithelium, EMT is considered the key regulator of the post-ovulatory repair process and it can be triggered by a range of environmental stimuli. The aberrant expression of the miR-200 family (miR-200a, miR-200b, miR-200c, miR-141 and miR-429) in ovarian carcinoma and its involvement in ovarian cancer initiation and progression has been well-demonstrated. The miR-200 family members seem to be strongly associated with a pathologic EMT and to have a metastasis suppressive role. MiRNA signatures can accurately distinguish ovarian cancer from the normal ovary and can be used as diagnostic tools to predict the clinical response to chemotherapy. Recent evidence suggests a growing list of new miRNAs (miR-187, miR-34a, miR-506, miRNA-138, miR-30c, miR-30d, miR-30e-3p, miR-370 and miR-106a, among others) that are also implicated in ovarian carcinoma-associated EMT, either enhancing or suppressing it. MiRNA-based gene therapy provides a prospective anti-tumour approach for integrated cancer therapy. The aim of nanotechnology-based delivery approach for miRNA therapy is to overcome challenges in miRNA delivery and to effectively encourage the reprogramming of miRNA networks in cancer cells, which may lead to a clinically translatable miRNA-based therapy to benefit ovarian cancer patients. PMID:24952258

  3. miR-200家族作为卵巢癌预后标志物的meta分析%Prognostic Role of miR-200 Family in Ovarian Cancer: a Meta-analysis

    Institute of Scientific and Technical Information of China (English)

    朱晓南; 宗利丽; 付文博; 郝双; 管雁丞; 张宸铭

    2015-01-01

    Objective:To systemically evaluate the relationship between miR-200 family and the prognosis of ovarian cancer.Methods:A computer-based retrieval of PubMed,EMBASE,Web of Science,CNKI and Wanfang Database was performed for correlative literature to aggregate the survival results from their establishment to September 2013.Relevant data were extracted from studies investigating the relationship between miR-200 family expression and survival in ovarian cancer patients.The data were analyzed with meta analysis using Stata v1 1.0 software.Results:Seven studies were identified,involving 577 cases with ovarian cancer.Meta-analysis results showed that,the combined hazard ratio (HR) for miR-200 family in ovarian cancer was 1.347 (95%CI:1.052,1.725).Subgroup ofmiR-200a,miR-200c and miR-141 subjects for survival were 1.091 (95%CI:0.718,1.659),1.285 (95%CI:0.765,2.161),and 1.122 (95% CI:1.043,1.208),respectively.The risk of miR-200 family,miR-141 for prognosis in ovarian cancer patients was significant (P =0.018,P =0.002)).Conclusions:miR-200 family may act as a prognostic biomarker.%目的:系统评价miR-200家族(miR-200a、miR-200b、miR-200c、miR-141、miR-429)的表达与卵巢癌预后之间的关系.方法:仔细检索搜索美国国立图书馆(PubMed),荷兰医学文摘(EMBASE)以及ISIWeb of Science、CNKI、万方等数据库,与miR-200家族相关的卵巢癌预后的文献.检索日期为数据库的建库时间至2013年9月20日.提取与miR-200家族相关卵巢癌预后的相应数据,应用Stata11.0软件进行Meta分析.结果:共有7篇研究符合入选标准,累积肿瘤组织577例.Meta分析显示,miR-200家族低表达组的合并优势比是高表达组的1.347倍(95%CI:1.052,1.725).miR-200a、miR-200c、miR-141的亚组分析结果分别为1.091(95%CI:0.718,1.659)、1.285(95%CI:0.765,2.161),1.122 (95% CI:1.043-1.208).miR-200家族、miR-141与卵巢癌的预后之间的关系有统计学意义(P=0.018,P=0.002).结论:miR-200家族

  4. Molecular correlates and prognostic significance of SATB1 expression in colorectal cancer

    Directory of Open Access Journals (Sweden)

    Nodin Björn

    2012-08-01

    Full Text Available Abstract Background Special AT-rich sequence-binding protein 1 (SATB1 is a global gene regulator that has been reported to confer malignant behavior and associate with poor prognosis in several cancer forms. SATB1 expression has been demonstrated to correlate with unfavourable tumour characteristics in rectal cancer, but its association with clinical outcome in colorectal cancer (CRC remains unclear. In this study, we examined the prognostic impact of SATB1 expression in CRC, and its association with important molecular characteristics; i.e. beta-catenin overexpression, microsatellite instability (MSI screening status, and SATB2 expression. Methods Immunohistochemical expression of SATB1 and beta-catenin was assessed in tissue microarrays with tumours from 529 incident CRC cases in the prospective population-based Malmö Diet and Cancer Study, previously analysed for SATB2 expression and MSI screening status. Spearmans Rho and Chi-Square tests were used to explore correlations between SATB1 expression, clinicopathological and investigative parameters. Kaplan Meier analysis and Cox proportional hazards modelling were used to explore the impact of SATB1 expression on cancer specific survival (CSS and overall survival (OS. Results SATB1 was expressed in 222 (42% CRC cases and negative, or sparsely expressed, in adjacent colorectal mucosa (n = 16. SATB1 expression was significantly associated with microsatellite stable tumours (p interaction = 0.011 for CSS and HR = 2.31; 95% CI 1.32-4.04; pinteraction = 0.015 for OS, remaining significant in multivariable analysis. Conclusions The results of this study demonstrate that SATB1 expression in CRC is significantly associated with beta-catenin overexpression, microsatellite stability and SATB2 expression. Furthermore, SATB1 expression is a factor of poor prognosis in SATB2 negative tumours. Altogether, these data indicate an important role for SATB1 in colorectal carcinogenesis and

  5. Genetic and Prognostic Differences of Non-small Cell Lung Cancer between Elderly Patients and Younger Counterparts

    OpenAIRE

    Suda, Kenichi; Tomizawa, Kenji; Mizuuchi, Hiroshi; Ito, Simon; Kitahara, Hirokazu; Shimamatsu, Shinichiro; Kohno, Mikihiro; Yoshida, Tsukihisa; Okamoto, Tatsuro; Maehara, Yoshihiko; Yatabe, Yasushi; Mitsudomi, Tetsuya

    2012-01-01

    Many elderly patients suffer from lung cancers, but it is not clear if their lung cancers differ from those of younger patients. In this study, we compared genetic and prognostic characteristics of lung cancers of patients aged ≥75 years with those of patients aged ≤ 64 years. In the genetic analysis, we explored 292 surgically treated non-squamous cell lung cancers with known mutational status of epidermal growth factor (EGFR) and anaplastic lymphoma kinase (ALK). In the prognostic analysis,...

  6. Urokinase plasminogen activator (uPA and plasminogen activator inhibitor type-1 (PAI-1 in breast cancer - correlation with traditional prognostic factors

    Directory of Open Access Journals (Sweden)

    Lampelj Maja

    2015-12-01

    Full Text Available Background. Urokinase plasminogen activator (uPA and plasminogen activator inhibitor type-1 (PAI-1 play a key role in tumour invasion and metastasis. High levels of both proteolytic enzymes are associated with poor prognosis in breast cancer patients. The purpose of this study was to evaluate the correlation between traditional prognostic factors and uPA and PAI-1 expression in primary tumour of breast cancer patients.

  7. Gene Expression Programs in Response to Hypoxia: Cell Type Specificity and Prognostic Significance in Human Cancers.

    Directory of Open Access Journals (Sweden)

    2006-01-01

    Full Text Available BACKGROUND: Inadequate oxygen (hypoxia triggers a multifaceted cellular response that has important roles in normal physiology and in many human diseases. A transcription factor, hypoxia-inducible factor (HIF, plays a central role in the hypoxia response; its activity is regulated by the oxygen-dependent degradation of the HIF-1alpha protein. Despite the ubiquity and importance of hypoxia responses, little is known about the variation in the global transcriptional response to hypoxia among different cell types or how this variation might relate to tissue- and cell-specific diseases. METHODS AND FINDINGS: We analyzed the temporal changes in global transcript levels in response to hypoxia in primary renal proximal tubule epithelial cells, breast epithelial cells, smooth muscle cells, and endothelial cells with DNA microarrays. The extent of the transcriptional response to hypoxia was greatest in the renal tubule cells. This heightened response was associated with a uniquely high level of HIF-1alpha RNA in renal cells, and it could be diminished by reducing HIF-1alpha expression via RNA interference. A gene-expression signature of the hypoxia response, derived from our studies of cultured mammary and renal tubular epithelial cells, showed coordinated variation in several human cancers, and was a strong predictor of clinical outcomes in breast and ovarian cancers. In an analysis of a large, published gene-expression dataset from breast cancers, we found that the prognostic information in the hypoxia signature was virtually independent of that provided by the previously reported wound signature and more predictive of outcomes than any of the clinical parameters in current use. CONCLUSIONS: The transcriptional response to hypoxia varies among human cells. Some of this variation is traceable to variation in expression of the HIF1A gene. A gene-expression signature of the cellular response to hypoxia is associated with a significantly poorer prognosis

  8. The value of prognostic factors for uterine cervical cancer patients treated with irradiation alone

    International Nuclear Information System (INIS)

    The aim of our study was to investigate and evaluate the prognostic value of and correlations between preclinical and clinical factors such as the stage of the disease, blood Hb level before treatment, size of cervix and lymph nodes evaluated by CT, age, dose of irradiation and duration of radiotherapy related to overall survival, disease-free survival, local control and metastases-free survival in cervical cancer patients receiving radiotherapy alone. 162 patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIA-IIIB cervical carcinoma treated with irradiation were analysed. Univariate and multivariate analyses using the Cox regression model were performed to determine statistical significance of some tumor-related factors. The Hb level before treatment showed significant influence on overall survival (p = 0.001), desease free survival (p = 0.040) and local control (p = 0.038). The lymph node status (>10 mm) assessed on CT had impact on overall survival (p = 0,030) and local control (p = 0,036). The dose at point A had impact on disease free survival (p = 0,028) and local control (p = 0,021) and the radiotherapy duration had showed significant influence on overall survival (p = 0,045), disease free survival (p = 0,006) and local control (p = 0,033). Anemia is a significant and independent prognostic factor of overall survival, disease-free survival and local control in cervical cancer patients treated with irradiation. The size of lymph nodes in CT is an independent prognostic factor for overall survival and local control in cervical cancer patients. The size of cervix uteri evaluated by CT has no prognostic significance in cervical cancer patients treated with radiotherapy. The prognostic value of FIGO stage of cervical cancer is influenced by other factors, analyzed in this study and is not an independent prognostic factor

  9. MicroRNA dysregulation as a prognostic biomarker in colorectal cancer

    International Nuclear Information System (INIS)

    Colorectal cancer (CRC) is one of the most potentially curable cancers, yet it remains the fourth most common overall cause of cancer death worldwide. The identification of robust molecular prognostic biomarkers can refine the conventional tumor–node–metastasis staging system, avoid understaging of tumor, and help pinpoint patients with early-stage CRC who may benefit from aggressive treatments. Recently, epigenetic studies have provided new molecular evidence to better categorize the CRC subtypes and predict clinical outcomes. In this review, we summarize recent findings concerning the prognostic potential of microRNAs (miRNAs) in CRC. We first discuss the prognostic value of three tissue miRNAs (miR-21-5p, miR-29-3p, miR-148-3p) that have been examined in multiple studies. We also summarize the dysregulation of miRNA processing machinery DICER in CRC and its association with risk for mortality. We also reviewe the potential application of miRNA-associated single-nucleotide polymorphisms as prognostic biomarkers for CRC, especially the miRNA-associated polymorphism in the KRAS gene. Last but not least, we discuss the microsatellite instability-related miRNA candidates. Among all these candidates, miR-21-5p is the most promising prognostic marker, yet further prospective validation studies are required before it can go into clinical usage

  10. Integral analysis of p53 and its value as prognostic factor in sporadic colon cancer

    International Nuclear Information System (INIS)

    p53 (encoded by TP53) is involved in DNA damage repair, cell cycle regulation, apoptosis, aging and cellular senescence. TP53 is mutated in around 50% of human cancers. Nevertheless, the consequences of p53 inactivation in colon cancer outcome remain unclear. Recently, a new role of p53 together with CSNK1A1 in colon cancer invasiveness has been described in mice. By combining data on different levels of p53 inactivation, we aimed to predict p53 functionality and to determine its effects on colon cancer outcome. Moreover, survival effects of CSNK1A1 together with p53 were also studied. Eighty-three formalin fixed paraffin embedded colon tumors were enriched for tumor cells using flow sorting, the extracted DNA was used in a custom SNP array to determine chr17p13-11 allelic state; p53 immunostaining, TP53 exons 5, 6, 7 and 8 mutations were determined in combination with mRNA expression analysis on frozen tissue. Patients with a predicted functional p53 had a better prognosis than patients with non functional p53 (Log Rank p=0.009). Expression of CSNK1A1 modified p53 survival effects. Patients with low CSNK1A1 expression and non-functional p53 had a very poor survival both in the univariate (Log Rank p<0.001) and in the multivariate survival analysis (HR=4.74 95% CI 1.45 – 15.3 p=0.009). The combination of mutational, genomic, protein and downstream transcriptional activity data predicted p53 functionality which is shown to have a prognostic effect on colon cancer patients. This effect was specifically modified by CSKN1A1 expression

  11. FDG PET in patients with esophageal cancer undergoing curative surgery: prognostic implications

    International Nuclear Information System (INIS)

    Objective: Pathologically measured tumor length and the number of pathology positive lymph nodes were suggested to be independent prognostic factors in esophageal cancer, although they were not included in the official staging system. We investigated whether the SUV of the primary tumor, the tumor length measured on PET image and the number of FDG PET positive nodes were independent prognostic predictors over other clinical variables in patients with esophageal cancer undergoing curative surgery. Methods: Sixty-nine patients with newly diagnosed esophageal cancer who underwent preoperative FDG PET and curative esophagectomy were included. The events for survival analysis were defined as recurrence or metastasis and cancer-related death. The disease-free and overall survival durations to last follow-up were recorded for each patient. The disease-free and overall survival rates of each variable were estimated by the Kaplan-Meier method. The Cox proportional hazards model was used to evaluate independent prognostic variables for multivariate survival analysis. Results: Using univariate survival analysis, presence of adjuvant therapy, pathological stage, the number of CT positive nodes (0 vs. 1 vs. 32), tumor length on PET (cut-off = 3 cm, 5 cm), and the number of PET positive nodes (0 vs. 1 vs. 2 vs. 33) were significant prognostic predictors for disease-free survival. However, only the number of PET positive nodes was an independent significant prognostic predictor for disease-free survival in multivariate analysis. In univariate survival analysis, gender, presence of adjuvant therapy, clinical and pathological stages, the number of CT positive nodes, maximum SUV of primary tumor (cut-off = 6.3, 13.7), tumor length on PET, and the number of PET positive nodes were significant prognostic predictors for overall survival. In contrast, clinical stage, pathological stage, tumor length by PET, and the number of PET positive nodes were independent significant prognostic

  12. The Prognostic Value of Circumferential Resection Margin Involvement in Patients with Extraperitoneal Rectal Cancer.

    Science.gov (United States)

    Shin, Dong Woo; Shin, Jin Yong; Oh, Sung Jin; Park, Jong Kwon; Yu, Hyeon; Ahn, Min Sung; Bae, Ki Beom; Hong, Kwan Hee; Ji, Yong Il

    2016-04-01

    The prognostic influence of circumferential resection margin (CRM) status in extraperitoneal rectal cancer probably differs from that of intraperitoneal rectal cancer because of its different anatomical and biological behaviors. However, previous reports have not provided the data focused on extraperitoneal rectal cancer. Therefore, the aim of this study was to examine the prognostic significance of the CRM status in patients with extraperitoneal rectal cancer. From January 2005 to December 2008, 248 patients were treated for extraperitoneal rectal cancer and enrolled in a prospectively collected database. Extraperitoneal rectal cancer was defined based on tumors located below the anterior peritoneal reflection, as determined intraoperatively by a surgeon. Cox model was used for multivariate analysis to examine risk factors of recurrence and mortality in the 248 patients, and multivariate logistic regression analysis was performed to identify predictors of recurrence and mortality in 135 patients with T3 rectal cancer. CRM involvement for extraperitoneal rectal cancer was present in 29 (11.7%) of the 248 patients, and was the identified predictor of local recurrence, overall recurrence, and death by multivariate Cox analysis. In the 135 patients with T3 cancer, CRM involvement was found to be associated with higher probability of local recurrence and mortality. In extraperitoneal rectal cancer, CRM involvement is an independent risk factor of recurrence and survival. Based on the results of the present study, it seems that CRM involvement in extraperitoneal rectal cancer is considered an indicator for (neo)adjuvant therapy rather than conventional TN status. PMID:27097629

  13. Prognostic values of aldehyde dehydrogenase 1 isoenzymes in ovarian cancer

    OpenAIRE

    Ma YM; Zhao S

    2016-01-01

    Yu-mei Ma,1 Shan Zhao2 1Department of Pathology, 2Department of Cancer Second Division, The Second Hospital of Hebei Medical University, Shijiazhuang City, People’s Republic of China Abstract: Aldehyde dehydrogenase 1 (ALDH1) activity has been used as a functional stem cell marker to isolate cancer stem cells in different cancer types, including ovarian cancer. However, which ALDH1’s isoenzymes are contributing to ALDH1 activity in ovarian cancer remains elusive. In addition, th...

  14. Molecular Markers with Predictive and Prognostic Relevance in Lung Cancer

    OpenAIRE

    Alphy Rose-James; TT, Sreelekha

    2012-01-01

    Lung cancer accounts for the majority of cancer-related deaths worldwide of which non-small-cell lung carcinoma alone takes a toll of around 85%. Platinum-based therapy is the stronghold for lung cancer at present. The discovery of various molecular alterations that underlie lung cancer has contributed to the development of specifically targeted therapies employing specific mutation inhibitors. Targeted chemotherapy based on molecular profiling has shown great promise in lung cancer treatment...

  15. Serum cathepsin H as a potential prognostic marker in patients with colorectal cancer

    DEFF Research Database (Denmark)

    Schweiger, A; Christensen, Ib Jarle; Nielsen, Hans Jørgen; Sørensen, Steen; Brunner, N; Kos, J

    2005-01-01

    Cathepsin H is a lysosomal cysteine protease that may participate in tumor progression. In order to evaluate its potential as a prognostic marker, its protein levels were measured by ELISA in preoperative sera from 324 patients with colorectal cancer. The level of cathepsin H was significantly...

  16. Comorbidity is an independent prognostic factor for the survival of ovarian cancer

    DEFF Research Database (Denmark)

    Sperling, Cecilie; Noer, Mette Calundann; Christensen, Ib Jarle; Nielsen, Marie Louise Shee; Lidegaard, Ojvind; Høgdall, Claus

    2013-01-01

    OBJECTIVE: The aim of the study was to examine whether comorbidity is an independent prognostic factor for 3129 women diagnosed with ovarian cancer from 2005 to 2011. As Performance status (PS) might capture the impact of comorbidity we addressed whether comorbidity can be explained by PS or whet...

  17. A subclass of HER1 ligands are prognostic markers for survival in bladder cancer patients

    DEFF Research Database (Denmark)

    Thøgersen, Helle-Merete Vissing; Sørensen, B S; Poulsen, S S;

    2001-01-01

    Members of the epidermal growth factor (EGF) family have been suggested as prognostic markers in patients with bladder cancer. Thus far, there has been no consensus on their usefulness. We report an analysis of six ligands and two receptors of which a subset correlate to tumor stage and survival....

  18. FDG-PET parameters as prognostic factor in esophageal cancer patients: a review

    NARCIS (Netherlands)

    J.M.T. Omloo; M. van Heijl; O.S. Hoekstra; M.I. van Berge Henegouwen; J.J.B. van Lanschot; G.W. Sloof

    2011-01-01

    (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) has been used extensively to explore whether FDG Uptake can be used to provide prognostic information for esophageal cancer patients. The aim of the present review is to evaluate the literature available to date concerning the potential

  19. An overview of prognostic factors for long-term survivors of breast cancer

    NARCIS (Netherlands)

    I. Soerjomataram (Isabelle); M.W.J. Louwman (Marieke); J.G. Ribot (Jacques); J.A. Roukema; J.W.W. Coebergh (Jan Willem)

    2008-01-01

    textabstractBackground: Numerous studies have examined prognostic factors for survival of breast cancer patients, but relatively few have dealt specifically with 10+-year survivors. Methods: A review of the PubMed database from 1995 to 2006 was undertaken with the following inclusion criteria: media

  20. The Prognostic Value of Haplotypes in the Vascular Endothelial Growth Factor A Gene in Colorectal Cancer

    International Nuclear Information System (INIS)

    New prognostic markers in patients with colorectal cancer (CRC) are a prerequisite for individualized treatment. Prognostic importance of single nucleotide polymorphisms (SNPs) in the vascular endothelial growth factor A (VEGF-A) gene has been proposed. The objective of the present study was to investigate the prognostic importance of haplotypes in the VEGF-A gene in patients with CRC. The study included 486 patients surgically resected for stage II and III CRC, divided into two independent cohorts. Three SNPs in the VEGF-A gene were analyzed by polymerase chain reaction. Haplotypes were estimated using the PHASE program. The prognostic influence was evaluated using Kaplan-Meir plots and log rank tests. Cox regression method was used to analyze the independent prognostic importance of different markers. All three SNPs were significantly related to survival. A haplotype combination, responsible for this effect, was present in approximately 30% of the patients and demonstrated a significant relationship with poor survival, and it remained an independent prognostic marker after multivariate analysis, hazard ratio 2.46 (95% confidence interval 1.49–4.06), p < 0.001. Validation was provided by consistent findings in a second and independent cohort. Haplotype combinations call for further investigation

  1. Prognostic factors for gallbladder cancer in the laparoscopy era

    OpenAIRE

    Lee, Hak Youn; Kim, Young Hoon; Jung, Ghap Joong; Roh, Young Hoon; Park, Si Young; Kang, Nam Uk; Yoon, Soon Hwa; Cho, Jin Han; Roh, Myung Hwan; Han, Sang Young; Lee, Sung Wook; Baek, Yang Hyun; Jeong, Jin Sook

    2012-01-01

    Purpose Hepatobiliary surgery has changed dramatically in recent decades with the advent of laparoscopic techniques. The aim of this retrospective study was to compare survival rates according to stages, adjusting for important prognostic factors. Methods A retrospective study of a 17-year period from January 1994 to April 2011 was carried out. The cases studied were divided into two time period cohorts, those treated in the first 9-years (n = 109) and those treated in the last 7-years (n = 1...

  2. Alterations of MicroRNAs in Solid Cancers and Their Prognostic Value

    International Nuclear Information System (INIS)

    MicroRNAs (miRNAs) are evolutionarily conserved, naturally abundant, small, regulatory non-coding RNAs that inhibit gene expression at the post-transcriptional level in a sequence-specific manner. Each miRNA represses the protein expression of several coding genes in a manner proportional to the sequence complementarity with the target transcripts. MicroRNAs play key regulatory roles in organismal development and homeostasis. They control fundamental biological processes, such as stem-cell regulation and cellular metabolism, proliferation, differentiation, stress resistance, and apoptosis. Differential miRNA expression is found in malignant tumors in comparison to normal tissue counterparts. This indicates that miRNA deregulation contributes to the initiation and progression of cancer. Currently, miRNA expression signatures are being rigorously investigated in various tumor types, with the aim of developing novel, efficient biomarkers that can improve clinical management of cancer patients. This review discusses deregulated miRNAs in solid tumors, and focuses on their emerging prognostic potential

  3. A Nomogram to Predict Prognostic Value of Red Cell Distribution Width in Patients with Esophageal Cancer

    Directory of Open Access Journals (Sweden)

    Gui-Ping Chen

    2015-01-01

    Full Text Available Objectives. The prognostic value of inflammatory index in esophageal cancer (EC was not established. In the present study, we initially used a nomogram to predict prognostic value of red cell distribution width (RDW in patients with esophageal squamous cell carcinoma (ESCC. Methods. A total of 277 ESCC patients were included in this retrospective study. Kaplan-Meier method was used to calculate the cancer-specific survival (CSS. A nomogram was established to predict the prognosis for CSS. Results. The mean value of RDW was 14.5 ± 2.3%. The patients were then divided into two groups: RDW ≥ 14.5% and RDW < 14.5%. Patients with RDW < 14.5% had a significantly better 5-year CSS than patients with RDW ≥ 14.5% (43.9% versus 23.3%, P < 0.001. RDW was an independent prognostic factor in patients with ESCC (P = 0.036. A nomogram could be more accurate for CSS. Harrell’s c-index for CSS prediction was 0.68. Conclusion. RDW was a potential prognostic biomarker in patients with ESCC. The nomogram based on CSS could be used as an accurately prognostic prediction for patients with ESCC.

  4. Serum nucleosomes during neoadjuvant chemotherapy in patients with cervical cancer. Predictive and prognostic significance

    Directory of Open Access Journals (Sweden)

    Cetina Lucely

    2005-06-01

    Full Text Available Abstract Background It has been shown that free DNA circulates in serum plasma of patients with cancer and that at least part is present in the form of oligo- and monucleosomes, a marker of cell death. Preliminary data has shown a good correlation between decrease of nucleosomes with response and prognosis. Here, we performed pre- and post-chemotherapy determinations of serum nucleosomes with an enzyme-linked immunosorbent assay (ELISA method in a group of patients with cervical cancer receiving neoadjuvant chemotherapy. Methods From December 2000 to June 2001, 41 patients with cervical cancer staged as FIGO stages IB2-IIIB received three 21-day courses of carboplatin and paclitaxel, both administered at day 1; then, patients underwent radical hysterectomy. Nucleosomes were measured the day before (baseline, at day seven of the first course and day seven of the third course of chemotherapy. Values of nucleosomes were analyzed with regard to pathologic response and to time to progression-free and overall survival. Results All patients completed chemotherapy, were evaluable for pathologic response, and had nucleosome levels determined. At a mean follow-up of 23 months (range, 7–26 months, projected progression time and overall survival were 80.3 and 80.4%, respectively. Mean differential values of nucleosomes were lower in the third course as compared with the first course (p >0.001. The decrease in the third course correlated with pathologic response (p = 0.041. Survival analysis showed a statistically significant, better progression-free and survival time in patients who showed lower levels at the third course (p = 0.0243 and p = 0.0260, respectively. Cox regression analysis demonstrated that nucleosome increase in the third course increased risk of death to 6.86 (95% confidence interval [CI 95%], 0.84–56.0. Conclusion Serum nucleosomes may have a predictive role for response and prognostic significance in patients with cervical cancer

  5. Prostate Cancer: Prognostic factors, markers of outcome and design of clinical trials

    OpenAIRE

    Collette, Lau

    2006-01-01

    textabstractPhase III clinical trials to assess the clinical benefit of new treatment options often require large patient numbers and long follow-up, in particular in diseases with a long natural history, such as prostate cancer. In this thesis, we argue that in order to improve the efficiency of phase III prostate cancer clinical trials, a thorough understanding of prognostic factors of outcome is needed, as well as an exploration of potential predictive factors that might affect treatment b...

  6. Prognostic Nomograms for Predicting Survival and Distant Metastases in Locally Advanced Rectal Cancers

    OpenAIRE

    Junjie Peng; Ying Ding; Shanshan Tu; Debing Shi; Liang Sun; Xinxiang Li; Hongbin Wu; Sanjun Cai

    2014-01-01

    Aim To develop prognostic nomograms for predicting outcomes in patients with locally advanced rectal cancers who do not receive preoperative treatment. Materials and Methods A total of 883 patients with stage II–III rectal cancers were retrospectively collected from a single institution. Survival analyses were performed to assess each variable for overall survival (OS), local recurrence (LR) and distant metastases (DM). Cox models were performed to develop a predictive model for each endpoint...

  7. Prognostic Impact of the Signet Ring Cell Type in Node-Negative Gastric Cancer

    OpenAIRE

    Pengfei Kong; Ruiyan Wu; Chenlu Yang; Qirong Geng; Jianjun Liu; Shangxiang Chen; Xuechao Liu; Minting Ye; Wenzhuo He; Qiong Yang; Liangping Xia; Dazhi Xu

    2016-01-01

    Little is known regarding the prognostic impact of the signet ring cell (SRC) histotype on negative lymph nodes (LNs) in gastric cancer (GC). In this study, we aimed to investigate the differences between SRC and non-SRC GC patients without LN metastasis. The medical records of patients with GC who underwent gastrectomy at Sun Yat-Sen University Cancer Centre from 1996 to 2012 were reviewed to analyse the clinicopathologic characteristics associated with survival. A total of 480 cases of GC p...

  8. Role of MGMT as biomarker in colorectal cancer

    OpenAIRE

    Inno, Alessandro; Fanetti, Giuseppe; Di Bartolomeo, Maria; Gori, Stefania; Maggi, Claudia; Cirillo, Massimo; Iacovelli, Roberto; Nichetti, Federico; Martinetti, Antonia; de Braud, Filippo; Bossi, Ilaria; Pietrantonio, Filippo

    2014-01-01

    O6-methylguanine DNA methyltransferase (MGMT) gene promoter methylation plays an important role in colorectal carcinogenesis, occurring in about 30%-40% of metastatic colorectal cancer. Its prognostic role has not been defined yet, but loss of expression of MGMT, which is secondary to gene promoter methylation, results in an interesting high response to alkylating agents such as dacarbazine and temozolomide. In a phase 2 study on heavily pre-treated patients with MGMT methylated metastatic co...

  9. Deregulation of p27 by oncogenic signaling and its prognostic significance in breast cancer

    International Nuclear Information System (INIS)

    p27 is a key regulator of progression from G1 to S phase. Although the gene encoding p27 is rarely mutated in human cancers, p27 is functionally inactivated in a majority of human cancers through accelerated p27 proteolysis, through sequestration by cyclin D–cyclin-dependent kinase complexes and by cytoplasmic mislocalization. Here we review mechanisms whereby oncogenic activation of receptor tyrosine kinase and Ras pathways lead to accelerated p27 proteolysis and p27 mislocalization in cancer cells. The prognostic significance of p27 in human breast cancer is also reviewed

  10. Prognostic predictors for non-small cell lung cancer patients with brain metastasis after radiotherapy

    Directory of Open Access Journals (Sweden)

    Qiuhong FAN

    2008-06-01

    Full Text Available Background and objective Brain metastasis (BM is often found in the patients with lung cancer. Radiotherapy is regular and effective means of therapy and it aims at palliating symptoms and prolonging survival time. However, now there are different viewpoints on protocols of radiotherapy and prognostic factors. A retrospective analysis is used to evaluate the results of treatment for 82 cases with brain metastasis from non-small cell lung cancer (NSCLC and explore the prognostic factors to establish a prognostic index (PI model. Methods From Feb.1995 to Oct. 2006, 82 patients irradiated for BM from NSCLC, with both complete medical charts and follow-up data available, were eligible for this retrospective analysis. A number of potential factors which might affect prognosis after irradiation were evaluated. The significance of prognostic variables in the survival resulted from both univariate analysis by Kaplan-Meier combining with log-rank test and multivariate Cox regression model. The prognostic index (PI was established based on Cox regression analysis and subgrouping values. Results The follow-up time was 1-120 months. For the entire cohort, the median survival from the start of radiation for BM was 10.5 months, and the actuarial overall survival rate was 50.8%, 23.7% and 5.1% at 0.5, 1 and 2 years respectively. Univariate analysis showed KPS, control of primary tumor, interval from the beginning of diagnostic to BM, extracranial systemic metastasis, counts of lymphocyte and solitary BM were predictors of prognosis. However, in the Cox multivariate analysis, only KPS, control of primary tumor, interval from the beginning of diagnostic to BM and solitary BM were significant prognostic factors. The prognostic index was established based on Cox regression analysis and 82 patients were stratified good, intermediate and poor prognostic sub-groups. The difference of survival rate among 3 subgroups is significant (P<0.001. Conclusion Radiotherapy is

  11. Prognostic Significance of Apoptosis Related Gene Family bcl-2 in Human Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    To study the prognostic effect of bcl-2 oncogene and its gene family members bax, bcl-x expression in breast cancer patients. Methods: expression of bcl-2, bax proteins in 91 human breast cancer tissue sections were studied by immunohistochemical method. Bcl-x1 mRNA expression in frozen tissues from 16 breast cancer patients were detected using Northern blot method. Results: bcl-2 protein positivity was found in 60/91 (65.9%) patients, and bax positivity 59/91 (64.8%). Bcl-2 and bax expression levels were associated with apoptotic index(AI), histological grade, axillary lymph node metastasis, postoperative local recurrence and metastasis. Bcl-2 expression was related to ER positivity. In univariate analysis for disease free survival (DFS), bcl-2 and bax protein levels, and Al were all found to have prognostic value. The result of Cox's model multivariate analysis showed that bcl-2 protein level was an independent prognostic factor. In 16 frozen breast cancer tissues, 8/16(50%) had higher level of bcl-x1 mRNA, which showed correlation with bcl-2 protein expression and axillary lymph node metastasis. Conclusion: The findings indicate that dysregulated expressions of bcl-2, bax and bcl-x1 apoptosis-related genes, suggestive of serious deregulation of apoptotic process, may contribute to the biologic aggressiveness of breast cancer. Bcl-2 protein is an independent indicator of prognosis in breast cancer patients.

  12. Prognostic significance of cyclin D1 expression in colorectal cancer: a meta-analysis of observational studies.

    Directory of Open Access Journals (Sweden)

    Yang Li

    Full Text Available OBJECTIVE: Cyclin D1 plays a vital role in cancer cell cycle progression and is overexpressed in many human cancers, including colorectal cancer (CRC. However, the prognostic value of cyclin D1 overexpression in colorectal cancer is conflicting and heterogeneous. We conducted a meta-analysis to more precisely evaluate its prognostic significance. METHODS: A comprehensive literature search for relevant studies published up to January 2014 was performed using PubMed, EMBASE, and ISI Web of Science. The pooled hazard ratio (HR with 95% confidence intervals (CI was used to estimate the effects. RESULTS: 22 studies with 4150 CRC patients were selected to evaluate the association between cyclin D1 and overall survival (OS, disease-free survival (DFS and clinicopathological parameters. In a random-effects model, the results showed that cyclin D1 overexpression in CRC was significantly associated with both poor OS (HR = 0.73, 95% CI: 0.63-0.85, P<0.001 and DFS (HR = 0.60, 95% CI: 0.44-0.82, P = 0.001. Additionally, cyclin D1 overexpression was significantly associated with more relative older patients (≥ 60 years (OR 0.62, 95% CI 0.44-0.89, P = 0.009, T3,4 tumor invasion (OR 0.70, 95% CI 0.57-0.85, P<0.001, N positive (OR 0.75, 95% CI 0.60-0.95, P = 0.016 and distant metastasis (OR 0.60, 95% CI 0.36-0.99, P = 0.047 of CRC. CONCLUSION: The meta-analysis results indicated that cyclin D1 is an unfavorable prognostic factor for CRC. Cyclin D1 overexpression might be associated with poor clinical outcome and some clinicopathological factors such as age, T category, N category and distant metastasis in CRC patients.

  13. Montreal prognostic score: estimating survival of patients with non-small cell lung cancer using clinical biomarkers

    OpenAIRE

    Gagnon, B.; Agulnik, J S; Gioulbasanis, I; Kasymjanova, G.; Morris, D.; Macdonald, N.

    2013-01-01

    Background: For evidence-based medical practice, well-defined risk scoring systems are essential to identify patients with a poor prognosis. The objective of this study was to develop a prognostic score, the Montreal prognostic score (MPS), to improve prognostication of patients with incurable non-small cell lung cancer (NSCLC) in everyday practice. Methods: A training cohort (TC) and a confirmatory cohort (CC) of newly diagnosed patients with NSCLC planning to receive chemotherapy were used ...

  14. Prognostic Markers in Pancreatic Cancer: the tumor and its environment

    NARCIS (Netherlands)

    J. van der Zee (Jill)

    2012-01-01

    textabstractIncidence Pancreatic cancer is not one of the most common types of cancer; however it is most certainly one of the most devastating types, ranking fourth in the list of cancer related deaths with a 5-year survival of only 6%. In 2010 there were an estimated 43.140 new cases whereas 36.80

  15. Prognostic role of serum cytokeratin 19 fragments in advanced non-small-cell lung cancer: association of marker changes after two chemotherapy cycles with different measures of clinical response and survival

    OpenAIRE

    Nisman, B.; Biran, H; Heching, N; Barak, V; Ramu, N; Nemirovsky, I; Peretz, T

    2007-01-01

    Prognostic implication of serum cytokeratin 19 fragments (CYFRA 21-1) was explored in 60 advanced NSCLC patients, whereas in 45 patients assessable for serological response a ⩾35% CYFRA 21-1 decline after two chemotherapy cycles was strongly associated with non-progression (NP), defined as a sum of objective response (OR)+stable disease (P

  16. Independent prognostic value of eosinophil and mast cell infiltration in colorectal cancer tissue

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen; Hansen, Ulla; Christensen, Ib Jarle;

    1999-01-01

    .0001), high age ( p=0.0003), and tumour location in the rectum predicted poor survival, while high counts of eosinophils ( p=0.006) and mast cells ( p=0.02) predicted good survival. Tumour-associated eosinophilia and mastocytosis appear to be independent prognostic variables in colorectal cancer. Future......Overall peritumoural inflammatory cell infiltration is a prognostic variable in solid tumours, but the survival-related impact of the individual cell types within the infiltrate has still not been fully evaluated and compared with the conventional disease classification. In the present study, the...

  17. Morphological prognostic factors in breast cancer. Hospital Conrado Benitez, 1998-2002

    International Nuclear Information System (INIS)

    Breast cancer is a major health problem in women. In Cuba, the adjusted incidence rate to world population in 2004 indicates that it is the leading cause in females, with a figure of 30.3. Establish the most important prognostic factors has been the subject of several studies with the purposes of stratifying patients according to risk groups and treatment schedules. The overall objective was to determine the influence on survival at 5 years of morphological prognostic factors, determined by histological techniques. (Author)

  18. The expression level of HJURP has an independent prognostic impact and predicts the sensitivity to radiotherapy in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Zhi; Huang, Ge; Sadanandam, Anguraj; Gu, Shenda; Lenburg, Marc E; Pai, Melody; Bayani, Nora; Blakely, Eleanor A; Gray, Joe W; Mao, Jian-Hua

    2010-06-25

    Introduction: HJURP (Holliday Junction Recognition Protein) is a newly discovered gene reported to function at centromeres and to interact with CENPA. However its role in tumor development remains largely unknown. The goal of this study was to investigate the clinical significance of HJURP in breast cancer and its correlation with radiotherapeutic outcome. Methods: We measured HJURP expression level in human breast cancer cell lines and primary breast cancers by Western blot and/or by Affymetrix Microarray; and determined its associations with clinical variables using standard statistical methods. Validation was performed with the use of published microarray data. We assessed cell growth and apoptosis of breast cancer cells after radiation using high-content image analysis. Results: HJURP was expressed at higher level in breast cancer than in normal breast tissue. HJURP mRNA levels were significantly associated with estrogen receptor (ER), progesterone receptor (PR), Scarff-Bloom-Richardson (SBR) grade, age and Ki67 proliferation indices, but not with pathologic stage, ERBB2, tumor size, or lymph node status. Higher HJURP mRNA levels significantly decreased disease-free and overall survival. HJURP mRNA levels predicted the prognosis better than Ki67 proliferation indices. In a multivariate Cox proportional-hazard regression, including clinical variables as covariates, HJURP mRNA levels remained an independent prognostic factor for disease-free and overall survival. In addition HJURP mRNA levels were an independent prognostic factor over molecular subtypes (normal like, luminal, Erbb2 and basal). Poor clinical outcomes among patients with high HJURP expression werevalidated in five additional breast cancer cohorts. Furthermore, the patients with high HJURP levels were much more sensitive to radiotherapy. In vitro studies in breast cancer cell lines showed that cells with high HJURP levels were more sensitive to radiation treatment and had a higher rate of apoptosis

  19. Comparison of thymidine phosphorylase expression and prognostic factors in gallbladder and bile duct cancer

    Directory of Open Access Journals (Sweden)

    You Young

    2010-10-01

    Full Text Available Abstract Background Biliary tract cancers have limitations in information about different location-related pathogenesis and clinico-pathological characteristics. The goal of this study was to investigate anatomical site-related similarities and differences in biliary tract cancers and to assess the expression and clinical significance of functional proteins such as p53, cyclin D1, survivin, thymidine phosphorylase, and ERCC1. Methods One hundred and sixty-one patients with biliary tract adenocarcinomas, who underwent curative or palliative surgery in a single institution between October 1994 and December 2003 were evaluated, retrospectively. The level of protein expression of p53, cyclin D1, survivin, thymidine phosphorylase, and ERCC1 was assessed by immunohistochemistry. Results With respect to clinico-pathological characteristics, gallbladder cancer was more frequent in women, and bile duct cancer was more common in men. Perineural invasion was more common in bile duct cancer. Recurrence as a distant metastasis was more common in gallbladder cancer. Immunohistochemical analysis revealed that thymidine phosphorylase expression was significantly higher in gallbladder cancer than in bile duct cancer. Positive thymidine phosphorylase and p53 staining were associated with an advanced stage. Differentiation, vascular invasion, perineural invasion, lymphatic invasion, lymph node metastasis, and TNM stage independently predicted poor prognosis in biliary tract cancer. These correlations were seen more clearly in gallbladder cancer. The immunohistochemical staining patterns of p53, cyclin D1, survivin, thymidine phosphorylase, and ERCC1 showed no prognostic significance in biliary tract cancers. Conclusions We concluded that gallbladder and bile duct cancers are considered to be separate diseases with different clinico-pathological characteristics and prognostic factors. In addition, we hypothesize that high expression of thymidine phosphorylase by

  20. Prognostic factors in a series of 504 breast cancer patients with metastatic spinal cord compression

    International Nuclear Information System (INIS)

    This study was performed to identify new significant prognostic factors in breast cancer patients irradiated for metastatic spinal cord compression (MSCC). The data of 504 patients with breast cancer patients with MSCC were retrospectively analyzed with respect to posttreatment motor function, local control of MSCC, and survival. The investigated potential prognostic factors included age, Eastern Cooperative Oncology Group (ECOG) performance score, number of involved vertebrae, other bone metastases, visceral metastases, pretreatment ambulatory status, interval from cancer diagnosis to radiotherapy of MSCC, time developing motor deficits before radiotherapy, and the radiation schedule. On multivariate analysis, better functional outcome was associated with ambulatory status prior to RT (estimate - 1.29, p < 0.001), no visceral metastases (estimate - 0.52, p = 0.020), and slower development of motor deficits (estimate + 2.47, p < 0.001). Improved local control was significantly associated with no other bone metastases (risk ratio (RR) 4.33, 95% confidence interval (CI) 1.36-14.02, p = 0.013) and no visceral metastases (RR 3.02, 95% CI 1.42-6.40, p = 0.005). Improved survival was significantly associated with involvement of only 1-2 vertebrae (RR 1.27, 95% CI 1.01-1.60, p = 0.044), ambulatory status before radiotherapy (RR 1.75, 95% CI 1.23-2.50, p = 0.002), no other bone metastases (RR 1.93, 95% CI 1.18-3.13, p = 0.009), no visceral metastases (RR 7.60, 95% CI 5.39-10.84, p < 0.001), and time developing motor deficits before radiotherapy (RR 1.55, 95% CI 1.30-1.86, p < 0.001). Several new independent prognostic factors were identified for treatment outcomes. These prognostic factors should be considered in future trials and may be used to develop prognostic scores for breast cancer patients with MSCC. (orig.)

  1. Clinical outcomes of adjuvant radiation therapy and prognostic factors in early stage uterine cervical cancer

    International Nuclear Information System (INIS)

    To evaluate the outcomes of adjuvant radiotherapy (RT) and to analyze prognostic factors of survival in the International Federation of Gynecology and Obstetrics (FIGO) IB-IIA uterine cervical cancer. We retrospectively reviewed the medical records of 148 patients with FIGO IB-IIA uterine cervical cancer who underwent surgery followed by adjuvant RT at the Yonsei Cancer Center between June 1997 and December 2011. Adjuvant radiotherapy was delivered to the whole pelvis or an extended field with or without brachytherapy. Among all patients, 57 (38.5%) received adjuvant chemotherapy either concurrently or sequentially. To analyze prognostic factors, we assessed clinicopathologic variables and metabolic parameters measured on preoperative 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). To evaluate the predictive performance of metabolic parameters, receiver operating characteristic curve analysis was used. Overall survival (OS) and disease-free survival (DFS) were analyzed by the Kaplan-Meier method. The median follow-up period was 63.2 months (range, 2.7 to 206.8 months). Locoregional recurrence alone occurred in 6 patients, while distant metastasis was present in 16 patients, including 2 patients with simultaneous regional failure. The 5-year and 10-year OSs were 87.0% and 85.4%, respectively. The 5-year and 10-year DFSs were 83.8% and 82.5%, respectively. In multivariate analysis, pathologic type and tumor size were shown to be significant prognostic factors associated with both DFS and OS. In subset analysis of 40 patients who underwent preoperative PET/CT, total lesion glycolysis was shown to be the most significant prognostic factor among the clinicopathologic variables and metabolic parameters for DFS. Our results demonstrated that adjuvant RT following hysterectomy effectively improves local control. From the subset analysis of preoperative PET/CT, we can consider that metabolic parameters may hold prognostic significance

  2. Clinical, pathological and molecular prognostic factors in prostate cancer decision-making process.

    Science.gov (United States)

    Pugliese, Dario; Palermo, Giuseppe; Totaro, Angelo; Bassi, Pier Francesco; Pinto, Francesco

    2016-03-01

    Prostate cancer is the most common urologic neoplasm and the second leading cause of cancer-related death among men in many developed countries. Given the highly heterogeneous behaviour of the disease, there is a great need for prognostic factors, in order to stratify the clinical risk and give the best treatment options to the patient. Clinical factors, such as prostate-specific antigen value and derivatives, and pathological factors, such as stage and Gleason grading, are well kown prognostic factors. Nomograms can provide useful prediction in each clinical sceario. The field of molecular biomarkers is briskly evolving towards personalized medicine. TMPRSS2-ERG fusion, deletion of PTEN ed and gene panels are some of the more extensively explored molecular features in prostate cancer outcome prediction. In the near future, circulating tumour cells, exosomes and microRNAs could give us further, not invasive important tools. PMID:26917215

  3. Circulating microRNAs as Prognostic and Predictive Biomarkers in Patients with Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Jakob Vasehus Schou

    2016-06-01

    Full Text Available MiRNAs are suggested as promising cancer biomarkers. They are stable and extractable from a variety of clinical tissue specimens (fresh frozen or formalin fixed paraffin embedded tissue and a variety of body fluids (e.g., blood, urine, saliva. However, there are several challenges that need to be solved, considering their potential as biomarkers in cancer, such as lack of consistency between biomarker panels in independent studies due to lack of standardized sample handling and processing, use of inconsistent normalization approaches, and differences in patients populations. Focusing on colorectal cancer (CRC, divergent results regarding circulating miRNAs as prognostic or predictive biomarkers are reported in the literature. In the present review, we summarize the current data on circulating miRNAs as prognostic/predictive biomarkers in patients with localized and metastatic CRC (mCRC.

  4. Expression of phosphatase regenerating liver 3 is an independent prognostic indicator for gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Ni Dai; Ai-Ping Lu; Cheng-Chao Shou; Ji-You Li

    2009-01-01

    AIM:To investigate the prognostic significance of phosphatase regenerating liver 3 (PRL-3) protein expression in gastric cancer. METHODS:PRL-3 expression in paraffin-embedded tumor specimens from 293 patients with gastric cancer was studied retrospectively by immunohistochemistry. Monoclonal antibody specifically against PRL-3, 3B6, was obtained with hybridoma technique. RESULTS:Positive PRL-3 expression was detected in 43.3% (127 of 293) of gastric cancer cases. High expression of PRL-3 was positively correlated with tumor size, depth of invasion, vascular/lymphatic invasion, lymph node metastasis, high TNM stage and tumor recurrence. Patients with positive PRL-3 expression had a significantly lower 5-year survival rate than those with negative expression (28.3% vs 51.9%, P < 0.0001). Patients who received curative surgery, and with positive PRL-3 expression had a significant shorter overall survival and disease-free disadvantage over patients with negative expression (hazard ratio of 16.7 and 16.6, respectively;P < 0.0001 for both). Multivariate analysis revealed that PRL-3 expression was an independent prognostic indicator for overall and disease-free survival of gastric cancer patients, particularly for survival in TNM stage Ⅲ patients. CONCLUSION:PRL-3 expression is a new independent prognostic indicator to predict the potential of recurrence and survival in patients with gastric cancer at the time of tumor resection.

  5. Expression of phosphatase regenerating liver 3 is an independent prognostic indicator for gastric cancer

    Directory of Open Access Journals (Sweden)

    Ni Dai, Ai-Ping Lu, Cheng-Chao Shou, Ji-You Li

    2009-03-01

    Full Text Available AIM: To investigate the prognostic significance of phosphatase regenerating liver 3 (PRL-3 protein expression in gastric cancer.METHODS: PRL-3 expression in paraffin-embedded tumor specimens from 293 patients with gastric cancer was studied retrospectively by immunohistochemistry. Monoclonal antibody specifically against PRL-3, 3B6, was obtained with hybridoma technique.RESULTS: Positive PRL-3 expression was detected in 43.3% (127 of 293 of gastric cancer cases. High expression of PRL-3 was positively correlated with tumor size, depth of invasion, vascular/lymphatic invasion, lymph node metastasis, high TNM stage and tumor recurrence. Patients with positive PRL-3 expression had a significantly lower 5-year survival rate than those with negative expression (28.3% vs 51.9%, P < 0.0001. Patients who received curative surgery, and with positive PRL-3 expression had a significant shorter overall survival and disease-free disadvantage over patients with negative expression (hazard ratio of 16.7 and 16.6, respectively; P < 0.0001 for both. Multivariate analysis revealed that PRL-3 expression was an independent prognostic indicator for overall and disease-free survival of gastric cancer patients, particularly for survival in TNM stage III patients.CONCLUSION: PRL-3 expression is a new independent prognostic indicator to predict the potential of recurrence and survival in patients with gastric cancer at the time of tumor resection.

  6. Stage II colorectal cancer: lack of prognostic model

    Directory of Open Access Journals (Sweden)

    Abdelbaset Buhmeida

    2007-01-01

    Full Text Available TO THE EDITOR: Colorectal cancer (CRC is one of the most common malignant tumors worldwide (Gatta et al. 1998 [1], Repetto et al. 2003 [2] with the disease incidence rising along with an advanced age (Wymenga et al. 2001 [3], Franceschi et al. 2001 [4]. The overall mortality from CRC is 60%, which represents the second leading cause of cancer death in western societies. In Finland, the incidence of CRC is 25/100.000, and 20/100.000 among males and females, respectively. Annually, 1.150 new cases are detected among males and 1.200 among women, representing 9.2% and 10% of all cancer cases, respectively (Finnish Cancer Registry, 2005. On the other hand, according to Benghazi Cancer Registry, 2003 [5] the colorectal cancer in eastern part of Libya is the most second frequent cancer after lung cancer in males and breast cancer in females. The average crude incidence rate is 6.4 (male and 5.2 (female cases per 100,000 inhabitants, representing 10.1% of male patients and 9.3% of female patients of all cancer cases.

  7. Prognostic value and importance of surgery combined with postoperative radiotherapy for oral and oropharyngeal cancer

    International Nuclear Information System (INIS)

    The aim of this paper is to evaluate the efficacy of surgery for patients with oral cavity or oropharyngeal cancer, and is impact on the final results of treatment combined with postoperative radiotherapy. Furthermore, predictive and prognostic value of clinical and histopatological postoperative factors were analysed, and estimation of clinical applicability of modified scale for risk of postoperative local and/or nodal recurrence according to Peters was checked. Material includes 218 cases of the advanced oral cavity or oropharyngeal cancer. All data were subdivided into 4 groups depending on treatment strategy. For the analysis of the treatment efficacy (overall and disease-free survival) many predictive and prognostic factors have been considered. Despite of multivariate logistic regression analysis of these factors, the risk of local recurrence was related to the results of combined treatment based on the modified numerical risk scale adapted from Peters. The risk value is the sum of scores given to individual prognostic factors. Time interval between surgery and radiotherapy (TI) and overall treatment time (TTT) have been accounted for the analysis. Generally; optimal results were noted in the group B, where surgery has been combined with postoperative radiotherapy. In case of surgery combined with preoperative radiotherapy (group E) 5-year DFS was 30%, and in the case when radiotherapy was delayed and applied when recurrence after primary surgery has occurred, the 5-year DFS was not higher than 20%. Macro- and microscopic surgical radicalism has been found one of the most important and significant prognostic factors. For positive margins (m+) 5-year DFS significantly decreases to about 20%. Surgical macro- and microradicalism has an important impact (p = 0.013) on the incidence of distant metastases. The scoring system for the recurrence was based on Peters scale. The sum of the risk scores (TRRI+n) for individual prognostic factors allow to allocate

  8. Molecular profiling of multiple human cancers defines an inflammatory cancer-associated molecular pattern and uncovers KPNA2 as a uniform poor prognostic cancer marker.

    Directory of Open Access Journals (Sweden)

    Saleh M Rachidi

    Full Text Available BACKGROUND: Immune evasion is one of the recognized hallmarks of cancer. Inflammatory responses to cancer can also contribute directly to oncogenesis. Since the immune system is hardwired to protect the host, there is a possibility that cancers, regardless of their histological origins, endow themselves with a common and shared inflammatory cancer-associated molecular pattern (iCAMP to promote oncoinflammation. However, the definition of iCAMP has not been conceptually and experimentally investigated. METHODS AND FINDINGS: Genome-wide cDNA expression data was analyzed for 221 normal and 324 cancer specimens from 7 cancer types: breast, prostate, lung, colon, gastric, oral and pancreatic. A total of 96 inflammatory genes with consistent dysregulation were identified, including 44 up-regulated and 52 down-regulated genes. Protein expression was confirmed by immunohistochemistry for some of these genes. The iCAMP contains proteins whose roles in cancer have been implicated and others which are yet to be appreciated. The clinical significance of many iCAMP genes was confirmed in multiple independent cohorts of colon and ovarian cancer patients. In both cases, better prognosis correlated strongly with high CXCL13 and low level of GREM1, LOX, TNFAIP6, CD36, and EDNRA. An "Inflammatory Gene Integrated Score" was further developed from the combination of 18 iCAMP genes in ovarian cancer, which predicted overall survival. Noticeably, as a selective nuclear import protein whose immuno-regulatory function just begins to emerge, karyopherin alpha 2 (KPNA2 is uniformly up-regulated across cancer types. For the first time, the cancer-specific up-regulation of KPNA2 and its clinical significance were verified by tissue microarray analysis in colon and head-neck cancers. CONCLUSION: This work defines an inflammatory signature shared by seven epithelial cancer types and KPNA2 as a consistently up-regulated protein in cancer. Identification of iCAMP may not only

  9. Ovarian Cancer Stem Cell Markers: Prognostic and Therapeutic Implications

    OpenAIRE

    Burgos-Ojeda, Daniela; Rueda, Bo R.; Buckanovich, Ronald J.

    2012-01-01

    Cancer stem cells are rare chemotherapy resistant cells within a tumor which can serve to populate the bulk of a tumor with more differentiated daughter cells and potentially contribute to recurrent disease. Ovarian cancer is a disease for which at the time of initial treatment we can obtain complete clinical remission in the majority of patients. Unfortunately, most will relapse and succumb to their disease. This clinical course is in line with the cancer stem cell model. In the past five ye...

  10. Discovery and validation of prognostic markers in gastric cancer by genome-wide expression profiling

    Directory of Open Access Journals (Sweden)

    Yue-Zheng Zhang, Lian-Hai Zhang, Yang Gao, Chao-Hua Li, Shu-Qin Jia, Ni Liu, Feng Cheng, De-Yun Niu, William CS Cho, Jia-Fu Ji, Chang-Qing Zeng

    2011-04-01

    Full Text Available AIM: To develop a prognostic gene set that can predict patient overall survival status based on the whole genome expression analysis.METHODS: Using Illumina HumanWG-6 BeadChip followed by semi-supervised analysis, we analyzed the expression of 47 296 transcripts in two batches of gastric cancer patients who underwent surgical resection. Thirty-nine samples in the first batch were used as the training set to discover candidate markers correlated to overall survival, and thirty-three samples in the second batch were used for validation.RESULTS: A panel of ten genes were identified as prognostic marker in the first batch samples and classified patients into a low- and a high-risk group with significantly different survival times (P = 0.000047. This prognostic marker was then verified in an independent validation sample batch (P = 0.0009. By comparing with the traditional Tumor-node-metastasis (TNM staging system, this ten-gene prognostic marker showed consistent prognosis results. It was the only independent prognostic value by multivariate Cox regression analysis (P = 0.007. Interestingly, six of these ten genes are ribosomal proteins, suggesting a possible association between the deregulation of ribosome related gene expression and the poor prognosis.CONCLUSION: A ten-gene marker correlated with overall prognosis, including 6 ribosomal proteins, was identified and verified, which may complement the predictive value of TNM staging system.

  11. The role of squamous cell carcinoma antigen as a prognostic and predictive factor in carcinoma of uterine cervix

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Bae Kwon; Choi, Doo Ho; Huh, Seung Jae; Park, Won; Bae, Duk Soo; Kim, Byoung Gie [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2011-09-15

    Although the role of squamous cell carcinoma antigen (SCC-Ag) as a predictive and prognostic factor for uterine cervical cancer has been identified ed in previous studies, 1) the effective patient group of screening for recurrence with SCC-Ag, 2) the relationship between SCC-Ag and recurrence site, and 3) the relationship between the change of SCC-Ag and treatment outcome or recurrence have not been described. The study included 506 patients with histologically proven uterine cervical cancer between January 1994 and December 2010. We determining the serum SCC-Ag level before treatment and after treatment, and conducted a retrospective review of the patients' records. We evaluated the sensitivity and specificity of SCC-Ag for the detection of tumor recurrence by comparing biochemical recurrence with clinical recurrence. The pretreatment SCC-Ag level and the proportion of patients over 1.5 ng/mL were higher in poor prognostic patient group. In the univariate and multivariate analysis, pretreatment SCC-Ag showed a statistically significant correlation with tumor size, International Federation of Gynecology and Obstetrics (FIGO) stage, pathology. In patients with biochemical recurrence vs. those without, 5-year DFS and OS were 27.6 vs. 92.7% (p{<=}0.001) and 53.7 vs. 92.5% (p{<=}0.001), respectively. Our study reconfirmed the known function of pretreatment SCC-Ag, but could not confirm the function of biochemical response as a predictive factor for treatment and as a prognostic factor. There was no statistically significant relationship between SCC-Ag level and recurrence site. We confirmed the role of SCC-Ag as a follow-up tool for recurrence of disease and which patient groups SCC-Ag was more useful for.

  12. Diagnostic and prognostic signatures from the small non-coding RNA transcriptome in prostate cancer

    DEFF Research Database (Denmark)

    Martens-Uzunova, E S; Jalava, S E; Dits, N F;

    2011-01-01

    Prostate cancer (PCa) is the most frequent male malignancy and the second most common cause of cancer-related death in Western countries. Current clinical and pathological methods are limited in the prediction of postoperative outcome. It is becoming increasingly evident that small non-coding RNA...... RNAs (snoRNAs) and transfer RNAs (tRNAs). From microarray analysis, we derived a miRNA diagnostic classifier that accurately distinguishes normal from cancer samples. Furthermore, we were able to construct a PCa prognostic predictor that independently forecasts postoperative outcome. Importantly, the...

  13. Prognostic protein markers for triple negative breast cancer

    NARCIS (Netherlands)

    A. Umar (Arzu); N.Q. Liu (Ning Qing); R.B.H. Braakman (René)

    2010-01-01

    textabstractBreast cancer is the most commonly diagnosed malignancy in women in the Western world, with 13,000 new patients each year in the Netherlands alone. Extensive research on gene expression profiling has shown that breast cancer is a mixture of biologically different disease entities, referr

  14. Prognostic implication of apoptosis and angiogenesis in cervical uteri cancer

    International Nuclear Information System (INIS)

    Purpose: A retrospective study was performed to investigate the relationship between spontaneous apoptosis and angiogenesis uterine cervix squamous cell carcinoma patients. The prognostic value of each (and both) of these biologic parameters was also tested. Methods and Materials: The pathologic materials of 40 cervical uteri squamous cell carcinoma patients were examined and immunohistochemically stained to determine the tumor angiogenesis (tumor microvascular score), using factor VIII-related antigen, and their tumor apoptotic index (AI), using the TdT-mediated dUTP nick end-labeling (TUNEL) method. Three patients were Stage I, 18 were Stage II, 15 were Stage III, and 4 were Stage IV (FIGO classification). All patients were treated with radical radiotherapy and all had follow-up for more than 2 years. Results: The mean AI was 15.1 ± 12.8, with a median of 8.3. The mean tumor microvascular score was 3 9.7 ± 14.4, with a median of 3 8. The patients' age and tumor grade did not seem to significantly affect the prognosis. On the other hand, AI and angiogenesis (tumor microvascular score) were of high prognostic significance. The 3-year disease-free survival (DFS) rate for the patients having AI above the median was 78% (confidence interval [CI] 69-87%), compared to 32% (CI 22-42%) for those having AI below the median. The DFS was 18% (CI 9-27%) for patients having an angiogenesis score above the median, while it was 86% (CI 78-94%) for those patients having a score below the median. Conclusion: Determination of both tumor microvascular score and AI can identify patients with the best prognosis of 100% DFS (with low angiogenesis score and high AI). Women with a high score and low AI had the worst prognosis (DFS = 3%, CI 1-5%). Moreover, high AI can compensate partially for the aggressive behavior of tumors showing a high rate of angiogenesis.

  15. Prognostic factors for survivals from first relapse in breast cancer patients: analysis of deceased patients

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hae Young [Dept.of Radiation Oncology, Hallym University Dongtan Sacred Heart Hospital, Hwaseong (Korea, Republic of); Choi, Doo Ho; Park, Won; Huh, Seung Jae; Nam, Seok Jin; Lee, Jeong Eon; Ahn, Jin Seok; Im, Young Hyuck [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2013-12-15

    This study was performed to evaluate prognostic factors for survival from first relapse (SFFR) in stage I-III breast cancer patients. From June 1994 to June 2008, 3,835 patients were treated with surgery plus postoperative radiotherapy and adjuvant chemotherapy for stage I-III breast cancer at Samsung Medical Center. Among them, a total of 224 patients died by June 2009, and 175 deaths were of breast cancer. Retrospective review was performed on medical records of 165 patients who met the inclusion criteria of this study. Univariate and multivariate analysis were done on survivals according to variables, such as age, stage, hormone status of tumor, disease-free interval (DFI), sites of first failure, number of organs involved by recurrent disease (NOR), application of salvage treatments, and existence of brain or liver metastasis (visceral metastasis). Patients' median overall survival time was 38 months (range, 8 to 123 months). Median SFFR was 17 months (range, 5 to 87 months). Ninety percent of deaths occurred within 40 months after first recurrence. The patients with SFFR 1 year had tendency of triple-negativity, shorter DFI 2 years), larger NOR (>3), visceral metastasis for first relapse than the patients with SFFR >1 year. In multivariate analysis, longer DFI (>2 vs. 2 years), absence of visceral metastasis, and application of salvage treatments were statistically significant prognosticators for longer SFFR. The DFI, application of salvage treatments, and visceral metastasis were significant prognostic factors for SFFR in breast cancer patients.

  16. Prognostic factors of T4 gastric cancer patients undergoing potentially curative resection

    Institute of Scientific and Technical Information of China (English)

    Naoto Fukuda; Yasuyuki Sugiyama; Joji Wada

    2011-01-01

    AIM: To investigate the prognostic factors of T4 gas-tric cancer patients without distant metastasis who could undergo potentially curative resection. METHODS: We retrospectively analyzed the clinical data of 71 consecutive patients diagnosed with T4 gas-tric cancer and who underwent curative gastrectomy at our institutions. The clinicopathological factors that could be associated with overall survival were evalu-ated. The cumulative survival was determined by the Kaplan-Meier method, and univariate comparisons be-tween the groups were performed using the log-rank test. Multivariate analysis was performed using the Cox proportional hazard model and a step-wise procedure.RESULTS: The study patients comprised 53 men (74.6%) and 18 women (25.4%) aged 39-89 years (mean, 68.9 years). Nineteen patients (26.8%) had postoperative morbidity: pancreatic fistula developed in 6 patients (8.5%) and was the most frequent compli-cation, followed by anastomosis stricture in 5 patients (7.0%). During the follow-up period, 28 patients (39.4%) died because of gastric cancer recurrence, and 3 (4.2%) died because of another disease or accident. For all patients, the estimated overall survival was 34.1% at 5 years. Univariate analyses identified the following statis-tically significant prognostic factors in T4 gastric cancer patients who underwent potentially curative resection: peritoneal washing cytology (P < 0.01), number of met-astatic lymph nodes (P < 0.05), and venous invasion (P < 0.05). In multivariate analyses, only peritoneal wash-ing cytology was identified as an independent prognos-tic factor (HR = 3.62, 95% CI = 1.37-9.57) for long-term survival. CONCLUSION: Positive peritoneal washing cytology was the only independent poor prognostic factor for T4 gastric cancer patients who could be treated with potentially curative resection.

  17. Survival probability and prognostic factors for breast cancer patients in Vietnam

    Directory of Open Access Journals (Sweden)

    Nguyen H. Lan

    2013-01-01

    Full Text Available Background: Breast cancer is becoming a public health problem in Vietnam. The mortality to incidence ratio of the disease was ranked second among the most common cancers in women. This study estimates the survival probability at 1, 3, and 5 years following diagnosis and determines prognostic factors for breast cancer mortality in Vietnam. Methods: A survival analysis was conducted based on retrospective data from Hue Central Hospital and the Cancer Registry in Ho Chi Minh City. Using the Kaplan-Meier method, the survival probability of patients with breast cancer was estimated at 1, 3, and 5 years following diagnosis. The covariates among prognostic factors for survival time were studied using an extended Cox proportion hazards model, including time-dependent predictors. Results: Overall survival rates at 1, 3, and 5 years following diagnosis were 0.94, 0.83 and 0.74 respectively. Marital status, education level, stage at diagnosis, and hormone therapy were prognostic factors for mortality. For the stage at diagnosis, the relation to the risk of death for breast cancer was 1.32 (95% CI, 1.22–1.41. Married women faced a risk of death nearly 1.59 times higher than unmarried women (95% CI, 1.09–2.33. Women with higher levels of education and who received hormone therapy had approximately 10% (hazard ratio [HR]: 0.92; 95% CI, 0.89–0.96 and 80% (HR: 0.22; 95% CI, 0.12–0.41 risk reduction of death respectively, compared with those classified as illiterate and those without hormone therapy. Conclusions: The 5-year survival probability of breast cancer was lower in Vietnam than in countries with similar distributions of the stage at diagnosis. Screening programs and related support policies should be developed to increase the life expectancy of women with breast cancer in Vietnam.

  18. Clinicodemographic aspect of resectable pancreatic cancer and prognostic factors for resectable cancer

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    Chiang Kun-Chun

    2012-05-01

    Full Text Available Abstract Background Pancreatic adenocarcinoma (PCA is one of the most lethal human malignancies, and radical surgery remains the cornerstone of treatment. After resection, the overall 5-year survival rate is only 10% to 29%. At the time of presentation, however, about 40% of patients generally have distant metastases and another 40% are usually diagnosed with locally advanced cancers. The remaining 20% of patients are indicated for surgery on the basis of the results of preoperative imaging studies; however, about half of these patients are found to be unsuitable for resection during surgical exploration. In the current study, we aimed to determine the clinicopathological characteristics that predict the resectability of PCA and to conduct a prognostic analysis of PCA after resection to identify favorable survival factors. Methods We retrospectively reviewed the medical files of 688 patients (422 men and 266 women who had undergone surgery for histopathologically proven PCA in the Department of Surgery at Chang Gung Memorial Hospital in Taiwan from 1981 to 2006. We compared the clinical characteristics of patients who underwent resection and patients who did not undergo resection in order to identify the predictive factors for successful resectability of PCA, and we conducted prognostic analysis for PCA after resection. Results A carbohydrate antigen 19–9 (CA 19–9 level of 37 U/ml or greater and a tumor size of 3 cm or more independently predicted resectability of PCA. In terms of survival after resection, PCA patients with better nutritional status (measured as having an albumin level greater than 3.5 g/dl, radical resection, early tumor stage and better-differentiated tumors were associated with favorable survival. Conclusions Besides traditional imaging studies, preoperative CA 19–9 levels and tumor size can also be used to determine the resectability of PCA. Better nutritional status, curative resection, early tumor stage and well

  19. Prognostic value of scores based on malnutrition or systemic inflammatory response in patients with metastatic or recurrent gastric cancer.

    Science.gov (United States)

    Sachlova, Milana; Majek, Ondrej; Tucek, Stepan

    2014-01-01

    Cancer patients are frequently affected by malnutrition and weight loss, which affects their prognosis, length of hospital stay, health care costs, quality of life and survival. Our aim was to assess the prognostic value of different scores based on malnutrition or systemic inflammatory response in 91 metastatic or recurrent gastric cancer patients considered for palliative chemotherapy at the Masaryk Memorial Cancer Institute. We investigated their overall survival according to the following measures: Onodera's Prognostic Nutritional Index (OPNI), Glasgow Prognostic Score (GPS), nutritional risk indicator (NRI), Cancer Cachexia Study Group (CCSG), as previously defined, and a simple preadmission weight loss. The OPNI, GPS, and CCSG provided very significant prognostic values for survival (log-rank test P value evaluation of patients' prognosis and should be part of a routine evaluation of patients to provide a timely nutrition support. PMID:25356861

  20. Current Challenges in Development of Differentially Expressed and Prognostic Prostate Cancer Biomarkers

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    Steven M. Lucas

    2012-01-01

    Full Text Available Introduction. Predicting the aggressiveness of prostate cancer at biopsy is invaluable in making treatment decisions. In this paper we review the differential expression of genes and microRNAs identified through microarray analysis as potentially useful markers for prostate cancer prognosis and discuss some of the challenges associated with their development. Methods. A review of the literature was conducted through Medline. Articles were identified through searches of the following terms: “prostate cancer AND differential expression”, “prostate cancer prognosis”, and “prostate cancer AND microRNAs”. Results. Though numerous differentially expressed genes and microRNAs were identified as possible prognostic markers, the significance of several of these genes is either debated due to conflicting results or is not validated in other study populations. A few of the articles constructed predictive nomograms using a panel of biomarkers which require further validation. Challenges to the development of useful markers include different methodology, cancer heterogeneity, and sampling error. These can be overcome by categorizing prognostic factors into particular gene pathways or by supplementing biopsy information with blood or urine-based biomarkers. Conclusion. Though biomarkers based on differential expression offer the potential to improve decision making concerning prostate cancer, further validation of their utility and accuracy at the biopsy level is needed.

  1. Tissue Biomarkers in Prognostication of Serous Ovarian Cancer following Neoadjuvant Chemotherapy

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    Binny Khandakar

    2014-01-01

    Full Text Available Serous ovarian cancer (SOC is a significant cause of morbidity and mortality in females with poor prognosis because of advanced stage at presentation. Recently, neoadjuvant chemotherapy (NACT is being used for management of advanced SOC, but role of tissue biomarkers in prognostication following NACT is not well established. The study was conducted on advanced stage SOC patients (n=100 that were treated either conventionally (n=50 or with NACT (n=50, followed by surgery. In order to evaluate the expression of tissue biomarkers (p53, MIB1, estrogen and progesterone receptors, Her-2/neu, E-cadherin, and Bcl2, immunohistochemistry and semiquantitative scoring were done following morphological examination. Following NACT, significant differences in tumor histomorphology were observed as compared to the native neoplasms. MIB 1 was significantly lower in cases treated with NACT and survival outcome was significantly better in cases with low MIB 1. ER expression was associated with poor overall survival. No other marker displayed any significant difference in expression or correlation with survival between the two groups. Immunophenotype of SOC does not differ significantly in samples from cases treated with NACT, compared to upfront surgically treated cases. The proliferating capacity of the residual tumor cells is less, depicted by low mean MIB1 LI. MIB 1 and ER inversely correlate with survival.

  2. Candidate prognostic markers in breast cancer: focus on extracellular proteases and their inhibitors

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    Roy DM

    2014-07-01

    Full Text Available David M Roy,1 Logan A Walsh21Weill Cornell/Rockefeller/Sloan-Kettering Tri-Institutional MD-PhD Program, New York, NY, USA; 2Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY, USAAbstract: The extracellular matrix (ECM is the complex network of proteins that surrounds cells in multicellular organisms. Due to its diverse nature and composition, the ECM has a multifaceted role in both normal tissue homeostasis and pathophysiology. It provides structural support, segregates tissues from one another, and regulates intercellular communication. Furthermore, the ECM sequesters a wide range of growth factors and cytokines that may be released upon specific and well-coordinated cues. Regulation of the ECM is performed by the extracellular proteases, which are tasked with cleaving and remodeling this intricate and diverse protein matrix. Accordingly, extracellular proteases are differentially expressed in various tissue types and in many diseases such as cancer. In fact, metastatic dissemination of tumor cells requires degradation of extracellular matrices by several families of proteases, including metalloproteinases and serine proteases, among others. Extracellular proteases are emerging as strong candidate cancer biomarkers for aiding and predicting patient outcome. Not surprisingly, inhibition of these protumorigenic enzymes in animal models of metastasis has shown impressive therapeutic effects. As such, many of these proteolytic inhibitors are currently in various phases of clinical investigation. In addition to direct approaches, aberrant expression of extracellular proteases in disease states may also facilitate the selective delivery of other therapeutic or imaging agents. Herein, we outline extracellular proteases that are either bona fide or probable prognostic markers in breast cancer. Furthermore, using existing patient data and multiple robust statistical analyses, we highlight several

  3. Urachal cancer: contemporary review of the pathological, surgical, and prognostic aspects of this rare disease.

    Science.gov (United States)

    Behrendt, Mark A; DE Jong, Jeroen; VAN Rhijn, Bas W

    2016-04-01

    Surgery is the mainstay of treatment for patients with urachal cancer (UraC). Still, one third of patients are un-resectable at presentation. Histology shows adenocarcinomas in the majority of cases with resemblance to enteric tumors. Standard chemotherapeutic regimens for bladder cancer have failed these patients. The role and efficacy of radiotherapy remains unclear due to its use in combination with chemotherapy or in a palliative setting. A lack of background knowledge about this disease leaves practitioners with unanswered questions when recommending (neo)adjuvant or palliative treatment options. Despite the lack of large multicenter series or randomized studies, independent case series have found commonalities with gastric, colorectal or ovarian cancers. Better clinical staging, advanced surgical techniques and a variety of (neo)adjuvant therapy combinations spawn hope for improved survival for these patients. Genetic and immunohistochemical studies are debating a common origin of this disease. Meta-analyses of clinical data are showing prognosticators and risk factors. UraC is a rare disease characterized by malignant degeneration of the urachal remnant with the highest incidence in fifty to sixty year old individuals. Unlike bladder cancer, the majority of UraC cases are adenocarcinomas. Its classical location at the bladder dome, advanced stage at presentation and symptoms like hematuria and mucinuria, should make the clinician suspicious. It is important to look for metastases or mucous cysts during clinical staging to determine the possibility of a curative approach. Up to date, surgery including on-bloc resection of the urachal ligament, the bladder dome and the umbilicus is the only proven cure. R0 resection is crucial for recurrence free survival. Adjuvant or palliative therapy can prolong survival in un-resectable or recurrent disease. While curative patients have a survival well above 50% over five years, palliative patients average only two years

  4. Prognostic protein markers for triple negative breast cancer

    OpenAIRE

    Umar, Arzu; Liu, Ning Qing; Braakman, René

    2010-01-01

    textabstractBreast cancer is the most commonly diagnosed malignancy in women in the Western world, with 13,000 new patients each year in the Netherlands alone. Extensive research on gene expression profiling has shown that breast cancer is a mixture of biologically different disease entities, referred to as molecular subtypes. Of all molecular subtypes, particularly the triple negative phenotype associates with poor prognosis and poor patient survival. Intriguingly, only a small subgroup of t...

  5. Hereditary Colorectal Cancer: Registration, Screening and Prognostic Biomarker Analysis

    OpenAIRE

    Barrow, Paul

    2015-01-01

    Aims: The purpose of the research was to investigate the benefits of a hereditary colorectal cancer registry in the management of patients and families with Lynch syndrome. In study one, a systematic review was performed to quantify the impact of registration and screening on colorectal cancer (CRC) incidence and mortality, with comparison between familial adenomatous polyposis (FAP) and Lynch syndrome (LS). In study two, a regional Lynch syndrome registry was utilised to evaluate the uptake ...

  6. 14-3-3σ is an independent prognostic biomarker for gastric cancer and is associated with apoptosis and proliferation in gastric cancer.

    Science.gov (United States)

    Li, Yi-Liang; Liu, Lihua; Xiao, Yang; Zeng, Tao; Zeng, Chao

    2015-01-01

    14-3-3 proteins participate in various cellular processes, including apoptosis, proliferation and malignant transformation. 14-3-3σ, a member of the 14-3-3 protein family, is important in several types of cancer; however, little is known about the clinical significance and biological roles of 14-3-3σ in gastric cancer. The present study analyzed the expression pattern of 14-3-3σ in gastric cancer and investigated its correlation with the prognosis of gastric cancer patients. Furthermore, the association of 14-3-3σ with Ki-67, Bcl-2 and Bax was evaluated. 14-3-3σ was expressed at higher level in gastric cancer tissue compared with healthy gastric tissue, and 14-3-3σ expression was significantly correlated with tumor size and tumor node metastasis stage (Pknowledge, the present study data are the first to suggest that 14-3-3σ expression has been significantly associated with poor prognosis in gastric cancer. Additionally, 14-3-3σ overexpression was positively correlated with Ki-67 and Bcl-2 expression levels. Thus, 14-3-3σ is a potential prognostic marker for gastric cancer patients, and may be involved in regulating the apoptosis and proliferation of gastric cancer cells. PMID:25435977

  7. Clinicopathologic characteristics and prognostic factors of 63 gastric cancer patients with metachronous ovarian metastasis

    International Nuclear Information System (INIS)

    This study aims to explore the clinicopathologic characteristics and prognostic factors of gastric cancer patients with metachronous ovarian metastasis. Clinicopathologic data were collected from 63 post-operative gastric cancer patients with metachronous ovarian metastasis. The patients were admitted to the Cancer Institute and Hospital, Chinese Academy of Medical Science and Peking Union Medical College between January 1999 and December 2011. A log-rank test was conducted for survival analysis. Possible prognostic factors that affect survival were examined by univariate analysis. A Cox regression model was used for multivariate analysis. The incidence of ovarian metastasis was 3.4% with a mean age of 45 years. Up to 65.1% of the patients were pre-menopausal. The mean interval between ovarian metastasis and primary cancer was 16 months. Lowly differentiated carcinoma ranked first in the primary gastric cancers. The majority of lesions occurred in the serous membrane (87.3%). The metastatic sites included N2-3 lymph nodes (68.3%), bilateral ovaries (85.7%), and peritoneal membrane (73%). Total resection of metastatic sites was performed (31.7%). The overall median survival was 13.6 months, whereas the overall 1-, 2-, and 3-year survival rates were 52.5%, 22.0%, and 9.8%, respectively. The 5-year survival rate was zero. Univariate analysis showed that the patient prognosis was correlated with metastatic peritoneal seeding, vascular tumor embolus, range of lesion excision, and mode of comprehensive treatment with adjuvant chemotherapy (P<0.05). Multivariate analysis indicated that metastatic peritoneal seeding was an independent prognostic factor for gastric cancer patients with ovarian metastasis (P<0.01). Effective control of peritoneal seeding—induced metastasis is important for improving the prognosis of gastric cancer patients with ovarian metastasis

  8. Treatment for liver metastases from breast cancer: Results and prognostic factors

    Institute of Scientific and Technical Information of China (English)

    Xiao-Ping Li; Zhi-Qiang Meng; Wei-Jian Guo; Jie Li

    2005-01-01

    AIM: Liver metastases from breast cancer (BCLM) are associated with poor prognosis. Cytotoxic chemotherapy can result in regression of tumor lesions and a decrease in symptoms. Available data, in the literature, also suggest a subgroup of patients rraay berefit from surgery, but few talked about transcatheter arterial chemoembolization (TACE).We report the results of TACE and systemic chemotherapy for patients with liver metastases from breast cancer and evaluate the prognostic factors. METHODS: Forty-eight patients with liver metastases, from proved breast primary cancer were treated with TACEor systemic chemotherapy between January 1995 and December 2000. Treatment results were assessed according to WHO criteria, along with analysis of prognostic factors for survival using Cox regression model.RESULTS: The median follow-up was 28 mo (1-72 mo). Response rates were calculated for the TACE group and chemotherapy group, being 35.7% and 7.1%,respectively. The difference was significant. The one-, two- and three-year Survival rates for the TACE group were 63.04%, 30.35%, and 13.01%, and those for the systemic chemotherapy group were 33.88%, 11.29%, and 0%. According to univariate analysis, variables significantly associated with survival were the lymph node status of the primary cancer, the clinical stage of liver metastases, the Child-Pugh grade, loss of weight. Other factors such as age, the intervals between the primary to the metastases, the maximal diameter of the liver metastases, the number of liver metastases, extrahepatic metastasis showed no prognostic significances. These factors mentioned above such as the lymph node status of the primary cancer, the clinical stage of liver metastases, the Child-Pugh grade, loss of weight were also independent factors in multivariate analysis.CONCLUSION: TACE treatment of liver metastases from breast cancer may prolong survival in certain patients. This approach offers new promise for the curative treatment of the patients

  9. Role of lymphangiogenesis in lung cancer.

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    Renata Jankowska

    2010-02-01

    Full Text Available Lung cancer represents one of the most frequent causes of death due to neoplastic disease in Poland and around the world. The high mortality which accompany neoplastic diseases used to be ascribed mainly to dissemination of cancerous cells. Studies on animal models suggest that tumour lymphangiogenesis represents the principal factor in the process of metastases formation. Lymphangiogenesis involves a process of formation of new lymphatic vessels from already existing lymphatic capillaries. Lymphangiogenesis is stimulated by vascular endothelial growth factors (VEGF and other, recently reported factors, such as, e.g., cyclooxygenase 2, fibroblast growth factor 2, angiopoetin-1 and the insulin-resembling growth factor. In lymphangiogenesis a key role is played by neutropilin 2 or podoplanin and this promoted development of studies on lymphangiogenesis. Activation of VEGF-C/VEGF-D/VEGFR-3 axis increases motility and invasiveness of neoplastic cells, promotes development of metastases in several types of tumours such as, e.g., lung cancer, mammary carcinoma, cancers of the neck, prostate and large intestine. In recent years lymphangiogenesis provided topic of many studies. A positive correlation was detected between expressions of VEGF-C/D and VEGFR-3 in non-small cell lung cancer. In patients with lung cancer with high expression of VEGF-C a markedly abbreviated survival was noted. Positive correlation was detected between expression of VEGF-C and VEGF-D on one hand and expression of LYVE-1 on the other in sentinel lymph nodes with metastases of neoplastic cells in patients with non-small cell lung cancer. Also, high density of lymphatic vessels and high density of intraneoplastic microvessels proved to be independent poor prognostic indices in patients with non-small cell lung cancer. Extensive hope is linked to studies on inhibitors of lymphangiogenesis, which may improve results of treatment also in tumour patients.

  10. A Laboratory Prognostic Index Model for Patients with Advanced Non-Small Cell Lung Cancer

    OpenAIRE

    Arife Ulas; Fatma Paksoy Turkoz; Kamile Silay; Saadet Tokluoglu; Nilufer Avci; Berna Oksuzoglu; Necati Alkis

    2014-01-01

    Purpose We aimed to establish a laboratory prognostic index (LPI) in advanced non-small cell lung cancer (NSCLC) patients based on hematologic and biochemical parameters and to analyze the predictive value of LPI on NSCLC survival. Patients and Methods The study retrospectively reviewed 462 patients with advanced NSCLC diagnosed between 2000 and 2010 in a single institution. We developed an LPI that included serum levels of white blood cells (WBC), lactate dehydrogenase (LDH), albumin, calciu...

  11. Novel serum protein biomarker panel revealed by mass spectrometry and its prognostic value in breast cancer

    OpenAIRE

    Chung, Liping; Moore, Katrina; Phillips, Leo; Boyle, Frances M.; Marsh, Deborah J.; Baxter, Robert C.

    2014-01-01

    Introduction Serum profiling using proteomic techniques has great potential to detect biomarkers that might improve diagnosis and predict outcome for breast cancer patients (BC). This study used surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry (MS) to identify differentially expressed proteins in sera from BC and healthy volunteers (HV), with the goal of developing a new prognostic biomarker panel. Methods Training set serum samples from 99 BC and 51 H...

  12. Osteopontin is a prognostic biomarker in non-small cell lung cancer

    OpenAIRE

    Rud, Ane Kristine Kongsgaard; Pedersen, Kjetil Boye; Øijordsbakken, Miriam; Lund-Iversen, Marius; Halvorsen, Ann Rita; Solberg, Steinar; Berge, Gisle; Helland, Åslaug; Brustugun, Odd Terje; Mælandsmo, Gunhild

    2013-01-01

    Background: In a previously published report we characterized the expression of the metastasis-associated proteins S100A4, osteopontin (OPN) and ephrin-A1 in a prospectively collected panel of non-small cell lung cancer (NSCLC) tumors. The aim of the present follow-up study was to investigate the prognostic impact of these potential biomarkers in the same patient cohort. In addition, circulating serum levels of OPN were measured and single nucleotide polymorphisms (SNP) in the −44...

  13. Radiomic Machine Learning Classifiers for Prognostic Biomarkers of Head & Neck Cancer

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    Chintan eParmar

    2015-12-01

    Full Text Available Introduction: Radiomics extracts and mines large number of medical imaging features in a non-invasive and cost-effective way. The underlying assumption of radiomics is that these imaging features quantify phenotypic characteristics of entire tumor. In order to enhance applicability of radiomics in clinical oncology, highly accurate and reliable machine learning approaches are required. In this radiomic study, thirteen feature selection methods and eleven machine learning classification methods were evaluated in terms of their performance and stability for predicting overall survival in head and neck cancer patients. Methods: Two independent head and neck cancer cohorts were investigated. Training cohort HN1 consisted 101 HNSCC patients. Cohort HN2 (n=95 was used for validation. A total of 440 radiomic features were extracted from the segmented tumor regions in CT images. Feature selection and classification methods were compared using an unbiased evaluation framework. Results: We observed that the three feature selection methods MRMR (AUC = 0.69, Stability = 0.66, MIFS (AUC = 0.66, Stability = 0.69, and CIFE (AUC = 0.68, Stability = 0.7 had high prognostic performance and stability. The three classifiers BY (AUC = 0.67, RSD = 11.28, RF (AUC = 0.61, RSD = 7.36, and NN (AUC = 0.62, RSD = 10.52 also showed high prognostic performance and stability. Analysis investigating performance variability indicated that the choice of classification method is the major factor driving the performance variation (29.02% of total variance. Conclusions: Our study identified prognostic and reliable machine learning methods for the prediction of overall survival of head and neck cancer patients. Identification of optimal machine-learning methods for radiomics based prognostic analyses could broaden the scope of radiomics in precision oncology and cancer care.

  14. Circulating cell-free DNA and its integrity as a prognostic marker for breast cancer

    OpenAIRE

    Iqbal, Sobuhi; Vishnubhatla, Sreenivas; Raina, Vinod; Sharma, Surabhi; Gogia, Ajay; Suryanarayana S.V. Deo; Mathur, Sandeep; Shukla, Nutan Kumar

    2015-01-01

    The aim of our study was to look for alternative predictive biomarkers for breast cancer management in limited resource setup. A comprehensive analysis of circulating cell-free DNA (CCFD) in serum at baseline was performed to assess its prognostic potential. Quantitative polymerase chain reaction (qPCR) of ALU sequences using ALU115 and ALU247 primers was carried out in patients (N: baseline 148, postoperative 47) and 51 healthy controls. Mean serum DNA integrity, levels of ALU 247 and levels...

  15. Clinicopathologic and prognostic significance of p21 (Cip1/Waf1) expression in bladder cancer

    OpenAIRE

    Tang, Kun; Wang, Chenghe; Chen, Zhong; Xu, Hua; Ye, Zhangqun

    2015-01-01

    Recent studies have shown that altered expression p21 is shown to associate with tumorigenesis and tumor progression. To investigate the clinicopathological significance and prognostic value of p21 in bladder cancer (BCa). A total of 48 patients with BCa were included in this study. The correlation between p21 expression and clinicopathologic features and survival was studied. Also, a meta-analysis was performed to investigate the relationship between the p21 and BCa survival. Low p21 express...

  16. Magnetic Resonance Imaging of Breast Cancer and Correlation with Prognostic Factors

    International Nuclear Information System (INIS)

    Background: Prognostic factors of breast cancer have been used for the prediction of clinical outcome or selection of patients for complementary treatment. Some of the imaging features of breast cancer, e.g. magnetic resonance imaging (MRI), are associated with these prognostic factors. Purpose: To evaluate the relationship between dynamic enhanced MR features and prognostic factors of clinical outcome of breast cancer. Material and Methods: A total of 136 patients with 151 breast cancers underwent 1.5T dynamic MR imaging with the use of a dynamic T1-weighted three-dimensional fast low-angle shot (FLASH) subtraction imaging technique. Morphological and kinetic analyses of MR features were evaluated using the American College of Radiology (ACR) Breast Imaging Reporting and Data System (BI-RADS) MRI lexicon. Pathological prognostic factors were correlated with MR imaging characteristics, including tumor size, histological grade, lymph node status, expression of estrogen receptor (ER), expression of progesterone receptor (PR), expression of c-erbB2, determination of Ki-67 index, and microvascular density (MVD), using univariate and multivariate statistical analyses. Results: Based on univariate and multivariate analyses, spiculated tumor margins correlated significantly with lower histological grade (I-II) and positive PR expression. Rim enhancement was significantly correlated with high histological grade, presence of axillary lymph node metastasis, large tumor size, increased Ki-67 index, and increased MVD. Early peak enhancement, as seen on the first scan after contrast medium injection, was correlated with negative ER expression. Conclusion: The presence of a lesion with a spiculated margin may predict a relatively good prognosis, and the presence of a lesion with rim enhancement may predict a relatively poor prognosis

  17. Prognostic significance of DNA repair proteins MLH1, MSH2 and MGMT expression in non-small-cell lung cancer and precursor lesions

    OpenAIRE

    Cooper, W. A.; Kohonen-Corish, M R J; Chan, C; Kwun, S Y; McCaughan, B; Kennedy, C; Sutherland, R.L.; Lee, C-S.

    2008-01-01

    Aims To investigate the role of DNA repair proteins and their prognostic significance in non-small-cell lung cancer (NSCLC). Methods and results A retrospective analysis of 108 cases of stage I–II NSCLC was undertaken. Immunohistochemical expression of DNA repair proteins MLH1, MSH2 and MGMT was assessed using tissue microarrays of paraffin-embedded samples of invasive carcinoma and precursor lesions. Results were analysed in relation to clinicopathological parameters and patient survival. Re...

  18. Distinct prognostic values of four-Notch-receptor mRNA expression in ovarian cancer.

    Science.gov (United States)

    Zhou, Xinling; Teng, Lingling; Wang, Min

    2016-05-01

    Notch signaling pathway includes ligands and Notch receptors, which are frequently deregulated in several human malignancies including ovarian cancer. Aberrant activation of Notch signaling has been linked to ovarian carcinogenesis and progression. In the current study, we used the "Kaplan-Meier plotter" (KM plotter) database, in which updated gene expression data and survival information from a total of 1306 ovarian cancer patients were used to access the prognostic value of four Notch receptors in ovarian cancer patients. Hazard ratio (HR), 95 % confidence intervals, and log-rank P were calculated. Notch1 messenger RNA (mRNA) high expression was not found to be correlated to overall survival (OS) for all ovarian cancer, as well as in serous and endometrioid cancer patients followed for 20 years. However, Notch1 mRNA high expression is significantly associated with worsen OS in TP53 wild-type ovarian cancer patients, while it is significantly associated with better OS in TP53 mutation-type ovarian cancer patients. Notch2 mRNA high expression was found to be significantly correlated to worsen OS for all ovarian cancer patients, as well as in grade II ovarian cancer patients. Notch3 mRNA high expression was found to be significantly correlated to better OS for all ovarian cancer patients, but not in serous cancer patients and endometrioid cancer patients. Notch4 mRNA high expression was not found to be significantly correlated to OS for all ovarian cancer patients, serous cancer patients, and endometrioid cancer patients. These results indicate that there are distinct prognostic values of four Notch receptors in ovarian cancer. This information will be useful for better understanding of the heterogeneity and complexity in the molecular biology of ovarian cancer and for developing tools to more accurately predict their prognosis. Based on our results, Notch1 could be a potential drug target of TP53 wild-type ovarian cancer and Notch2 could be a potential drug

  19. Prognostic significance of CD44s expression in resected non-small cell lung cancer

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    Ko Yoon

    2011-08-01

    Full Text Available Abstract Background CD44s is a cell adhesion molecule known to mediate cellular adhesion to the extracellular matrix, a prerequisite for tumor cell migration. CD44s plays an important role in invasion and metastasis of various cancers. In the present study, we sought to determine whether CD44s is involved in clinical outcomes of patients with resected non-small cell lung cancer (NSCLC. Methods Using immunohistochemical staining, we investigated CD44s protein expression using tissue array specimens from 159 patients with resected NSCLC (adenocarcinoma (AC; n = 82 and squamous cell carcinoma (SCC; n = 77. Additionally, the immunoreactivity of cyclooxygenase (COX-2 was also studied. The clinicopathological implications of these molecules were analyzed statistically. Results High CD44s expression was detected more frequently in NSCLC patients with SCC (66/72; 91.7% than in those with AC histology (P 0.001. Additionally, high CD44s expression was significant correlated with more advanced regional lymph node metastasis (P = 0.021. In multivariate analysis of survival in NSCLC patients with AC histology, significant predictors were lymph node metastasis status (P P = 0.046, and high CD44s expression (P = 0.014. For NSCLC patients with SCC histology, the significant predictor was a more advanced tumor stage (P = 0.015. No significant association was found between CD44s and clinical outcome (P = 0.311. Conclusions High CD44s expression was a negative prognostic marker with significance in patients with resected NSCLC, particularly those with AC histology, and was independent of tumor stage.

  20. Potential Diagnostic, Prognostic and Therapeutic Targets of MicroRNAs in Human Gastric Cancer

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    Ming-Ming Tsai

    2016-06-01

    Full Text Available Human gastric cancer (GC is characterized by a high incidence and mortality rate, largely because it is normally not identified until a relatively advanced stage owing to a lack of early diagnostic biomarkers. Gastroscopy with biopsy is the routine method for screening, and gastrectomy is the major therapeutic strategy for GC. However, in more than 30% of GC surgical patients, cancer has progressed too far for effective medical resection. Thus, useful biomarkers for early screening or detection of GC are essential for improving patients’ survival rate. MicroRNAs (miRNAs play an important role in tumorigenesis. They contribute to gastric carcinogenesis by altering the expression of oncogenes and tumor suppressors. Because of their stability in tissues, serum/plasma and other body fluids, miRNAs have been suggested as novel tumor biomarkers with suitable clinical potential. Recently, aberrantly expressed miRNAs have been identified and tested for clinical application in the management of GC. Aberrant miRNA expression profiles determined with miRNA microarrays, quantitative reverse transcription-polymerase chain reaction and next-generation sequencing approaches could be used to establish sample specificity and to identify tumor type. Here, we provide an up-to-date summary of tissue-based GC-associated miRNAs, describing their involvement and that of their downstream targets in tumorigenic and biological processes. We examine correlations among significant clinical parameters and prognostic indicators, and discuss recurrence monitoring and therapeutic options in GC. We also review plasma/serum-based, GC-associated, circulating miRNAs and their clinical applications, focusing especially on early diagnosis. By providing insights into the mechanisms of miRNA-related tumor progression, this review will hopefully aid in the identification of novel potential therapeutic targets.

  1. Non-coding RNAs Enabling Prognostic Stratification and Prediction of Therapeutic Response in Colorectal Cancer Patients.

    Science.gov (United States)

    Perakis, Samantha O; Thomas, Joseph E; Pichler, Martin

    2016-01-01

    Colorectal cancer (CRC) is a heterogeneous disease and current treatment options for patients are associated with a wide range of outcomes and tumor responses. Although the traditional TNM staging system continues to serve as a crucial tool for estimating CRC prognosis and for stratification of treatment choices and long-term survival, it remains limited as it relies on macroscopic features and cases of surgical resection, fails to incorporate new molecular data and information, and cannot perfectly predict the variety of outcomes and responses to treatment associated with tumors of the same stage. Although additional histopathologic features have recently been applied in order to better classify individual tumors, the future might incorporate the use of novel molecular and genetic markers in order to maximize therapeutic outcome and to provide accurate prognosis. Such novel biomarkers, in addition to individual patient tumor phenotyping and other validated genetic markers, could facilitate the prediction of risk of progression in CRC patients and help assess overall survival. Recent findings point to the emerging role of non-protein-coding regions of the genome in their contribution to the progression of cancer and tumor formation. Two major subclasses of non-coding RNAs (ncRNAs), microRNAs and long non-coding RNAs, are often dysregulated in CRC and have demonstrated their diagnostic and prognostic potential as biomarkers. These ncRNAs are promising molecular classifiers and could assist in the stratification of patients into appropriate risk groups to guide therapeutic decisions and their expression patterns could help determine prognosis and predict therapeutic options in CRC. PMID:27573901

  2. Prognostic significance of CD44s expression in resected non-small cell lung cancer

    International Nuclear Information System (INIS)

    CD44s is a cell adhesion molecule known to mediate cellular adhesion to the extracellular matrix, a prerequisite for tumor cell migration. CD44s plays an important role in invasion and metastasis of various cancers. In the present study, we sought to determine whether CD44s is involved in clinical outcomes of patients with resected non-small cell lung cancer (NSCLC). Using immunohistochemical staining, we investigated CD44s protein expression using tissue array specimens from 159 patients with resected NSCLC (adenocarcinoma (AC; n = 82) and squamous cell carcinoma (SCC; n = 77). Additionally, the immunoreactivity of cyclooxygenase (COX)-2 was also studied. The clinicopathological implications of these molecules were analyzed statistically. High CD44s expression was detected more frequently in NSCLC patients with SCC (66/72; 91.7%) than in those with AC histology (P <0.001). Additionally, high CD44s expression was significant correlated with more advanced regional lymph node metastasis (P = 0.021). In multivariate analysis of survival in NSCLC patients with AC histology, significant predictors were lymph node metastasis status (P < 0.001), high-grade tumor differentiation (P = 0.046), and high CD44s expression (P = 0.014). For NSCLC patients with SCC histology, the significant predictor was a more advanced tumor stage (P = 0.015). No significant association was found between CD44s and clinical outcome (P = 0.311). High CD44s expression was a negative prognostic marker with significance in patients with resected NSCLC, particularly those with AC histology, and was independent of tumor stage

  3. Prognostic factors for patients with esophageal cancer treated with radiation therapy in PCS. A preliminary study

    International Nuclear Information System (INIS)

    We investigated the prognostic factors, with special reference to age, for esophageal cancer patients, who did not receive surgery but were treated with radiation in the context of a Patterns of Care Study (PCS) in Japan. The fifth PCS database format employed in the United States was used to collect information on 455 esophageal cancer patients by external audit. The data of patients who had not received surgery (n=252) were further selected and divided into two age groups, patients 75 years old or older (n=90) and patients younger than 75 years (n=162). Cox's proportional hazards model was used for the statistical analysis, with crude survival as the endpoint. Variables tested were age; Karnofsky performance status (KPS); history of pulmonary disease, cardiovascular disease, and diabetes; AJCC stage; external dose; treatment period; combination with chemotherapy; utilization of brachytherapy, and stratification of institutions. Statistically significant prognostic factors for all patients in the non-surgery group were KPS (p=.0001), stage (p=.0001), and utilization of brachytherapy (p=.0102). For younger patients, KPS (p=.0001), stage (p=.0007), external dose (p=.0001), and utilization of brachytherapy (p=.0034) were significant, and for the elderly, stage (p=.0001) and external dose (p=.0006). Although this was a preliminary study, age was not a significant prognostic factor for esophageal cancer patients in the non-surgery group, and making the external dose more than 60 Gy appears to be effective for improving survival of elderly as well as younger patients. (author)

  4. Breast cancer with different prognostic characteristics developing in Danish women using hormone replacement therapy

    DEFF Research Database (Denmark)

    Stahlberg, Claudia; Pedersen, A T; Andersen, Zorana Jovanovic;

    2004-01-01

    The aim of this study is to investigate the risk of developing prognostic different types of breast cancer in women using hormone replacement therapy (HRT). A total of 10 874 postmenopausal Danish Nurses were followed since 1993. Incident breast cancer cases and histopathological information were...... retrieved through the National Danish registries. The follow-up ended on 31 December 1999. Breast cancer developed in 244 women, of whom 172 were invasive ductal carcinomas. Compared to never users, current users of HRT had an increased risk of a hormone receptor-positive breast cancer, but a neutral risk...... of receptor-negative breast cancer, relative risk (RR) 3.29 (95% confidence interval (CI): 2.27-4.77) and RR 0.99 (95% CI: 0.42-2.36), respectively (P for difference=0.013). The risk of being diagnosed with low histological malignancy grade was higher than high malignancy grade with RR 4.13 (95% CI...

  5. Podocalyxin as a Prognostic Marker in Gastric Cancer

    Science.gov (United States)

    Laitinen, Alli; Böckelman, Camilla; Hagström, Jaana; Kokkola, Arto; Fermér, Christian; Nilsson, Olle; Haglund, Caj

    2015-01-01

    Background Podocalyxin-like 1 (PODXL) is a cell-adhesion glycoprotein associated with aggressive tumor phenotype and poor prognosis in several forms of cancer. The aim of this study was to investigate PODXL expression in gastric cancer by use of two different antibodies. Methods By tumor-tissue microarrays and immunohistochemistry we evaluated PODXL expression in tumor specimens from 337 patients who underwent surgery for gastric adenocarcinoma at Helsinki University Hospital. We used two different antibodies: HPA2110, which is a polyclonal antibody and an in-house monoclonal antibody called HES9, to investigate the association of PODXL expression with clinicopathologic variables and patient survival. Results PODXL staining was positive by the polyclonal antibody in 153 (57.5%) cases and by the monoclonal antibody in 212 (76%). Polyclonal antibody expression was associated with intestinal cancer type (p<0.001). Monoclonal antibody staining was associated with age over 66 (p = 0.001), with intestinal cancer (p<0.001), and with small tumor size (≤ 5 cm; p = 0.024). Both antibodies were associated with high S-phase fraction (p = 0.022; p = 0.010), and high tumor proliferation index (Ki-67; p = 0.003; p = 0.001). PODXL positivity by the polyclonal antibody indicated reduced gastric-cancer-specific 5-year survival of 24.0% (95% CI 16.9–31.1), compared to 43.3% (95% CI 33.7–52.9) for patients with PODXL negativity (p = 0.001). The result remained significant in multivariable analysis (HR = 3.17; 95% CI 1.37–7.34, p = 0.007). Conclusion In gastric cancer, PODXL expression by the polyclonal antibody HPA2110 is an independent marker of poor prognosis. PMID:26674770

  6. Elevated Pretreatment Serum Concentration of YKL-40-An Independent Prognostic Biomarker for Poor Survival in Patients With Metastatic Nonsmall Cell Lung Cancer

    DEFF Research Database (Denmark)

    Thom, I.; Andritzky, B.; Schuch, G.;

    2010-01-01

    YKL-40 has not been established in non-small cell lung cancer (NSCLC). METHODS: Pretreatment serum levels of YKL-40 were determined in 189 patients with NSCLC (143 men and 46 women; median age, 62 years;, age range, 41-76 years). Twelve percent of patients had stage IIIB disease, and 88% had stage IV......BACKGROUND: The glycoprotein YKL-40 is synthesized both by cancer cells and by tumor-associated macrophages and plays a functional role in tumor progression. Consequently, high serum YKL-40 levels have been associated with a poor prognosis in patients with several cancer types. However, the role of...... was identified as a new, independent prognostic biomarker in patients with metastatic NSCLC and may help to determine the individual prognosis of these patients. Cancer 2010;116:4114-21. (C) 2010 American Cancer Society...

  7. Cyr61 is a potential prognostic marker for prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Naoki Terada; Prakash Kulkarni; Robert H Getzenberg

    2012-01-01

    Cysteine-rich angiogenic inducer 61 (Cyr61) is an extracellular matrix protein involved in the transduction of growth factor and hormone signaling that is frequently altered in expression in several types of cancers.In prostate cancer (PCa),Cyr61 is highly expressed in organ-confined disease.Further,Cyr61 expression levels are associated with a lower risk of disease recurrence,and can be quantitatively measured in the serum.Considered together,these results indicate that Cyr61 is a potential and clinically useful tissue,as well as serum-based biomarker for differentiating lethal and non-lethal PCa.

  8. Prognostic impact of vitamin B6 metabolism in lung cancer

    OpenAIRE

    Lorenzo Galluzzi; Ilio Vitale; Laura Senovilla; Ken André Olaussen; Guillaume Pinna; Tobias Eisenberg; Aïcha Goubar; Isabelle Martins; Judith Michels; Gueorgui Kratassiouk; Didac Carmona-Gutierrez; Marie Scoazec; Erika Vacchelli; Frederic Schlemmer; Oliver Kepp

    2012-01-01

    Patients with non-small cell lung cancer (NSCLC) are routinely treated with cytotoxic agents such as cisplatin. Through a genome-wide siRNA-based screen, we identified vitamin B6 metabolism as a central regulator of cisplatin responses in vitro and in vivo. By aggravating a bioenergetic catastrophe that involves the depletion of intracellular glutathione, vitamin B6 exacerbates cisplatin-mediated DNA damage, thus sensitizing a large panel of cancer cell lines to apoptosis. Moreover, vitamin B...

  9. Resting heart rate as a prognostic factor for mortality in patients with breast cancer.

    Science.gov (United States)

    Lee, Dong Hoon; Park, Seho; Lim, Sung Mook; Lee, Mi Kyung; Giovannucci, Edward L; Kim, Joo Heung; Kim, Seung Il; Jeon, Justin Y

    2016-09-01

    Although elevated resting heart rate (RHR) has been shown to be associated with mortality in the general population and patients with certain diseases, no study has examined this association in patients with breast cancer. A total of 4786 patients with stage I-III breast cancer were retrospectively selected from the Severance hospital breast cancer registry in Seoul, Korea. RHR was measured at baseline and the mean follow-up time for all patients was 5.0 ± 2.5 years. Hazard ratios (HRs) with 95 % confidence intervals (CIs) were calculated using Cox regression models. After adjustment for prognostic factors, patients in the highest quintile of RHR (≥85 beat per minute (bpm)) had a significantly higher risk of all-cause mortality (HR: 1.57; 95 %CI 1.05-2.35), breast cancer-specific mortality (HR: 1.69; 95 %CI 1.07-2.68), and cancer recurrence (HR: 1.49; 95 %CI 0.99-2.25), compared to those in the lowest quintile (≤67 bpm). Moreover, every 10 bpm increase in RHR was associated with 15, 22, and 6 % increased risk of all-cause mortality, breast cancer-specific mortality, and cancer recurrence, respectively. However, the association between RHR and cancer recurrence was not statistically significant (p = 0.26). Elevated RHR was associated with an increased risk of mortality in patients with breast cancer. The findings from this study suggest that RHR may be used as a prognostic factor for patients with breast cancer in clinical settings. PMID:27544225

  10. Favorable prognostic value of SOCS2 and IGF-I in breast cancer

    International Nuclear Information System (INIS)

    Suppressor of cytokine signaling (SOCS) proteins comprise a protein family, which has initially been described as STAT induced inhibitors of the Jak/Stat pathway. Recent in vivo and in vitro studies suggest that SOCS proteins are also implicated in cancer. The STAT5 induced IGF-I acts as an endocrine and para/autocrine growth and differentiation factor in mammary gland development. Whereas high levels of circulating IGF-I have been associated with increased cancer risk, the role of autocrine acting IGF-I is less clear. The present study is aimed to elucidate the clinicopathological features associated with SOCS1, SOCS2, SOCS3, CIS and IGF-I expression in breast cancer. We determined the mRNA expression levels of SOCS1, SOCS2, SOCS3, CIS and IGF-I in 89 primary breast cancers by reverse transcriptase PCR. SOCS2 protein expression was further evaluated by immuno-blot and immunohistochemistry. SOCS2 expression inversely correlated with histopathological grade and ER positive tumors exhibited higher SOCS2 levels. Patients with high SOCS2 expression lived significantly longer (108.7 vs. 77.7 months; P = 0.015) and high SOCS2 expression proved to be an independent predictor for good prognosis (HR = 0.45, 95% CI 0.23 – 0.91, P = 0.026). In analogy to SOCS2, high IGF-I expression was an independent predictor for good prognosis in the entire patient cohort. In the subgroup of patients with lymph-node negative disease, high IGF-I was a strong predictor for favorable outcome in terms of overall survival and relapse free survival (HR = 0.075, 95% CI 0.014 – 0.388, P = 0.002). This is the first report on the favorable prognostic value of high SOCS2 expression in primary mammary carcinomas. Furthermore a strong association of high IGF-I expression levels with good prognosis was observed especially in lymph-node negative patients. Our results suggest that high expression of the STAT5 target genes SOCS2 and IGF-I is a feature of differentiated and less malignant tumors

  11. Favorable prognostic value of SOCS2 and IGF-I in breast cancer

    Directory of Open Access Journals (Sweden)

    Daxenbichler Günter

    2007-07-01

    Full Text Available Abstract Background Suppressor of cytokine signaling (SOCS proteins comprise a protein family, which has initially been described as STAT induced inhibitors of the Jak/Stat pathway. Recent in vivo and in vitro studies suggest that SOCS proteins are also implicated in cancer. The STAT5 induced IGF-I acts as an endocrine and para/autocrine growth and differentiation factor in mammary gland development. Whereas high levels of circulating IGF-I have been associated with increased cancer risk, the role of autocrine acting IGF-I is less clear. The present study is aimed to elucidate the clinicopathological features associated with SOCS1, SOCS2, SOCS3, CIS and IGF-I expression in breast cancer. Methods We determined the mRNA expression levels of SOCS1, SOCS2, SOCS3, CIS and IGF-I in 89 primary breast cancers by reverse transcriptase PCR. SOCS2 protein expression was further evaluated by immuno-blot and immunohistochemistry. Results SOCS2 expression inversely correlated with histopathological grade and ER positive tumors exhibited higher SOCS2 levels. Patients with high SOCS2 expression lived significantly longer (108.7 vs. 77.7 months; P = 0.015 and high SOCS2 expression proved to be an independent predictor for good prognosis (HR = 0.45, 95% CI 0.23 – 0.91, P = 0.026. In analogy to SOCS2, high IGF-I expression was an independent predictor for good prognosis in the entire patient cohort. In the subgroup of patients with lymph-node negative disease, high IGF-I was a strong predictor for favorable outcome in terms of overall survival and relapse free survival (HR = 0.075, 95% CI 0.014 – 0.388, P = 0.002. Conclusion This is the first report on the favorable prognostic value of high SOCS2 expression in primary mammary carcinomas. Furthermore a strong association of high IGF-I expression levels with good prognosis was observed especially in lymph-node negative patients. Our results suggest that high expression of the STAT5 target genes SOCS2 and IGF

  12. Prognostic Value of MicroRNA-182 in Cancers: A Meta-Analysis

    OpenAIRE

    2015-01-01

    Objective. MicroRNA-182 (miR-182) exhibits altered expression in various cancers. The aim of this study was to investigate the predictive value of miR-182 expression for cancer patient survival. Methods. Eligible studies were identified through multiple search strategies, and the hazard ratios (HRs) for patient outcomes were extracted and estimated. A meta-analysis was performed to evaluate the prognostic value of miR-182. Results. In total, 14 studies were included. A high miR-182 expression...

  13. The prognostic value of tumour regression grade following neoadjuvant chemoradiation therapy for rectal cancer.

    LENUS (Irish Health Repository)

    Abdul-Jalil, K I

    2014-01-01

    To date, there is no uniform consensus on whether tumour regression grade (TRG) is predictive of outcome in rectal cancer. Furthermore, the lack of standardization of TRG grading is a major source of variability in published studies. The aim of this study was to evaluate the prognostic impact of TRG in a cohort of patients with locally advanced rectal cancer treated with neoadjuvant chemoradiation therapy (CRT). In addition to the Mandard TRG, we utilized four TRG systems modified from the Mandard TRG system and applied them to the cohort to assess which TRG system is most informative.

  14. Plasma levels of the MMP-9:TIMP-1 complex as prognostic biomarker in breast cancer

    DEFF Research Database (Denmark)

    Thorsen, Stine Buch; Christensen, Sarah Louise T; Würtz, Sidse Ørnbjerg;

    2013-01-01

    Worldwide more than one million women are annually diagnosed with breast cancer. A considerable fraction of these women receive systemic adjuvant therapy; however, some are cured by primary surgery and radiotherapy alone. Prognostic biomarkers guide stratification of patients into different risk...... groups and hence improve management of breast cancer patients. Plasma levels of Matrix Metalloproteinase-9 (MMP-9) and its natural inhibitor Tissue inhibitor of metalloproteinase-1 (TIMP-1) have previously been associated with poor patient outcome and resistance to certain forms of chemotherapy. To...

  15. FDG uptake in breast cancer: correlation with biological and clinical prognostic parameters

    International Nuclear Information System (INIS)

    The aim of this study was to evaluate the possible correlation between preoperative FDG-PET results in human breast cancer and the prognostic markers Ki-67, c-erb B2, p53, oestrogen/progesterone receptor status, axillary lymph node status, tumour size and tumour grading. Seventy-five female patients with breast cancer were included in this prospective study. Patient selection was independent of tumour size and the suspected clinical stage of disease. A high-resolution full-ring scanner (Siemens ECAT HR+) was used for PET imaging. The FDG uptake of breast tumours was calculated as the tumour to background ratio (TBR). In resected cancer tissue specimens, the proliferative fraction was evaluated by Ki-67 immunostaining. Additionally, immunostaining of the prognostic markers c-erb B2, p53, and progesterone and oestrogen receptors was performed. Haematoxylin and eosin-stained sections were used for tumour grading. Correlations between FDG uptake and prognostic markers were assumed to be significant at P<0.05 using the Mann-Whitney U test. In ductal breast cancer, mean TBR was 17.3 (median 7.7, range 1.6-122.7), while in lobular cancer it was 6.5 (median 3.7, range 1.4-22.7). Mean proliferative fraction (% Ki-67 positive tumour cells) was 15%±13.8% (median 10%, range 0%-60%). Twenty-three carcinomas showed <5% Ki-67 positive tumour cells. Statistical analysis indicated a positive correlation between FDG uptake and proliferative index in ductal breast cancer (P<0.0001, r=0.63). By contrast, there was no correlation between FDG uptake and c-erb B2 (P=0.79), p53 (P=0.92), tumour grading (P=0.09), oestrogen receptor status (P=0.41), progesterone receptor status (P=0.34), axillary lymph node status (P=0.90) and tumour size (P=0.3). It is concluded that FDG uptake is significantly higher in ductal breast cancer than in lobular cancer (P<0.05). FDG uptake correlates with proliferative activity assessed by Ki-67 immunostaining (P<0.05). A significant correlation with the other

  16. A fuzzy logic based-method for prognostic decision making in breast and prostate cancers.

    Science.gov (United States)

    Seker, Huseyin; Odetayo, Michael O; Petrovic, Dobrila; Naguib, Raouf N G

    2003-06-01

    Accurate and reliable decision making in oncological prognosis can help in the planning of suitable surgery and therapy, and generally, improve patient management through the different stages of the disease. In recent years, several prognostic markers have been used as indicators of disease progression in oncology. However, the rapid increase in the discovery of novel prognostic markers resulting from the development in medical technology, has dictated the need for developing reliable methods for extracting clinically significant markers where complex and nonlinear interactions between these markers naturally exist. The aim of this paper is to investigate the fuzzy k-nearest neighbor (FK-NN) classifier as a fuzzy logic method that provides a certainty degree for prognostic decision and assessment of the markers, and to compare it with: 1) logistic regression as a statistical method and 2) multilayer feedforward backpropagation neural networks an artificial neural-network tool, the latter two techniques having been widely used for oncological prognosis. In order to achieve this aim, breast and prostate cancer data sets are considered as benchmarks for this analysis. The overall results obtained indicate that the FK-NN-based method yields the highest predictive accuracy, and that it has produced a more reliable prognostic marker model than the statistical and artificial neural-network-based methods. PMID:12834167

  17. The Prognostic Value of Circulating Cell-Free DNA in Colorectal Cancer: A Meta-Analysis

    Science.gov (United States)

    Basnet, Shiva; Zhang, Zhen-yu; Liao, Wen-qiang; Li, Shu-heng; Li, Ping-shu; Ge, Hai-yan

    2016-01-01

    Background: Circulating cell-free DNA (cfDNA) is a promising candidate biomarker for detection, monitoring and survival prediction of colorectal cancer (CRC). However, its prognostic significance for patients with CRC remains controversial. To derive a precise estimation of the prognostic significance of cfDNA, a meta-analysis was performed. Methods: We made a systematic search in data base of the Science Citation Index Embase and Pubmed for studies reporting prognostic data of cfDNA in CRC patients. The data of cfDNA on recurrences-free survival (RFS) and overall survival (OS) were extracted and measured in hazard rates (HRs) and 95% confident intervals (CIs). Subgroup analyses were carried out as well. Finally, the meta-analysis is accompanied with nine studies including 19 subunits. Results: The pooled HRs with 95% CIs revealed strong associations between cfDNA and RFS (HR [95%CI]=2.78[2.08-3.72], I2=32.23%, n=7) along with OS (HR [95%CI]=3.03[2.51-3.66], I2=29.24%, n=12) in patients with CRC. Entire subgroup analyses indicated strong prognostic value of cfDNA irrespective tumor stage, study size, tumor markers, detection methods and marker origin. Conclusions: All the results exhibits that appearance of cfDNA in blood is an indicator for adverse RFS and OS in CRC patients. PMID:27326254

  18. Prognostic role ofthe ABO blood types inChinese patients withcuratively resected non-small cell lung cancer:a retrospective analysis of1601 cases ata single cancer center

    Institute of Scientific and Technical Information of China (English)

    NingLi; SiYuWang; MiaoXu; ChaoFengLi; WeiOu; BaoXiaoWang; SongLiangZhang; PengFeiXu; ChengYuan; QunAiHuang

    2015-01-01

    Background:A positive association between the ABO blood types and survival has been suggested in several malig‑nancies. The aim of this study was to assess the role of the ABO blood types in predicting the prognosis of Chinese patients with curatively resected non‑small cell lung cancer (NSCLC). Methods:We retrospectively analyzed 1601 consecutive Chinese patients who underwent curative surgery for NSCLC between January 1, 2005 and December 31, 2009. The relationship between the ABO blood types and survival was investigated. In addition, univariate and multivariate analyses were performed. Results:Group 1 (patients with the blood type O or B) had signiifcantly prolonged overall survival (OS) compared with group 2 (patients with the blood type A or AB), with a median OS of 74.9months versus 61.5months [hazard ratio (HR) 0.83; 95% conifdence interval (CI) 0.72–0.96;P=0.015]. Additionally, group 1 had signiifcantly longer dis‑ease‑free survival (DFS; HR 0.86; 95% CI 0.76–0.98;P=0.022) and locoregional relapse‑free survival (LRFS; HR 0.79; 95%CI 0.64–0.98;P=0.024) than group 2. The association was not signiifcantly modiifed by other risk factors for NSCLC, including smoking status, pathologic tumor‑node‑metastasis stage, pT category, pN category, and chemotherapy. Conclusions:There is an association between the ABO blood types and the survival of Chinese patients with resected NSCLC. Patients with the blood type O or B had signiifcantly prolonged OS, DFS, and LRFS compared with those with the blood type A or AB.

  19. Prognostic nomograms for predicting survival and distant metastases in locally advanced rectal cancers.

    Directory of Open Access Journals (Sweden)

    Junjie Peng

    Full Text Available To develop prognostic nomograms for predicting outcomes in patients with locally advanced rectal cancers who do not receive preoperative treatment.A total of 883 patients with stage II-III rectal cancers were retrospectively collected from a single institution. Survival analyses were performed to assess each variable for overall survival (OS, local recurrence (LR and distant metastases (DM. Cox models were performed to develop a predictive model for each endpoint. The performance of model prediction was validated by cross validation and on an independent group of patients.The 5-year LR, DM and OS rates were 22.3%, 32.7% and 63.8%, respectively. Two prognostic nomograms were successfully developed to predict 5-year OS and DM-free survival rates, with c-index of 0.70 (95% CI = [0.66, 0.73] and 0.68 (95% CI = [0.64, 0.72] on the original dataset, and 0.76 (95% CI = [0.67, 0.86] and 0.73 (95% CI = [0.63, 0.83] on the validation dataset, respectively. Factors in our models included age, gender, carcinoembryonic antigen value, tumor location, T stage, N stage, metastatic lymph nodes ratio, adjuvant chemotherapy and chemoradiotherapy. Predicted by our nomogram, substantial variability in terms of 5-year OS and DM-free survival was observed within each TNM stage category.The prognostic nomograms integrated demographic and clinicopathological factors to account for tumor and patient heterogeneity, and thereby provided a more individualized outcome prognostication. Our individualized prediction nomograms could help patients with preoperatively under-staged rectal cancer about their postoperative treatment strategies and follow-up protocols.

  20. Low expression of aldehyde deyhdrogenase 1A1 (ALDH1A1) is a prognostic marker for poor survival in pancreatic cancer

    International Nuclear Information System (INIS)

    Aldehyde deyhdrogenase 1 (ALDH1) has been characterised as a cancer stem cell marker in different types of tumours. Additionally, it plays a pivotal role in gene regulation and endows tumour cells with augmented chemoresistance. Recently, ALDH1A1 has been described as a prognostic marker in a pancreatic cancer tissue microarray. The aim of this study was to reevaluate the expression of ALDH1A1 as a prognostic marker on whole-mount tissue sections. Real-time-quantitative-PCR (qRT-PCR) and Western blotting were used to evaluate the expression profile of ALDH1A1 in seven pancreatic cancer cell lines and one non-malignant pancreatic cell line. Immunostaining against ALDH1A1 and Ki-67 was performed on paraffin-embedded samples from 97 patients with pancreatic cancer. The immunohistochemical results were correlated to histopathological and clinical data. qRT-PCR and Western blotting revealed a different expression pattern of ALDH1A1 in different malignant and non-malignant pancreatic cell lines. Immunohistochemical analysis demonstrated that ALDH1A1 was confined to the cellular cytoplasm and occurred in 72 cases (74%), whereas it was negative in 25 cases (26%). High expression of ALDH1A1 was significantly correlated to an increased proliferation rate (Spearman correlation, p = 0.01). Univariate and multivariate analyses showed that decreased expression of ALDH1A1 is an independent adverse prognostic factor for overall survival. Immunonhistochemical analysis on whole-mount tissue slides revealed that ALDH1A1 is more abundantly expressed in pancreatic cancer than initially reported by a tissue microarray analysis. Moreover, high expression of ALDH1A1 correlated significantly with the proliferation of tumour cells. Intriguingly, this study is the first which identifies low expression of ALDH1A1 as an independent adverse prognostic marker for overall survival in pancreatic cancer

  1. Prognostic Importance of Bcl-2 Expression in Colon Cancer

    OpenAIRE

    Arsenal Alikanoðlu

    2012-01-01

    Aim: TNM classification, that had been established according to pathologic and anatomic characteristics of the lesion , is the most important factor in decision of adjuvant therapy in colon cancer. Despite curative resection, recurrence can ocur with a rate of 20-30% in early stage disease. Therefore efficieny of TNM classification is controversial. In recent years ,significance of molecular characteristics of the tumors besides their anatomic and pathologic characteristics in determining the...

  2. The BRCA1/BRCA2/Rad51 complex is a prognostic and predictive factor in early breast cancer

    International Nuclear Information System (INIS)

    Background and purpose: The breast cancer susceptibility genes BRCA1 and BRCA2 interact with Rad51, one of the central components in the homologous recombination repair pathway. This study evaluates the prognostic and predictive role of BRCA1, BRCA2 and Rad51, individually and as a complex, in breast cancer. Materials and methods: Expression of BRCA1, BRCA2 and Rad51 was investigated using immunohistochemistry in tumours from 224 women with early breast cancer, who were randomised to receive postoperative radiotherapy or adjuvant chemotherapy (CMF). Results: Fifty-three percent (112/212) of the tumours had reduced expression of the BRCA1/BRCA2/Rad51 complex. Low expression correlated to high histologic grade (p = 0.05). Patients with low expression of the complex developed significantly more local recurrences as compared to patients with high expression (RR = 3.20, 95% CI 1.48-6.88, p = 0.003). Expression of the BRCA1/BRCA2/Rad51 complex was an independent prognostic factor in multivariate analysis (p = 0.03). Patients with low expression of the complex responded well to radiotherapy (RR = 0.31, 95% CI 0.14-0.70, p = 0.005), whereas patients with high expression had few local recurrences and no additional benefit from radiotherapy (RR = 1.08, 95% CI 0.40-2.90, p = 0.88). Conclusions: Low expression of the BRCA1/BRCA2/Rad51 complex is a marker of poor prognosis, but predicts good response to radiotherapy in patients with early breast cancer

  3. Rectal cancer staging: focus on the prognostic significance of the findings described by high-resolution magnetic resonance imaging.

    Science.gov (United States)

    Dieguez, Adriana

    2013-01-01

    High-resolution (HR) magnetic resonance imaging (MRI) has become an indispensable tool for multidisciplinary teams (MDTs) addressing rectal cancer. It provides anatomic information for surgical planning and allows patients to be stratified into different groups according to the risk of local and distant recurrence. One of the objectives of the MDT is the preoperative identification of high-risk patients who will benefit from neoadjuvant treatment. For this reason, the correct evaluation of the circumferential resection margin (CRM), the depth of tumor spread beyond the muscularis propria, extramural vascular invasion and nodal status is of the utmost importance. Low rectal tumors represent a special challenge for the MDT, because decisions seek a balance between oncologic safety, in the pursuit of free resection margins, and the patient's quality of life, in order to preserve sphincter function. At present, the exchange of information between the different specialties involved in dealing with patients with rectal cancer can rank the contribution of colleagues, auditing their work and incorporating knowledge that will lead to a better understanding of the pathology. Thus, beyond the anatomic description of the images, the radiologist's role in the MDT makes it necessary to know the prognostic value of the findings that we describe, in terms of recurrence and survival, because these findings affect decision making and, therefore, the patients' life. In this review, the usefulness of HR MRI in the initial staging of rectal cancer and in the evaluation of neoadjuvant treatment, with a focus on the prognostic value of the findings, is described as well as the contribution of HR MRI in assessing patients with suspected or confirmed recurrence of rectal cancer. PMID:23876415

  4. Prognostic Significance of Mucin Antigen MUC1 in Various Human Epithelial Cancers: A Meta-Analysis.

    Science.gov (United States)

    Xu, Feng; Liu, Fuquan; Zhao, Hongwei; An, Guangyu; Feng, Guosheng

    2015-12-01

    Accumulating evidence indicates that mucin antigen MUC1 plays a fundamental role in the initiation and progression of several types of epithelial carcinomas. However, whether the expression of MUC1 on tumor cells is associated with patients' survival remains controversial. Medline/PubMed, EMBASE, the Cochrane Library, Chinese National Knowledge Infrastructure (CNKI) databases, and Grey literature were searched up to 15 August 2015 for eligible studies of the association between the MUC1 expression and overall survival (OS) in various epithelial cancers. The hazard ratio (HR) and its 95% confidence interval (CI) were calculated from the included studies. Moreover, the odds ratio (OR) was also extracted to evaluate the association between the clinicopathological parameters of participants and MUC1 expression. A total of 3425 patients covering 23 studies were included in the analysis. The pooled results showed that positive MUC1 staining was a negative predictor of OS (HRFEM = 1.98,95% CIFEM: 1.76-2.22, PFEM = 0.479; HRREM = 2.16,95% CIREM: 1.58-2.94, PREM = 0.355) in various epithelial carcinomas. Subgroup analysis revealed that the increased MUC1 expression was significantly associated with poor OS in patients with gastric cancer (HRFEM = 2.12, 95%CIFEM: 1.75-2.57, PFEM = 0.359; HRREM = 1.89, 95% CIREM: 1.05-3.41, PREM = 0.238), colorectal cancer (HRFEM = 1.73, 95%CIFEM: 1.41-2.13, PFEM = 0.048; HRREM = 2.00,95% CIREM: 1.46-2.73, PREM = 0.019), cholangiocarcinoma (HRFEM = 2.52, 95% CIFEM: 1.42-4.49, PFEM = 0.252; HRREM = 2.34, 95% CIREM: 1.30-4.22, PREM = 0.244), and nonsmall cell lung cancer (NSCLC) (HRFEM = 2.14, 95% CIFEM: 1.46-3.14, PFEM = 0.591; HRREM = 2.81, 95% CIREM: 1.40-5.64, PREM = 0.280). In addition, MUC1 overexpression was more likely to be found in colorectal cancer patients with an advanced tumor node metastasis stage (ORREM = 1.55, 95% CIREM: 1.06-2.27; PREM = 0

  5. PTIP associated protein 1, PA1, is an independent prognostic factor for lymphnode negative breast cancer.

    Directory of Open Access Journals (Sweden)

    Takashi Takeshita

    Full Text Available Pax transactivation domain interacting protein (PTIP associated protein 1, PA1, was a newly found protein participating in the modulation of transactivity of nuclear receptor super family members such as estrogen receptor (ER, androgen receptor (AR and glucocorticoid receptor (GR. Breast cancer is one of the most life threatening diseases for women and has tight association with estrogen and ER. This study was performed to understand the function of PA1 in breast cancer. The expression of PA1 had been evaluated in a total of 344 primary invasive breast cancer samples and examined the relationship with clinical output, relapse free survival (RFS, breast cancer-specific survival (BCSS. PA1 expression was observed in both nucleus and cytoplasm, however, appeared mainly in nuclear. PA1 nuclear expression was correlated with postmenopausal (P = 0.0097, smaller tumor size (P = 0.0025, negative Ki67 (P = 0.02, positive AR (P = 0.049 and positive ERβ (P = 0.0020. Kaplan-Meier analysis demonstrated PA1 nuclear positive cases seemed to have a longer survival than negative ones for RFS (P = 0.023 but not for BCSS (P = 0.23. In the Cox hazards model, PA1 nuclear protein expression proved to be a significant prognostic univariate parameter for RFS (P = 0.03, but not for BCSS (P = 0.20. In addition, for those patients without lymphnode metastasis PA1 was found to be an independent prognostic factor for RFS (P = 0.025, which was verified by univariate and multivariate analyses. These investigations suggested PA1 expression could be a potential prognostic indicator for RFS in breast cancer.

  6. Prognostic value of the lymph node ratio in stage Ⅲcolorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Jing-Qing Ren; Jian-Wei Liu; Zhi-Tang Chen; Shao-Jie Liu; Shi-Jie Huang; Yong Huang; Jing-Song Hong

    2012-01-01

    The nodal stage of colorectal cancer is based on the number of positive nodes.It is inevitably affected by the number of removed lymph nodes,but lymph node ratio can be unaffected.We investigated the value of lymph node ratio in stage Ⅲ colorectal cancer in this study.The clinicopathologic factors and follow-up data of 145 cases of stage Ⅲ colorectal cancer between January 1998 and December 2008 were analyzed retrospectively.The Pearson and Spearman correlation analyses were used to determine the correlation coefficient,the Kaplan-Meier method was used to analyze survival,and the Cox proportional hazard regression model was used for multivariate analysis in forward stepwise regression.We found that lymph node ratio was not correlated with the number of removed lymph nodes (r =-0.154,P =0.065),but it was positively correlated with the number of positive lymph nodes (r =0.739,P <0.001) and N stage (r =0.695,P < 0.001),Kaplan-Meier survival analysis revealed that tumor configuration,intestinal obstruction,serum carcinoembryonic antigen (CEA) concentration,T stage,N stage,and lymph node ratio were associated with disease-free survival of patients with stage Ⅲ colorectal cancer (P < 0.05).Multivariate analysis showed that serum CEA concentration,T stage,and lymph node ratio were prognostic factors for disease-free survival (P < 0.05),whereas N stage failed to achieve significance (P =0.664).We confirmed that lymph node ratio was a prognostic factor in stage Ⅲ colorectal cancer and had a better prognostic value than did N stage.

  7. Prognostic factors for survival of women with unstable spinal bone metastases from breast cancer

    International Nuclear Information System (INIS)

    Bone metastases are an important clinical issue in women with breast cancer. Particularly, unstable spinal bone metastases (SBM) are a major cause of severe morbidity and reduced quality of life (QoL) due to frequent immobilization. Radiotherapy (RT) is the major treatment modality and is capable of promoting re-ossification and improving stability. Since local therapy response is excellent, survival of these patients with unstable SBM is of high clinical importance. We therefore conducted this analysis to assess survival and to determine prognostic factors for bone survival (BS) in women with breast cancer and unstable SBM. A total population of 92 women with unstable SBM from breast cancer who were treated with RT at our department between January 2000 and January 2012 was retrospectively investigated. We calculated overall survival (OS) and BS (time between first diagnosis of bone metastases until death) with the Kaplan-Meier method and assessed prognostic factors for BS with a Cox regression model. Mean age at first diagnosis of breast cancer was 60.8 years ± SD 12.4 years. OS after 1, 2 and 5 years was 84.8, 66.3 and 50 %, respectively. BS after 1, 2 and 5 years was 62.0, 33.7 and 12 %, respectively. An age > 50 years (p < .001; HR 1.036 [CI 1.015–1.057]), the presence of a single bone metastasis (p = .002; HR 0.469 [CI 0.292–0.753]) and triple negative phenotype (p < .001; HR 1.068 [CI 0.933–1.125]) were identified as independent prognostic factors for BS. Our analysis demonstrated a short survival of women with breast cancer and unstable SBM. Age, presence of a solitary SBM and triple-negative phenotype correlated with survival. Our results may have an impact on therapeutic decisions in the future and offer a rationale for future prospective investigations

  8. MiR-378 is an independent prognostic factor and inhibits cell growth and invasion in colorectal cancer

    International Nuclear Information System (INIS)

    MicroRNAs(miRNAs) are small non-coding RNAs that participate in a variety of biologic processes, and dysregulation of miRNA is always associated with cancer development and progression. Aberrant expression of miR-378 has been found in some types of cancer. However, effects and potential mechanisms of miR-378 in colorectal cancer (CRC) have not been explored. Quantitative RT-PCR was performed to evaluate miR-378 levels in CRC cell lines and 84 pairs of CRC cancer and normal adjacent mucosa. Kaplan–Meier and Cox proportional regression analyses were utilized to determine the association of miR-378 expression with survival of patients. MTT and invasion assays were used to determine the role of miR-378 in regulation of CRC cancer cell growth and invasion, respectively. Tumor growth was assessed by subcutaneous inoculation of cells into BALB/c nude mice. Luciferase assay was performed to assess miR-378 binding to vimentin gene. In this study, we confirmed that miR-378 significantly down-regulated in CRC cancer tissues and cell lines. Moreover, patients with low miR-378 expression had significantly poorer overall survival, and miR-378 expression was an independent prognostic factor in CRC. Over-expression of miR-378 inhibited SW620 cell growth and invasion, and resulted in down-regulation of vimentin expression. However, miR-378 knock-down promoted these processes and enhanced the expression of vimentin. In addition, we further identified vimentin as the functional downstream target of miR-378 by directly targeting the 3′-UTR of vimentin. In conclusion, miR-378 may function as a tumor suppressor and plays an important role in inhibiting tumor growth and invasion. Our present results implicate the potential effects of miR-378 on prognosis and treatment of CRC cancer

  9. Prognostic impact of immunohistochemical expression of CK7 and CK20 in curatively resected ampulla of Vater cancer

    OpenAIRE

    Yun, Sung Pil; Seo, Hyung Il

    2015-01-01

    Background In the consideration of ampullary adenocarcinoma, T stage, lymph node metastases, perineural invasion, tumor differentiation, pancraticobiliary type, and lymph node ratio are considered prognostic factors. The objectives of this study were to investigate surgical outcomes and the clinicopathological predictors affecting survival and recurrence, and to examine the prognostic roles of histopathological subtype and immunohistochemical markers. Methods From April 2006 to September 2012...

  10. ExSurv: A Web Resource for Prognostic Analyses of Exons Across Human Cancers Using Clinical Transcriptomes.

    Science.gov (United States)

    Hashemikhabir, Seyedsasan; Budak, Gungor; Janga, Sarath Chandra

    2016-01-01

    Survival analysis in biomedical sciences is generally performed by correlating the levels of cellular components with patients' clinical features as a common practice in prognostic biomarker discovery. While the common and primary focus of such analysis in cancer genomics so far has been to identify the potential prognostic genes, alternative splicing - a posttranscriptional regulatory mechanism that affects the functional form of a protein due to inclusion or exclusion of individual exons giving rise to alternative protein products, has increasingly gained attention due to the prevalence of splicing aberrations in cancer transcriptomes. Hence, uncovering the potential prognostic exons can not only help in rationally designing exon-specific therapeutics but also increase specificity toward more personalized treatment options. To address this gap and to provide a platform for rational identification of prognostic exons from cancer transcriptomes, we developed ExSurv (https://exsurv.soic.iupui.edu), a web-based platform for predicting the survival contribution of all annotated exons in the human genome using RNA sequencing-based expression profiles for cancer samples from four cancer types available from The Cancer Genome Atlas. ExSurv enables users to search for a gene of interest and shows survival probabilities for all the exons associated with a gene and found to be significant at the chosen threshold. ExSurv also includes raw expression values across the cancer cohort as well as the survival plots for prognostic exons. Our analysis of the resulting prognostic exons across four cancer types revealed that most of the survival-associated exons are unique to a cancer type with few processes such as cell adhesion, carboxylic, fatty acid metabolism, and regulation of T-cell signaling common across cancer types, possibly suggesting significant differences in the posttranscriptional regulatory pathways contributing to prognosis. PMID:27528797

  11. ExSurv: A Web Resource for Prognostic Analyses of Exons Across Human Cancers Using Clinical Transcriptomes

    Science.gov (United States)

    Hashemikhabir, Seyedsasan; Budak, Gungor; Janga, Sarath Chandra

    2016-01-01

    Survival analysis in biomedical sciences is generally performed by correlating the levels of cellular components with patients’ clinical features as a common practice in prognostic biomarker discovery. While the common and primary focus of such analysis in cancer genomics so far has been to identify the potential prognostic genes, alternative splicing – a posttranscriptional regulatory mechanism that affects the functional form of a protein due to inclusion or exclusion of individual exons giving rise to alternative protein products, has increasingly gained attention due to the prevalence of splicing aberrations in cancer transcriptomes. Hence, uncovering the potential prognostic exons can not only help in rationally designing exon-specific therapeutics but also increase specificity toward more personalized treatment options. To address this gap and to provide a platform for rational identification of prognostic exons from cancer transcriptomes, we developed ExSurv (https://exsurv.soic.iupui.edu), a web-based platform for predicting the survival contribution of all annotated exons in the human genome using RNA sequencing-based expression profiles for cancer samples from four cancer types available from The Cancer Genome Atlas. ExSurv enables users to search for a gene of interest and shows survival probabilities for all the exons associated with a gene and found to be significant at the chosen threshold. ExSurv also includes raw expression values across the cancer cohort as well as the survival plots for prognostic exons. Our analysis of the resulting prognostic exons across four cancer types revealed that most of the survival-associated exons are unique to a cancer type with few processes such as cell adhesion, carboxylic, fatty acid metabolism, and regulation of T-cell signaling common across cancer types, possibly suggesting significant differences in the posttranscriptional regulatory pathways contributing to prognosis. PMID:27528797

  12. Molecular biomarkers of colorectal cancer: prognostic and predictive tools for clinical practice

    Institute of Scientific and Technical Information of China (English)

    Wei-qin JIANG; Fang-fang FU; Yang-xia LI; Wei-bin WANG; Hao-hao WANG; Hai-ping JIANG; Li-song TENG

    2012-01-01

    Colorectal cancer remains one of the most common types of cancer and leading causes of cancer death worldwide.Although we have made steady progress in chemotherapy and targeted therapy,evidence suggests that the majority of patients undergoing drug therapy experience severe,debilitating,and even lethal adverse drug events which considerably outweigh the benefits.The identification of suitable biomarkers will allow clinicians to deliver the most appropriate drugs to specific patients and spare them ineffective and expensive treatments.Prognostic and predictive biomarkers have been the subjects of many published papers,but few have been widely incorporated into clinical practice.Here,we want to review recent biomarker data related to colorectal cancer,which may have been ready for clinical use.

  13. Clinical outcomes of adjuvant radiation therapy and prognostic factors in early stage uterine cervical cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyun Ju; Rhee, Woo Joong; Choi, Seo Hee; Kim, Gwi Eon; Kim, Yong Bae [Dept. of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul (Korea, Republic of); Nam, EunJi; Kim, Sang Wun; Kim, Sung Hoon [Dept. of Radiation Oncology, Obstetrics and Gynecology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2015-06-15

    To evaluate the outcomes of adjuvant radiotherapy (RT) and to analyze prognostic factors of survival in the International Federation of Gynecology and Obstetrics (FIGO) IB-IIA uterine cervical cancer. We retrospectively reviewed the medical records of 148 patients with FIGO IB-IIA uterine cervical cancer who underwent surgery followed by adjuvant RT at the Yonsei Cancer Center between June 1997 and December 2011. Adjuvant radiotherapy was delivered to the whole pelvis or an extended field with or without brachytherapy. Among all patients, 57 (38.5%) received adjuvant chemotherapy either concurrently or sequentially. To analyze prognostic factors, we assessed clinicopathologic variables and metabolic parameters measured on preoperative {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). To evaluate the predictive performance of metabolic parameters, receiver operating characteristic curve analysis was used. Overall survival (OS) and disease-free survival (DFS) were analyzed by the Kaplan-Meier method. The median follow-up period was 63.2 months (range, 2.7 to 206.8 months). Locoregional recurrence alone occurred in 6 patients, while distant metastasis was present in 16 patients, including 2 patients with simultaneous regional failure. The 5-year and 10-year OSs were 87.0% and 85.4%, respectively. The 5-year and 10-year DFSs were 83.8% and 82.5%, respectively. In multivariate analysis, pathologic type and tumor size were shown to be significant prognostic factors associated with both DFS and OS. In subset analysis of 40 patients who underwent preoperative PET/CT, total lesion glycolysis was shown to be the most significant prognostic factor among the clinicopathologic variables and metabolic parameters for DFS. Our results demonstrated that adjuvant RT following hysterectomy effectively improves local control. From the subset analysis of preoperative PET/CT, we can consider that metabolic parameters may hold prognostic

  14. The prognostic significance of apoptosis-related biological markers in Chinese gastric cancer patients.

    Directory of Open Access Journals (Sweden)

    Xiaowen Liu

    Full Text Available BACKGROUND AND OBJECTIVE: The prognosis varied among the patients with the same stage, therefore there was a need for new prognostic and predictive factors. The aim of this study was to evaluate the relationship of apoptosis-related biological markers such as p53, bcl-2, bax, and c-myc, and clinicopathological features and their prognostic value. METHODS: From 1996 to 2007, 4426 patients had undergone curative D2 gastrectomy for gastric cancer at Fudan University Shanghai Cancer Center. Among 501 patients, the expression levels of p53, bcl-2, bax, and c-myc were examined by immunohistochemistry. The prognostic value of biological markers and the correlation between biological markers and other clinicopathological factors were investigated. RESULTS: There were 339 males and 162 females with a mean age of 57. The percentages of positive expression of p53, bcl-2, bax, and c-myc were 65%, 22%, 43%, and 58%, respectively. There was a strong correlation between p53, bax, and c-myc expression (P=0.00. There was significant association between bcl-2, and bax expression (P<0.05. p53 expression correlated with histological grade (P=0.01; bcl-2 expression with pathological stage (P=0.00; bax expression with male (P=0.02, histological grade (P=0.01, Borrmann type (P=0.01, tumor location (P=0.00, lymph node metastasis (P=0.03, and pathological stage (P=0.03; c-myc expression with Borrmann type (P=0.00. bcl-2 expression was related with good survival in univariate analysis (P=0.01. Multivariate analysis showed that bcl-2 expression and pathological stage were defined as independent prognostic factors. There were significant differences of overall 5-year survival rates according to bcl-2 expression or not in stage IIB (P=0.03. CONCLUSION: The expression of bcl-2 was an independent prognostic factor for patients with gastric cancer; it might be a candidate for the gastric cancer staging system.

  15. Serum Ferritin as a Prognostic Biomarker for Survival in Relapsed or Refractory Metastatic Colorectal Cancer

    Science.gov (United States)

    Lee, Sookyung; Song, Anna; Eo, Wankyu

    2016-01-01

    Background: This study investigated the prognostic impact of serum ferritin for survival in patients with relapsed or refractory metastatic colorectal cancer (mCRC). Methods: This retrospective cohort study reviewed clinicopathological characteristics and laboratory biomarkers in 120 mCRC patients being treated with Korean Medicine (KM). The overall survival (OS) of patients was calculated using the Kaplan-Meier method, and statistical significance was assessed using the log-rank test. Univariate and multivariate analyses of Cox proportional hazards regression were used to evaluate the prognostic impact for survival in relapsed or refractory mCRC patients. Results: Of the patients, 62.5% had liver metastases, 74.1% underwent greater than second-line chemotherapy, and 80.8% underwent surgery. Median OS was 7.6 months for all patients after the initiation of KM treatment, which was begun 13.7 months, on average, after mCRC diagnosis. Concerning prognostic factors such as the presence of liver metastasis (p = 0.024), high carcinoembryonic antigen level (CEA > 5 ng/mL, p = 0.044), elevated C-reactive protein (CRP ≥ 10.0 mg/L, p = 0.000), high absolute monocyte count (AMC > 413.3 cells/μL, p = 0.034), elevated serum ferritin (ferritin ≥ 150 ng/mL, p = 0.002), low hemoglobin level (Hb 5 ng/mL; HR 2.040, 95% CI 1.203 - 3.460, p = 0.008), and serum ferritin (ferritin ≥ 150 ng/mL; HR 1.763, 95% CI 1.169 - 2.660, p = 0.007) were independent prognostic biomarkers of survival in mCRC patients. Conclusions: These results indicate that serum ferritin acts as an independent prognostic biomarker for survival in relapsed or refractory mCRC patients.

  16. Tumour-associated endothelial-FAK correlated with molecular sub-type and prognostic factors in invasive breast cancer

    International Nuclear Information System (INIS)

    Breast cancer is a heterogeneous disease that can be classified into one of 4 main molecular sub-types: luminal A, luminal B, Her2 over-expressing and basal-like (BL). These tumour sub-types require different treatments and have different risks of disease progression. BL cancers can be considered a sub-group of Triple negative (TN) cancers since they lack estrogen (ER), progesterone (PR) and Her2 expression. No targeted treatment currently exists for TN/BL cancers. Thus it is important to identify potential therapeutic targets and describe their relationship with established prognostic factors. Focal adhesion kinase (FAK) is upregulated in several human cancers and also plays a functional role in tumour angiogenesis. However, the association between breast cancer sub-types and tumour endothelial-FAK expression is unknown. Using immunofluorescence, we quantified FAK expression in tumour endothelial and tumour cell compartments in 149 invasive breast carcinomas and correlated expression with clinical, pathological and molecular parameters. Low endothelial-FAK expression was independently associated with luminal A tumours at univariate (p < 0.001) and multivariate (p = 0.001) analysis. There was a positive correlation between FAK expression in the vascular and tumour cell compartments (Spearman’s correlation co-efficient = 0.394, p < 0.001). Additionally, endothelial and tumour cell FAK expression were significantly increased in TN tumours (p = 0.043 and p = 0.033 respectively), in tumours with negative ER and PR status, and in high grade tumours at univariate analysis. Our findings establish a relationship between endothelial-FAK expression levels and the molecular sub-type of invasive breast cancer, and suggest that endothelial-FAK expression is potentially more clinically relevant than tumour cell FAK expression in breast cancer

  17. The Role of chemokine receptor CXCR4 in breast cancer metastasis

    OpenAIRE

    Mukherjee, Debarati; Zhao, Jihe

    2013-01-01

    Breast cancer is one of the leading causes of cancer related deaths worldwide. Breast cancer-related mortality is associated with the development of metastatic potential of primary tumor lesions. The chemokine receptor CXCR4 has been found to be a prognostic marker in various types of cancer, including breast cancer. Recent advances in the field of cancer biology has pointed to the critical role that CXCR4 receptor and its ligand CXCL12 play in the metastasis of various types of cancer, inclu...

  18. Prognostic value of Chinese race in nasopharyngeal cancer

    International Nuclear Information System (INIS)

    Purpose: Nasopharyngeal carcinoma is rare in the United States and common in southern China. Evaluating American patients treated using a uniform technique and staged with CT scanning, we determined whether Chinese and non-Chinese patients differ in presentation and outcome. Methods and Materials: Between 1979 and 1996, 172 patients treated at Massachusetts General Hospital received primary radiotherapy with curative intent for nasopharyngeal carcinoma. Forty-one patients (24%) were of Chinese descent, and 41% of cancers were classified as having lymphoepithelioma histologic features. Most patients received twice-daily radiotherapy and a brachytherapy boost, receiving a median dose of 72 Gy to the nasopharynx. Results: At the initial presentation, the Chinese patients were significantly younger, less likely to smoke, more likely to have Stage IV disease, and more likely to have cancer with lymphoepithelioma histologic features. After controlling for stage, age, histologic type, and treatment variables, Chinese patients were significantly more likely to develop distant metastases (p<0.05). Although Chinese race does not predict for local control or overall survival, a younger age, continued tobacco use, total radiation dose, and lymphoepithelioma histologic features do. Conclusion: In a large retrospective analysis of nasopharyngeal carcinoma, Chinese and non-Chinese patients differed significantly in presentation--age, stage, and histologic features--and outcome. We suggest as an explanation differences in intrinsic tumor biology rather than differences in treatment techniques or staging systems. Additional trials in endemic countries are needed to confirm the optimal treatment of Chinese and Chinese-American patients

  19. Gene Expression Profiles as Prognostic Marker in Women with Ovarian Cancer

    DEFF Research Database (Denmark)

    Jochumsen, Kirsten Marie; Tan, Qihua; Høgdall, EV;

    2009-01-01

    toward investigations for more individualized therapies and the use of gene expression profiles in the clinical practice. RNA from tumor tissue from 43 Danish patients with serous epithelial ovarian carcinoma (11 International Federation of Gynecology and Obstetrics [FIGO] stage I/II, 32 FIGO stage III...... disease. Furthermore, its ability to classify in an external validation set was demonstrated. The identified 14-gene prognostic profile was able to predict survival (short- vs long-term survival) with a strength that is better than any other prognostic factor in epithelial ovarian cancer including FIGO......The purpose was to find a gene expression profile that could distinguish short-term from long-term survivors in our collection of serous epithelial ovarian carcinomas. Furthermore, it should be able to stratify in an external validation set. Such a classifier profile will take us a step forward...

  20. Gene expression profiles as prognostic markers in women with ovarian cancer

    DEFF Research Database (Denmark)

    Jochumsen, Kirsten M; Tan, Qihua; Høgdall, Estrid V;

    2009-01-01

    toward investigations for more individualized therapies and the use of gene expression profiles in the clinical practice. RNA from tumor tissue from 43 Danish patients with serous epithelial ovarian carcinoma (11 International Federation of Gynecology and Obstetrics [FIGO] stage I/II, 32 FIGO stage III...... disease. Furthermore, its ability to classify in an external validation set was demonstrated. The identified 14-gene prognostic profile was able to predict survival (short- vs long-term survival) with a strength that is better than any other prognostic factor in epithelial ovarian cancer including FIGO......The purpose was to find a gene expression profile that could distinguish short-term from long-term survivors in our collection of serous epithelial ovarian carcinomas. Furthermore, it should be able to stratify in an external validation set. Such a classifier profile will take us a step forward...

  1. Prognostic and predictive value of liver volume on colorectal cancer patients with unresectable liver metastases

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jun Su; Park, Hee Chul; Choi, Doo Ho; Park, Won; Yu, Jeong Il; Park, Young Suk; Kang, Won Ki; Park, Joon Oh [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2014-06-15

    To determine the prognostic and predictive value of liver volume in colorectal cancer patients with unresectable liver metastases. Sixteen patients received whole liver radiotherapy (WLRT) between January 1997 and June 2013. A total dose of 21 Gy was delivered in 7 fractions. The median survival time after WLRT was 9 weeks. In univariate analysis, performance status, serum albumin and total bilirubin level, liver volume and extrahepatic metastases were associated with survival. The mean liver volume was significantly different between subgroups with and without pain relief (3,097 and 4,739 mL, respectively; p = 0.002). A larger liver volume is a poor prognostic factor for survival and also a negative predictive factor for response to WLRT. If patients who are referred for WLRT have large liver volume, they should be informed of the poor prognosis and should be closely observed during and after WLRT.

  2. Prognostic and predictive value of liver volume on colorectal cancer patients with unresectable liver metastases

    International Nuclear Information System (INIS)

    To determine the prognostic and predictive value of liver volume in colorectal cancer patients with unresectable liver metastases. Sixteen patients received whole liver radiotherapy (WLRT) between January 1997 and June 2013. A total dose of 21 Gy was delivered in 7 fractions. The median survival time after WLRT was 9 weeks. In univariate analysis, performance status, serum albumin and total bilirubin level, liver volume and extrahepatic metastases were associated with survival. The mean liver volume was significantly different between subgroups with and without pain relief (3,097 and 4,739 mL, respectively; p = 0.002). A larger liver volume is a poor prognostic factor for survival and also a negative predictive factor for response to WLRT. If patients who are referred for WLRT have large liver volume, they should be informed of the poor prognosis and should be closely observed during and after WLRT.

  3. The presence of old pulmonary tuberculosis is an independent prognostic factor for squamous cell lung cancer survival

    OpenAIRE

    Zhou, Yiming; Cui, Zhenling; Zhou, Xiao; Chen, Chang; Jiang, Sen; Hu, Zhongyi; Jiang, Gening

    2013-01-01

    Background Pulmonary tuberculosis (TB) is associated with an increased risk of lung cancer. Our study investigated whether the coexistence of an old pulmonary TB lesion is an independent prognostic factor for lung cancer survival in Chinese non-small cell lung cancer patients. Methods We performed a retrospective review of 782 non-small cell lung cancer patients who underwent surgical resection as their primary treatment in 2006 and were followed for 5 years. The associations between lung can...

  4. Prognostic indices in stereotactic radiotherapy of brain metastases of non-small cell lung cancer

    International Nuclear Information System (INIS)

    Our purpose was to analyze the long-term clinical outcome and to identify prognostic factors after Linac-based stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT) on patients with brain metastases (BM) from non-small cell lung cancer (NSCLC). We performed a retrospective analysis of survival on 90 patients who underwent SRS or FSRT of intracranial NSCLC metastases between 04/2004 and 05/2014 that had not undergone prior surgery or whole brain radiotherapy (WBRT) for BM. Follow-up data was analyzed until May 2015. Potential prognostic factors were examined in univariable and multivariable analyses. The Golden Grading System (GGS), the disease-specific graded prognostic assessment (DS-GPA), the RADES II prognostic index as well as the NSCLC-specific index proposed by Rades et al. in 2013 (NSCLC-RADES) were calculated and their predictive values were tested in univariable analysis. The median follow-up time of the surviving patients was 14 months. The overall survival (OS) rate was 51 % after 6 months and 29.9 % after 12 months. Statistically significant factors of better OS after univariable analysis were lower International Union Against Cancer (UICC) stage at first diagnosis, histology of adenocarcinoma, prior surgery of the primary tumor and lower total BM volume. After multivariable analysis adenocarcinoma histology remained a significant factor; higher Karnofsky Performance Score (KPS) and the presence of extracranial metastases (ECM) were also significant. The RADES II and the NSCLC-RADES indices were significant predictors of OS. However, the NSCLC-RADES failed to differentiate between intermediate- and low-risk patients. The DS-GPA and GGS were not statistically significant predictors of survival in univariable analysis. The ideal prognostic index has not been defined yet. We believe that more specific indices will be developed in the future. Our results indicate that the histologic subtype of NSCLC could add to the prognostic

  5. The prognostic value of molecular marker analysis in patients treated with trimodality therapy for esophageal cancer.

    Science.gov (United States)

    Harpole, D H; Moore, M B; Herndon, J E; Aloia, T; D'Amico, T A; Sporn, T; Parr, A; Linoila, I; Allegra, C

    2001-03-01

    The purpose of this study was to define the prognostic value of a group of molecular tumor markers in a well-staged population of patients treated with trimodality therapy for esophageal cancer. The original pretreatment paraffin-embedded endoscopic esophageal tumor biopsy material was obtained from 118 patients treated with concurrent cisplatin + 5-fluorouracil (5-FU) + 45 Gy radiation followed by resection from 1986 until 1997 at the Duke University Comprehensive Cancer Center. Three markers of possible platinum chemotherapy association [metallothionein (MT), glutathione S-transferase-pi (GST-pi), P-glycoprotein (P-gp or multidrug resistance)] and one marker of possible 5-FU association [thymidylate synthase (TS)] were measured using immunohistochemistry. The median cancer-free survival was 25.0 months, with a significantly improved survival for the 38 patients who had a complete response (P GST-pi, P-gp, and TS were associated with a decreased survival. MT was not significant in this population. Multivariate analysis identified high-level expression in two of the platinum markers (GST-pi and P-gp) and the 5-FU marker TS as independent predictors of early recurrence and death. In conclusion, this investigation measured three possible markers associated with platinum and one possible marker associated with 5-FU in a cohort of esophageal cancer patients. Independent prognostic significance was observed, which suggests that it may be possible to predict which patients may benefit most from trimodality therapy. These data need to be reproduced in a prospective investigation. PMID:11297249

  6. Prognostic value of stem cell quantification in stage II colon cancer.

    Directory of Open Access Journals (Sweden)

    Maria Angeles Vaz

    Full Text Available BACKGROUND: Cancer stem cells (CSCs are a subset of tumor cells with capacity to self-renew and generate the diverse cells that make up the tumor. The aim of this study is to evaluate the prognostic value of CSCs in a highly homogeneous population of stage II colon cancer. METHODS: One hundred stage II colon cancer patients treated by the same surgical team between 1977 and 2005 were retrospectively analyzed. None of the patients received adjuvant chemotherapy. Inmunohistochemistry expression of CD133, NANOG and CK20 was scored, using four levels: 50% positivity. Kaplan-Meier analysis and log rank test were used to compare survival. RESULTS: The average patient age was 68 years (patients were between 45-92 years of age and median follow up was 5.8 years. There was recurrent disease in 17 (17%; CD133 expression (defined by >10% positivity was shown in 60% of the tumors, in 95% for NANOG and 78% for CK20. No correlation was found among expression levels of CD133, NANOG or CK20 and relapse-free survival (RFS or overall survival (OS. However, a statistical significant correlation was found between established pathological prognostic factors and RFS and OS. CONCLUSIONS: Stem Cell quantification defined by CD133 and NANOG expression has no correlation with RFS or OS in this cohort of Stage II colon cancer.

  7. Tumor radiosensitivity (SF2) is a prognostic factor for local control in head and neck cancers

    International Nuclear Information System (INIS)

    Purpose: To evaluate prospectively the prognostic value of SF2 for local control and survival in patients undergoing radiation therapy for head and neck cancers. Methods and materials: Following informed consent tumor specimens were obtained from 156 patients with primary carcinomas of the head and neck region. The specimens were assessed for the ability to grow in vitro (colony forming efficiency, CFE) and inherent radiosensitivity measured as the surviving fraction at 2 Gy (SF2) using a soft-agar clonogenic assay. Patients were treated mainly with neoadjuvant chemotherapy plus radiation therapy usually as a combination of accelerated external beam and interstitial radiotherapy. The probabilities of local control and survival were analyzed by univariate, bivariate and Cox multivariate analyses. Results: Successful growth was achieved in 110/156 specimens and SF2 values were obtained from 99/156. Eighty four out of these patients underwent radical treatment. The median SF2 value for the 84 tumors was 0.40. At a mean follow-up time of 25 months (range 7-65) the median SF2 value of tumors from 14 patients who developed local recurrence was 0.53, which was significantly higher than the median of 0.38 for tumors from 70 patients without local recurrence (p = 0.015). Tumor SF2 was a significant prognostic factor for local control (p = 0.036), but not for overall survival (p 0.20). Tumor SF2 was an independent prognostic factor for local control within bivariate and Cox multivariate analyses. Conclusions: This study has shown that tumor radiosensitivity measured as SF2 is a significant prognostic factor for local control in head and neck cancers

  8. A retrospective analysis of survival and prognostic factors of male breast cancer from a single center

    International Nuclear Information System (INIS)

    Less than 1% of all breast cancer cases are found in men, who reportedly have inferior outcomes compared with matched women patients. Ethnic differences may also affect their prognosis. Here, we investigated overall survival (OS) and major prognostic factors for male breast cancer (MBC) in a cohort of Egyptian patients. We retrospectively analyzed OS in a cohort of 69 male patients with MBC who were surgically treated at the Mansoura Cancer Center, Egypt between 2000 and 2007. We registered demographic data, age, height, weight and body mass index, tumor size, histology, number of infiltrated axillary lymph nodes, hormone receptor (HR) status and metastatic presence, and TNM staging. Patients’ OS was the primary endpoint. Patients received treatment to the medical standards at the time of their diagnosis. In the 69 patients who met the inclusion criteria and had complete stored patient data, tumors ranged from T1c to T3. We could gather cancer-related survival data from only 56 patients. The collective 5-year survival in this cohort was 46.4%. Only five patients had distant metastasis at diagnosis, but they showed a null percent 5-year survival, whereas those with no lymph node infiltration showed a 100% 5-year survival. Lymph node status and tumor grading were the only prognostic factors that significantly affected OS. Lymph node status and tumor grade are the most important prognostic factors for overall survival of MBC in Egyptian male patients; whereas even remarkably low HR expression in MBC did not significantly affect OS. Further research is needed to understand the factors that affect this disease

  9. Lymph node ratio as a prognostic factor in head and neck cancer patients

    International Nuclear Information System (INIS)

    Lymph node status is one prognostic factor in head and neck cancer. The purpose of this study is to investigate the prognostic value of lymph node ratio (LNR) in head and neck cancer patients who received surgery plus postoperative chemoradiotherapy. From May 1991 to December 2012, a total of 117 head and neck cancer patients who received surgery plus postoperative chemoradiotherapy were analyzed. The primary sites were oral cavity (93), oropharynx (13), hypopharynx (6), and larynx (5). All patients had pathologically confirmed squamous cell carcinoma and 63 patients had neck lymph nodes metastasis. LNR was calculated for each patient. The endpoints were overall survival (OS), local failure-free survival (LFFS), and distant metastasis-free survival (DMFS). The median follow up time was 36 months, with a range from 3.4 to 222 months. The 3-year rates of OS, LFFS, and DMFS were 59.7, 70.3, and 81.8 %, respectively. The median value of LNR for lymph nodes positive patients was 0.1. In univariate analysis, patients with an LNR value less than 0.1 had better 3-year OS (67.0 % vs.41.0 %, p = 0.004), 3-year LFFS (76.1 % vs. 54.9 %, p = 0.015) and 3-year DMFS (87.2 % vs. 66.4 %, p = 0.06). Multivariate analysis revealed that LNR was an independent prognostic factor for OS (hazard ratio [HR] = 2.92; 95 % confidence interval [CI] = 1.367–6.242; p = 0.006) and LFFS (HR = 4.12; 95 % CI = 1.604–10.59; p = 0.003). LNR is an important prognosis factor for OS and LFFS in head and neck cancer patients. The online version of this article (doi:10.1186/s13014-015-0490-9) contains supplementary material, which is available to authorized users

  10. A profile of prognostic and molecular factors in European and Māori breast cancer patients

    International Nuclear Information System (INIS)

    New Zealand Māori have a poorer outcome from breast cancer than non-Māori, yet prognostic data are sparse. The objective of this study was to quantify levels of prognostic factors in a cohort of self-declared Māori and European breast cancer patients from Christchurch, New Zealand. Clinicopathological and survival data from 337 consecutive breast cancer patients (27 Māori, 310 European) were evaluated. Fewer tumours were high grade in Māori women than European women (p = 0.027). No significant ethnic differences were detected for node status, tumour type, tumour size, human epidermal growth factor receptor, oestrogen and progesterone receptor (ER/PR) status, or survival. In addition, tumour and serum samples from a sub-cohort of 14 Māori matched to 14 NZ European patients were analyzed by immunohistochemistry and enzyme linked immunosorbent assay for molecular prognostic factors. Significant correlations were detected between increased grade and increased levels of hypoxia inducible factor-1 (HIF-1α), glucose transporter-1 (GLUT-1), microvessel density (MVD) and cytokeratins CK5/6 (p < 0.05). High nodal status correlated with reduced carbonic anhydrase IX (CA-IX). Negative ER/PR status correlated with increased GLUT-1, CA-IX and MVD. Within the molecular factors, increased HIF-1α correlated with raised GLUT-1, MVD and CK5/6, and CK5/6 with GLUT-1 and MVD (p < 0.05). The small number of patients in this sub-cohort limited discrimination of ethnic differences. In this Christchurch cohort of breast cancer patients, Māori women were no more likely than European women to have pathological or molecular factors predictive of poor prognosis. These data contrast with data from the North Island NZ, and suggest potential regional differences

  11. Rational bases for the use of the Immunoscore in routine clinical settings as a prognostic and predictive biomarker in cancer patients.

    Science.gov (United States)

    Kirilovsky, Amos; Marliot, Florence; El Sissy, Carine; Haicheur, Nacilla; Galon, Jérôme; Pagès, Franck

    2016-08-01

    The American Joint Committee on Cancer/Union Internationale Contre le Cancer (AJCC/UICC) tumor, nodes, metastasis (TNM) classification system based on tumor features is used for prognosis estimation and treatment recommendations in most cancers. However, the clinical outcome can vary significantly among patients within the same tumor stage and TNM classification does not predict response to therapy. Therefore, many efforts have been focused on the identification of new markers. Multiple tumor cell-based approaches have been proposed but very few have been translated into the clinic. The recent demonstration of the essential role of the immune system in tumor progression has allowed great advances in the understanding of this complex disease and in the design of novel therapies. The analysis of the immune infiltrate by imaging techniques in large patient cohorts highlighted the prognostic impact of the in situ immune cell infiltrate in tumors. Moreover, the characterization of the immune infiltrates (e.g. type, density, distribution within the tumor, phenotype, activation status) in patients treated with checkpoint-blockade strategies could provide information to predict the disease outcome. In colorectal cancer, we have developed a prognostic score ('Immunoscore') that takes into account the distribution of the density of both CD3(+) lymphocytes and CD8(+) cytotoxic T cells in the tumor core and the invasive margin that could outperform TNM staging. Currently, an international retrospective study is under way to validate the Immunoscore prognostic performance in patients with colon cancer. The use of Immunoscore in clinical practice could improve the patients' prognostic assessment and therapeutic management. PMID:27121213

  12. Expression of Bmi-1 is a prognostic marker in bladder cancer

    Directory of Open Access Journals (Sweden)

    Xu Li-Hua

    2009-02-01

    Full Text Available Abstract Background The molecular mechanisms of the development and progression of bladder cancer are poorly understood. The objective of this study was to analyze the expression of Bmi-1 protein and its clinical significance in human bladder cancer. Methods We examined the expression of Bmi-1 mRNA and Bmi-1 protein by RT-PCR and Western blot, respectively in 14 paired bladder cancers and the adjacent normal tissues. The expression of Bmi-1 protein in 137 specimens of bladder cancer and 30 specimens of adjacent normal bladder tissue was determined by immunohistochemistry. Statistical analyses were applied to test the relationship between expression of Bmi-1, and clinicopathologic features and prognosis. Results Expression of Bmi-1 mRNA and protein was higher in bladder cancers than in the adjacent normal tissues in 14 paired samples (P P P P P > 0.5. In superficial bladder cancers, the expression of Bmi-1 protein in recurrent cases was higher than in recurrence-free cases (62.5% versus 13.7%, P P P > 0.05. Five-year survival in the group with higher Bmi-1 expression was 50.8%, while it was 78.5% in the group with lower Bmi-1 expression (P P Conclusion Expression of Bmi-1 was greater in bladder cancers than in the adjacent normal tissues. The examination of Bmi-1 protein expression is potentially valuable in prognostic evaluation of bladder cancer.

  13. Analyzing proteasomal subunit expression reveals Rpt4 as a prognostic marker in stage II colorectal cancer.

    LENUS (Irish Health Repository)

    2012-02-01

    Colorectal cancer is a leading cause of cancer-related deaths worldwide. Early diagnosis and treatment of colorectal cancer is the key to improving survival rates and as such a need exists to identify patients who may benefit from adjuvant chemotherapy. The dysregulation of the ubiquitin-proteasome system (UPS) has been implicated in oncogenesis and cancer cell survival, and proteasome inhibitors are in clinical use for a number of malignancies including multiple myeloma. In our study, we examined the protein expression of several key components of the UPS in colorectal cancer using immunohistochemistry to determine expression levels of ubiquitinylated proteins and the proteasomal subunits, 20S core and Rpt4 in a cohort of 228 patients with colon cancer. Multivariate Cox analysis revealed that neither the intensity of either ubiquitinylated proteins or the 20S core was predictive in either Stage II or III colon cancer for disease free survival or overall survival. In contrast, in Stage II patients increased Rpt4 staining was significantly associated with disease free survival (Cox proportional hazard ratio 0.605; p = 0.0217). Our data suggest that Rpt4 is an independent prognostic variable for Stage II colorectal cancer and may aid in the decision of which patients undergo adjuvant chemotherapy.

  14. Comparative survival analysis of breast cancer microarray studies identifies important prognostic genetic pathways

    Directory of Open Access Journals (Sweden)

    Liu Song

    2010-10-01

    Full Text Available Abstract Background An estimated 12% of females in the United States will develop breast cancer in their lifetime. Although, there are advances in treatment options including surgery and chemotherapy, breast cancer is still the second most lethal cancer in women. Thus, there is a clear need for better methods to predict prognosis for each breast cancer patient. With the advent of large genetic databases and the reduction in cost for the experiments, researchers are faced with choosing from a large pool of potential prognostic markers from numerous breast cancer gene expression profile studies. Methods Five microarray datasets related to breast cancer were examined using gene set analysis and the cancers were categorized into different subtypes using a scoring system based on genetic pathway activity. Results We have observed that significant genes in the individual studies show little reproducibility across the datasets. From our comparative analysis, using gene pathways with clinical variables is more reliable across studies and shows promise in assessing a patient's prognosis. Conclusions This study concludes that, in light of clinical variables, there are significant gene pathways in common across the datasets. Specifically, several pathways can further significantly stratify patients for survival. These candidate pathways should help to develop a panel of significant biomarkers for the prognosis of breast cancer patients in a clinical setting.

  15. SNPs in genes implicated in radiation response are associated with radiotoxicity and evoke roles as predictive and prognostic biomarkers

    International Nuclear Information System (INIS)

    Biomarkers are needed to individualize cancer radiation treatment. Therefore, we have investigated the association between various risk factors, including single nucleotide polymorphisms (SNPs) in candidate genes and late complications to radiotherapy in our nasopharyngeal cancer patients. A cohort of 155 patients was included. Normal tissue fibrosis was scored using RTOG/EORTC grading system. A total of 45 SNPs in 11 candidate genes (ATM, XRCC1, XRCC3, XRCC4, XRCC5, PRKDC, LIG4, TP53, HDM2, CDKN1A, TGFB1) were genotyped by direct genomic DNA sequencing. Patients with severe fibrosis (cases, G3-4, n = 48) were compared to controls (G0-2, n = 107). Univariate analysis showed significant association (P < 0.05) with radiation complications for 6 SNPs (ATM G/A rs1801516, HDM2 promoter T/G rs2279744 and T/A rs1196333, XRCC1 G/A rs25487, XRCC5 T/C rs1051677 and TGFB1 C/T rs1800469). In addition, Kaplan-Meier analyses have also highlighted significant association between genotypes and length of patients’ follow-up after radiotherapy. Multivariate logistic regression has further sustained these results suggesting predictive and prognostic roles of SNPs. Univariate and multivariate analysis suggest that radiation toxicity in radiotherapy patients are associated with certain SNPs, in genes including HDM2 promoter studied for the 1st time. These results support the use of SNPs as genetic predictive markers for clinical radiosensitivity and evoke a prognostic role for length of patients’ follow-up after radiotherapy

  16. Genetic and Prognostic Differences of Non-small Cell Lung Cancer between Elderly Patients and Younger Counterparts.

    Science.gov (United States)

    Suda, Kenichi; Tomizawa, Kenji; Mizuuchi, Hiroshi; Ito, Simon; Kitahara, Hirokazu; Shimamatsu, Shinichiro; Kohno, Mikihiro; Yoshida, Tsukihisa; Okamoto, Tatsuro; Maehara, Yoshihiko; Yatabe, Yasushi; Mitsudomi, Tetsuya

    2012-12-01

    Many elderly patients suffer from lung cancers, but it is not clear if their lung cancers differ from those of younger patients. In this study, we compared genetic and prognostic characteristics of lung cancers of patients aged ≥75 years with those of patients aged ≤ 64 years. In the genetic analysis, we explored 292 surgically treated non-squamous cell lung cancers with known mutational status of epidermal growth factor (EGFR) and anaplastic lymphoma kinase (ALK). In the prognostic analysis, we retrospectively analyzed 405 surgically treated non-small cell lung cancers (NSCLCs) before the era of routine clinical application of post-surgical adjuvant chemotherapy. Postsurgical recurrence-free survival (RFS) was compared between elderly patients and younger counterparts. The genetic analysis showed elderly non-squamous cell lung cancer patients to have higher prevalence of EGFR mutations (53.1 % vs 42.0%, P = 0.15) and lower prevalence of the ALK translocation (0 % vs 4.5%, P = 0.23) than their younger counterparts. The prognostic analysis showed postsurgical RFS was similar between the elderly NSCLC patients and the younger patients. However in multivariate analysis, adjusting for gender, smoking status, pathological stage, and histology, elderly patients had significantly worse prognoses (HR 1.57, 95% CI, 1.08-2.29; P = 0.02) compared with younger patients. These results suggest differences in genetic and prognostic aspects between elderly lung cancer patients and younger lung cancer patients. PMID:23251849

  17. The prognostic role of lymphovascular invasion in urothelial carcinoma of the bladder.

    Science.gov (United States)

    Mathieu, Romain; Lucca, Ilaria; Rouprêt, Morgan; Briganti, Alberto; Shariat, Shahrokh F

    2016-08-01

    Outcome prediction in patients with bladder cancer has improved through the development of nomograms and predictive models. However, integration of further characteristics such as lymphovascular invasion (LVI) might increase the accuracy and clinical utility of these instruments. Assessment and reporting of LVI in specimens from transurethral resection of the bladder tumour (TURBT) or biopsy in patients with non-muscle-invasive bladder cancer (NMIBC) or muscle-invasive bladder cancer (MIBC) might enable improved staging, prognostication and clinical decision-making. In NMIBC, presence of LVI in TURBT and biopsy samples seems to be associated with understaging and increased risks of disease recurrence and progression. In MIBC, presence of LVI is associated with features of aggressive disease and predicts recurrence and survival. Integration of LVI status into predictive models might aid clinical decision-making regarding intravesical instillation schedules and regimens, early radical cystectomy in patients with high-grade T1 disease and perioperative chemotherapy. However, LVI assessment is hampered by insufficient reproducibility and reliability, lack of routine evaluation and limited concordance between findings in TURBT and radical cystectomy specimens. Standardization of the pathological criteria defining LVI is warranted to improve its reporting in routine clinical practice and its utility as a care-changing prognostic marker. PMID:27431340

  18. Meta-analysis of several gene lists for distinct types of cancer: A simple way to reveal common prognostic markers

    OpenAIRE

    Sun Xiao; Yang Xinan

    2007-01-01

    Abstract Background Although prognostic biomarkers specific for particular cancers have been discovered, microarray analysis of gene expression profiles, supported by integrative analysis algorithms, helps to identify common factors in molecular oncology. Similarities of Ordered Gene Lists (SOGL) is a recently proposed approach to meta-analysis suitable for identifying features shared by two data sets. Here we extend the idea of SOGL to the detection of significant prognostic marker genes fro...

  19. The prognostic value of temporal in vitro and in vivo derived hypoxia gene-expression signatures in breast cancer

    International Nuclear Information System (INIS)

    Background and purpose: Recent data suggest that in vitro and in vivo derived hypoxia gene-expression signatures have prognostic power in breast and possibly other cancers. However, both tumour hypoxia and the biological adaptation to this stress are highly dynamic. Assessment of time-dependent gene-expression changes in response to hypoxia may thus provide additional biological insights and assist in predicting the impact of hypoxia on patient prognosis. Materials and methods: Transcriptome profiling was performed for three cell lines derived from diverse tumour-types after hypoxic exposure at eight time-points, which include a normoxic time-point. Time-dependent sets of co-regulated genes were identified from these data. Subsequently, gene ontology (GO) and pathway analyses were performed. The prognostic power of these novel signatures was assessed in parallel with previous in vitro and in vivo derived hypoxia signatures in a large breast cancer microarray meta-dataset (n = 2312). Results: We identified seven recurrent temporal and two general hypoxia signatures. GO and pathway analyses revealed regulation of both common and unique underlying biological processes within these signatures. None of the new or previously published in vitro signatures consisting of hypoxia-induced genes were prognostic in the large breast cancer dataset. In contrast, signatures of repressed genes, as well as the in vivo derived signatures of hypoxia-induced genes showed clear prognostic power. Conclusions: Only a subset of hypoxia-induced genes in vitro demonstrates prognostic value when evaluated in a large clinical dataset. Despite clear evidence of temporal patterns of gene-expression in vitro, the subset of prognostic hypoxia regulated genes cannot be identified based on temporal pattern alone. In vivo derived signatures appear to identify the prognostic hypoxia induced genes. The prognostic value of hypoxia-repressed genes is likely a surrogate for the known importance of

  20. Prognostic Aspects of DCE-MRI in Recurrent Rectal Cancer

    International Nuclear Information System (INIS)

    To explore whether pre-reoperative dynamic contrast-enhanced (DCE)-MRI findings correlate with clinical outcome in patients who undergo surgical treatment for recurrent rectal carcinoma. A retrospective study of DCE-MRI in patients with recurrent rectal cancer was performed after obtaining an IRB waiver. We queried our PACS from 1998 to 2012 for examinations performed for recurrent disease. Two radiologists in consensus outlined tumour regions of interest on perfusion images. We explored the correlation between Ktrans, Kep, Ve, AUC90 and AUC180 with time to re-recurrence of tumour, overall survival and resection margin status. Univariate Cox PH models were used for survival, while univariate logistic regression was used for margin status. Among 58 patients with pre-treatment DCE-MRI who underwent resection, 36 went directly to surgery and 18 had positive margins. Ktrans (0.55, P = 0.012) and Kep (0.93, P = 0.04) were inversely correlated with positive margins. No significant correlations were noted between Ktrans, Kep, Ve, AUC90 and AUC180 and overall survival or time to re-recurrence of tumour. Ktrans and Kep were significantly associated with clear resection margins; however overall survival and time to re-recurrence were not predicted. Such information might be helpful for treatment individualisation and deserves further investigation. (orig.)

  1. Excision Repair Cross-complementation Group 1 is a Prognostic Biomarker in Patients with Colorectal Cancer Receiving Chemotherapy

    Institute of Scientific and Technical Information of China (English)

    Mu-Xing Li; Xin-Yu Bi; Hong Zhao; Zhen Huang; Yue Han; Dong-Bin Zhao; Jian-Jun Zhao

    2016-01-01

    Background:Conflicting results about the association between expression level of excision repair cross-complementation group 1 (ERCC1) and clinical outcome in patients with colorectal cancer (CRC) receiving chemotherapy have been reported.Thus,we searched the available articles and performed the meta-analysis to elucidate the prognostic role of ERCC1 expression in patients with CRC.Methods:A thorough literature search using PubMed (Medline),Embase,Cochrane Library,Web of Science databases,and Chinese Science Citation Database was conducted to obtain the relevant studies.Pooled hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate the results.Results:A total of 11 studies were finally enrolled in this meta-analysis.Compared with patients with lower ERCC1 expression,patients with higher ERCC1 expression tended to have unfavorable overall survival (OS) (HR =2.325,95% CI:1.720-3.143,P < 0.001),progression-free survival (PFS) (HR =1.917,95% CI:1.366-2.691,P < 0.001) and poor response to chemotherapy (OR =0.491,95% CI:0.243-0.990,P =0.047).Subgroup analyses by treatment setting,ethnicity,HR extraction,detection methods,survival analysis,and study design demonstrated that our results were robust.Conclusions:ERCC1 expression may be taken as an effective prognostic factor predicting the response to chemotherapy,OS,and PFS.Further studies with better study design and longer follow-up are warranted in order to gain a deeper understanding of ERCC 1's prognostic value.

  2. RELATIONSHIP BETWEEN THE EXPRESSIONS OF SURVIVIN AND THE PROGNOSTIC RELATED FACTORS IN BREAST CANCER

    Institute of Scientific and Technical Information of China (English)

    SHEN Jing-hua; WANG Xiao-juan; SU He-ba-te; ZHAO Xiao-xia; TAO Ge-si

    2005-01-01

    Objective: To study the relationship between the Survivin expression and the histological grade, status of ER,expression of PS2 and the prognosis of patients with primary invasive breast cancer. Method: By using LSAB and SP immunohistochemical method, the expression of Survivin, PS2 and ER in 95 cases of invasive breast cancer were detected.Results: the positive rate of Survivin was 70.5% (67/95) and the expression of Survivin was positively related to the histological grade and status of PS2 and ER. The survival time after operation of patients without expression of Survivin was longer than those with positive Survivin. Conclusion: These data suggest that Survivin expression may be considered as a new unfavorable prognostic factor of breast cancer.

  3. Microvessel density and heparanase over-expression in clear cell renal cell cancer: correlations and prognostic significances

    Directory of Open Access Journals (Sweden)

    Ren Juchao

    2011-12-01

    Full Text Available Abstract Background Tumor angiogenesis is important in the progression of malignancies, and heparanase plays an important role in sustaining the pathology of clear cell renal cell cancer (ccRCC. The study was carried out to investigate the correlations between microvessel density (MVD and heparanase expression containing prognostic significances in the patients with ccRCC. Methods Specimens from 128 patients with ccRCC were investigated by immunohistochemistry for MVD. RT-PCR and immunohistochemistry were used to detect heparanase expression. Correlations between MVD, heparanase expression, and various clinico-pathological factors were studied. The prognostic significances of MVD and heparanase expression were also analysed. Results We discovered a statistically significant prevalence of higher MVD in ccRCC compared with adjacent normal renal tissues. MVD was positively correlated with TNM stage and distant metastasis in ccRCC patients, and was also correlated with the expression level of heparanase. Heparanase is over-expressed and correlated with TNM stage, histologic grade, distant metastasis and lymphatic metastasis in ccRCC. High MVD and heparanase over-expression inversely correlate with the survival of ccRCC patients. Conclusions Heparanase contributes to angiogenesis of ccRCC and over-expression of heparanase is an independent predictors of prognosis for ccRCC. MVD is correlated with tumor development and metastasis in ccRCC.

  4. Vascular endothelial growth factor and microvessel density for detection and prognostic evaluation of invasive breast cancer

    Institute of Scientific and Technical Information of China (English)

    Lukui Yang; Long Li; Xiangyu Cui; Dalei Yang

    2015-01-01

    Objective The purpose of this study was to evaluate the distribution of vascular endothelial growth factor (VEGF) and CD105-microvessel density (MVD) in invasive breast carcinomas. We also aimed to analyze the relationship between VEGF and MVD expression with other standard prognostic parameters associated with invasive breast cancer, such as size, grade, stage of the cancer, metastases, and tumor recurrence. Methods Immunohistochemistry via the Ultra SensitiveTM S-P method was used to detect VEGF and MVD expression in 128 cases of invasive breast carcinoma. Specimens were evaluated for CD105 expres-sion. Positively stained microvessels were counted in dense vascular foci under 400× magnification. MVD in the peripheral area adjacent to the lesion and in the central area within the lesion in invasive breast carcinomas and benign leisions groups were also assessed. Fifty cases of benign breast disease tissue were selected as the control group. Results Results showed that 64.1% of invasive breast cancer samples were VEGF-positive, higher than in benign breast disease tissue (22.0%, P 0.05). MVD of the peripheral area adja-cent to the lesion was significantly higher than those central area within the lesion in both invasive breast cancer and benign breast disease groups (P 50 years) or the two tumor diameter groups (≤2 cm vs.>2 cm), P > 0.05. Conclusion Overexpression of VEGF and MVD may be important biological markers for invasion and lymph node and distant metastases of invasive breast cancer. Combined detection of the two tumor mark-ers could provide better prognostic monitoring for disease recurrence and metastasis, as wel as aid with clinical staging of breast tumors. Prediction of the risk for metastasis and recurrence, as wel as recurrence patterns based on VEGF and MVD post-surgery, could aid design of better fol ow-up regimens and appro-priate treatment strategies for breast cancer patients.

  5. Brain metastases in lung cancer. Impact of prognostic factors on patient survival

    International Nuclear Information System (INIS)

    Background. Brain metastases are common patterns of dissemination in lung cancer patients. In this paper we would like to assess the pattern of brain metastases in lung cancer patients and the impact of prognostic factors on the survival of lung cancer patients with brain metastases. Patients and methods. In the year 1998 there were 974 registered patients with lung cancer in Slovenia, six hundred and fifteen of them were treated at the Institute of Oncology Ljubljana and we analyzed them. Among 615 patients 137 (22.3 %) of them have had brain metastases during a natural course of disease. Results. For 12 patients presenting with solitary brain metastases (most of them were undertaken metastasectomy) median survival was 7.6 months, while in patients with multiple brain metastases the median survival was 2.8 months (p 0.0018). Of the 137 patients 45 (32.8 %) were small cell lung cancer patients, 43 (31.4 %) were adenocarcinoma patients and 19 (13.9 %) were squamous cell carcinoma patients. Patients with performance status (WHO scale) less than 2 had the median survival time 3.7 months while patients with performance status 2 or more had median survival time 2.7 moths (p=0.0448). Conclusions. Patients with solitary brain metastases had better survival comparing with those who had multiple metastases. It is surprisingly that the portion of brain metastases patients with adenocarcinoma is almost equal to those with small-call lung cancer therefore, the prophylactic cranial radiation becomes actual for both groups of patients. The performance status of patients with brain metastases remains very important prognostic factor. (author)

  6. Variation of the prognostic significance of HER-2 expression in breast cancer according to tumor size.

    Science.gov (United States)

    Swede, Helen; Moysich, Kirsten B; Winston, Janet S; Hurd, Thelma C; Edge, Stephen B; Romero-Gutierrez, Maritza; Brooks, John S J; Michalek, Arthur M

    2003-01-01

    The prognostic importance of HER-2 status in breast cancer has been investigated extensively, but findings have not been uniform across immunohistochemical studies using fixed, paraffin-embedded specimens. We speculate that studies with an overrepresentation of large tumors might not produce evidence for an independent effect of a single marker because breast tumors of larger size tend to exhibit multiple adverse attributes as the malignancy advances through the metastatic cascade. Further, it has been posited that results from certain studies of biologic markers might be generalizable only to larger tumors because tumor repositories tend to house a disproportionate number of larger tumors. To test our hypothesis that the prognostic effect of HER-2 status might be modified by the size of the tumor, we conducted a survival analysis of a nested case-case sample of 156 women diagnosed with primary breast cancer from 1983 to 1995. Relative risks (RRs) and confidence intervals (CIs) for recurrence in relation to HER-2 status were estimated using a multivariate Cox proportional hazards model. Immunohistochemistry of archival tissue was used to detect HER-2 expression. Positive HER-2 status was associated with recurrence (RR = 4.24, 95% CI 1.30-13.78) among patients with axillary lymph node-positive involvement. This analysis identified an interaction (p < 0.01) between tumor size and overexpression. Stratification by tumor size revealed an increased risk of recurrence associated with HER-2-positive tumors that were prognostic studies using fixed tissue and might apply to other putative markers of prognosis in breast cancer. PMID:12603382

  7. Cancer patients' preferences for written prognostic information provided outside the clinical context.

    Science.gov (United States)

    Davey, H M; Butow, P N; Armstrong, B K

    2003-10-20

    Cancer patients' preferences for written prognostic information independent of the clinical context have not previously been investigated. This study aimed to assist a state cancer organisation to provide information to patients by assessing patients' understanding of statistical information; eliciting their preferences for framing, content and presentation; and assessing the acceptability of a card sort for obtaining preferences. With the exception of conditional and relative survival, initial difficulties in understanding statistical concepts were improved with a plain language explanation. Analysis of the interview transcripts revealed that participants generally supported the provision of written information about survival in booklets and on the Internet. They wanted positive, relevant and clear information. Participants said that the use of, and preferences for, this information would be affected by a patient's age, time since diagnosis, ability to cope with having cancer and the perceived credibility of the information source. They found the card sort acceptable, saying it made the assessment of understanding and selection of preferences easy. This study has identified two fundamental, and sometimes conflicting, factors underlying patients' preferences: the communication of hope and the need to understand information it has also identified patient characteristics thought to influence preferences. These factors and characteristics need to be taken into account when developing written prognostic information for patients. PMID:14562016

  8. Prognostic implication of PTPRH hypomethylation in non-small cell lung cancer.

    Science.gov (United States)

    Sato, Takashi; Soejima, Kenzo; Arai, Eri; Hamamoto, Junko; Yasuda, Hiroyuki; Arai, Daisuke; Ishioka, Kota; Ohgino, Keiko; Naoki, Katsuhiko; Kohno, Takashi; Tsuta, Koji; Watanabe, Shun-Ichi; Kanai, Yae; Betsuyaku, Tomoko

    2015-09-01

    PTPRH is a receptor-type protein tyrosine phosphatase thought to be a potential regulator of tumorigenesis. The aim of the present study was to clarify the significance of PTPRH expression and its regulation by DNA methylation in non-small cell lung cancer (NSCLC), especially in lung adenocarcinoma (LADC). PTPRH mRNA expression was examined in 89 NSCLC and corresponding non-cancerous tissues. The correlation between DNA methylation and PTPRH gene expression was investigated in another cohort that consisted of 145 patients with LADC, a major NSCLC subtype. Gene regulation by DNA methylation was assessed using a DNA methylation inhibitor. PTPRH mRNA expression was significantly upregulated in NSCLC. PTPRH DNA methylation was reduced in LADC samples and inversely correlated with mRNA expression. 5-Aza-2'-deoxycytidine treatment of lung cancer cell lines with low PTPRH expression, restored mRNA PTPRH expression levels. Furthermore, low PTPRH methylation was associated with shorter recurrence-free survival (P=1.64x10(-4)) and overall survival (P=5.54x10(-5)). Multivariate analysis revealed that PTPRH DNA methylation was an independent prognostic factor (P=6.88x10(-3)). It was confirmed that PTPRH is overexpressed in NSCLC. Furthermore, we determined that PTPRH is epigenetically regulated by DNA hypomethylation, with prognostic implications for LADC. PMID:26134684

  9. Learning curve: the surgeon as a prognostic factor in colorectal cancer surgery.

    Science.gov (United States)

    Renzulli, Pietro; Laffer, Urban T

    2005-01-01

    The individual surgeon is an independent prognostic factor for outcome in colorectal cancer surgery. The surgeon's learning curve is therefore directly related to the patient's outcome. The exact shape of the learning curve, however, is unknown. The present study reviewed supervision, training/teaching, specialization, surgeon's caseload, and hospital's caseload as the five main surgeon- and hospital-related confounding factors for outcome, and examined their influence on the learning curve as well as their interactions and prognostic significance. All five confounding factors were related to outcome. The highest degree of evidence, however, was found for training/teaching (introduction of total mesorectal excision), specialization in colorectal surgery (special interest, board-certification, specialized colorectal cancer units), and the surgeon's caseload. Five surgeon- and hospital-related factors directly influence the surgeon's learning curve and are therefore rightly considered predictors of outcome in colorectal cancer surgery. Improvements in supervision, training/teaching, specialization, the surgeon's caseload, and the hospital's caseload will therefore translate into enhanced patient outcome. PMID:15865024

  10. [Diagnostic problems and prognostic factors in prostate cancer].

    Science.gov (United States)

    Tarján, Miklós

    2016-03-01

    We aimed to refine the methodology for discriminating ductal (DAP) and acinar adenocarcinomas (AAP) of the prostate preoperatively with a high degree of accuracy, and confirm that prostate carcinoma of ductal origin is a more aggressive subtype. Moreover, we intended to evaluate the clinical utility of transrectal ultrasound-guided systematic sextant or octant biopsies in prediction of extracapsular extension (ECE) at radical prostatectomy. A blinded retrospective analysis of 3-dimensional histology specimens from 110 consecutive radical prostatectomy (RP) cases operated between 2000 and 2006 was carried out (average follow-up: 5.1 years). The samples were also analyzed for 9 different biomarkers. We performed a retrospective analysis of 84 cases of patients who underwent transrectal ultrasound-guided systematic sextant (in 60 cases) or octant (in 24 cases) biopsy. The presence of ECE was correlated to the number of positive biopsies on each side of the prostate by chi-square analysis. Sensitivity, specificity, positive and negative predictive values were calculated for both positive (two or three positive biopsies per side) and negative (no or only one positive biopsy per side) test results. The number of positive cores was thereafter combined with two other parameters: prostate-specific antigen (PSA) and Gleason score. 3-dimensional and conventional histology classified 97 cases of AAP and 13 cases of DAP. DAP cases had a significantly greater frequency of pT3a and more advanced cancers (p20 mm tumor focus (p=0.0020), highgrade PIN (p=0.0079), Gleason score ≥7 (p10 ng/ml vs. ≤10 ng/ml and more than one positive cores vs. 0 or 1 positives) identified patients at high or low risk of ECE, respectively. On the extremes, with only lowrisk parameters none of the 10 patients, while 77% of those with high-risk group had ECE at RP. Both 3-dimensional histology and the three selected biomarkers can accurately distinguish DAP from AAP. This discriminatory ability offers

  11. Prognostic impact of breast cancer subtypes in elderly patients.

    Science.gov (United States)

    Bergen, E S; Tichy, C; Berghoff, A S; Rudas, M; Dubsky, P; Bago-Horvath, Z; Mader, R M; Exner, R; Gnant, M; Zielinski, C C; Steger, G G; Preusser, M; Bartsch, R

    2016-05-01

    We aimed to analyse the impact of breast cancer (BC) subtypes on the clinical course of disease with special emphasis on the occurrence of brain metastases (BM) and outcome in an elderly BC population. A total number of 706 patients ≥65 years receiving treatment for BC from 2007 to 2011 were identified from a BC database. 62 patients diagnosed with DCIS and 73 patients with incomplete datasets were excluded, leaving 571 patients for this analysis. Patient characteristics, biological tumour subtypes, and clinical outcome including overall survival (OS) were obtained by retrospective chart review. 380/571 (66, 5 %) patients aged 65-74 years were grouped among the young-old, 182/571 (31.9 %) patients aged 75-84 years among the old-old, and 29/571 (5.1 %) patients aged ≥85 years among the oldest-old. 392/571 (68.8 %) patients presented with luminal BC, 119/571 (20.8 %) with HER2-positive, and 59/571 (10.3 %) with triple-negative BC (TNBC). At 38 months median follow-up, 115/571 (20.1 %) patients presented with distant recurrence. A higher recurrence rate was observed in the HER2-positive subtype (43/119 (36.1 %)), as compared to TNBC (15/59 (25.4 %)) and luminal BC (57/392 (14.5 %); p < 0.001). BM were detected at a significantly higher rate in HER2-positive BC patients (9/119 (7.6 %)), as compared to TNBC (2/59 (3.4 %)) and luminal BC patients (6/392 (1.5 %); p = 0.003). Diagnosis of metastatic disease (HR 7.7; 95 % CI 5.2-11.4; p < 0.001) as well as development of BM (HR 3.5; 95 % CI 1.9-6.4; p < 0.001) had a significantly negative impact on OS in a time-dependent covariate cox regression model. In contrast to younger BC patients, outcome in this large cohort of elderly patients suggests that HER2-positive disease-not TNBC-featured the most aggressive clinical course with the highest rates of metastatic spread and BM. In-depth analysis regarding a potentially distinct biology of TNBC in elderly is therefore warranted. PMID:27107570

  12. Salivary gland carcinomas: prognostic factors for local control and distant metastasis, the role of radiotherapy

    International Nuclear Information System (INIS)

    Purpose: The Dutch Head and Neck Oncology Cooperative Group, in which head and neck groups of all University hospitals and the two cancer institutes are represented, initiated a retrospective study concerning salivary gland carcinomas. A majority of Dutch patients with head and neck carcinomas are treated in the participating centres, and the follow-up is precise. Prognostic factors for local control and survival were studied, with special interest in the role of treatment and the role of histologic type. Methods and materials: Results were obtained of 568 patients with a mean follow-up time of 5 years. The parotid gland was involved in 59%, the submandibular gland in 14%, oral cavity in 24% and 3% was located elsewhere. Mean age was 59 years (range 8-100 yr), 48% was female. T-stage was T1 in 27%, T2 in 44%, T3 in 19% and T4 in 11%. Positive necknodes were seen in 15%, 3% was initially M1. Histologic type was acinic cell carcinoma in 12%, mucoepidermoid ca. in 16%, adenoid cystic ca. in 26%, adenoca. in 24%, carcinoma in pleomorphic adenoma in 8%, squamous cell ca. in 6% and undifferentiated ca. in 7%. Resection margins were radical in 37%, close in 20% and irradical in 40% (3% unknown). Surgery was the primary treatment in 501 patients, combined with postoperative radiotherapy (50-70 Gy, mean dose 62 Gy) in 389 patients. Radiotherapy was the primary treatment in 40 patients (18 M1, 30% N+), 20 patients were not treated and 7 patients were treated otherwise. For statistical analysis the Cox PH regression analysis was used (SPSS-PC+). Results: Actuarial local control after 8 years was 80% for surgery alone and 92% for the combined modality (in which more advanced cases prevaled). Independent factors for local control in the surgery±radiotherapy group were: I:T-stage (T3 vs T1-2: RR 3.7; T4 vs T1-2: RR 11.7), II: anatomic site (oral cavity vs parotid and submandibular gland: RR 0.2) and III: treatment modality (surgery alone vs surgery+radiotherapy: RR 7.0). Bone

  13. Clinical features and prognostic factors for patients with bone metastases from prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Jian He; Zhao-Chong Zeng; Ping Yang; Bing Chen; We Jiang; Shi-Suo Du

    2012-01-01

    To identify the clinical features and independent predictors of survival in patients with bone metastases from prostate cancer (PCa).We retrospectively analysed 115 PCa patients with bone metastases between 1997 and 2009.The overall survival rate after bone metastases was calculated using the Kaplan-Meier method.The prognostic factors were identified by univariate analysis using a log-rank test and by multivariate analysis using Cox proportional hazards regression models.The follow-up rate was 100%,the follow-up cases during 1,3 and 5 years were 103,79 and 55,respectively.The 1-,3- and 5-year survival rates were 89.1%,60.9% and 49.8%,respectively,with a median survival time of 48.5 months for patients with bone metastases from PCa.In univariate analysis,age,Gleason score,clinical stage,the number of bone lesions,alkaline phosphatase (ALP) level,invasion of neighbouring organs and non-regional lymph node metastases were correlated with prognosis.By multivariate analysis using Cox regression,ALP level,Gleason score and non-regional lymph node metastases were independent prognostic factors.These prognostic factors will help us to determine the appropriate dose and fraction of radiotherapy for these patients.

  14. Prognostic factors for the survival of 66 cases with extensive stage-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Heng Cao; Yonggui Hong; Shouran Zhao; Nengchao Wang; Fuyou Zhou; Xiaodong Xie

    2016-01-01

    Objective The objective of this retrospective study was to investigate the prognostic factors associated with survival among patients with extensive stage-smal cel lung cancer (ES-SCLC). Methods Clinical data from 66 patients with ES-SCLC diagnosed via histopathology or cytology between July 2005 and July 2009 at Anyang Tumor Hospital (China) were analyzed. Univariate and multivariate Kaplan-Meier, log-rank, and Cox proportional hazard regression analyses were conducted. Results The 12-, 24-, and 36-month survival rates among patients with ES-SCLC were 40.9%, 13.6%, and 6.1%, respectively. The median survival time (MST) was 10 months. Univariate analyses indicated that weight loss, eficacy of first-line chemotherapy, total number of chemotherapy cycles, treatment meth-od, and serum sodium levels significantly influenced survival among patients with ES-SCLC. Multivariate analyses suggested that the eficacy of first-line chemotherapy, total number of chemotherapy cycles, and serum sodium levels were independent prognostic factors associated with survival. Conclusion The eficacy of first-line chemotherapy, total number of chemotherapy cycles, and serum sodium levels are important prognostic factors for patients with ES-SCLC.

  15. Primary spinal epidural lymphoma: Patients' profile, outcome, and prognostic factors: A multicenter Rare Cancer Network study

    International Nuclear Information System (INIS)

    Purpose To assess the clinical profile, treatment outcome, and prognostic factors in primary spinal epidural lymphoma (PSEL). Methods and Materials Between 1982 and 2002, 52 consecutive patients with PSEL were treated in nine institutions of the Rare Cancer Network. Forty-eight patients had an Ann Arbor stage IE and four had a stage IIE. Forty-eight patients underwent decompressive laminectomy, all received radiotherapy (RT) with (n = 32) or without chemotherapy (n = 20). Median RT dose was 36 Gy (range, 6-50 Gy). Results Six (11%) patients progressed locally and 22 (42%) had a systemic relapse. At last follow-up, 28 patients were alive and 24 had died. The 5-year overall survival, disease-free survival, and local control were 69%, 57%, and 88%, respectively. In univariate analyses, favorable prognostic factors were younger age and complete neurologic response. Multivariate analysis showed that combined modality treatment, RT volume, total dose more than 36 Gy, tumor resection, and complete neurologic response were favorable prognostic factors. Conclusions Primary spinal epidural lymphoma has distinct clinical features and outcome, with a relatively good prognosis. After therapy, local control is excellent and systemic relapse occurs in less than half the cases. Combined modality treatment appears to be superior to RT alone

  16. Primary breast lymphoma: Patient profile, outcome and prognostic factors. A multicentre Rare Cancer Network study

    Directory of Open Access Journals (Sweden)

    Gutiérrez Cristina

    2008-04-01

    Full Text Available Abstract Background To asses the clinical profile, treatment outcome and prognostic factors in primary breast lymphoma (PBL. Methods Between 1970 and 2000, 84 consecutive patients with PBL were treated in 20 institutions of the Rare Cancer Network. Forty-six patients had Ann Arbor stage IE, 33 stage IIE, 1 stage IIIE, 2 stage IVE and 2 an unknown stage. Twenty-one underwent a mastectomy, 39 conservative surgery and 23 biopsy; 51 received radiotherapy (RT with (n = 37 or without (n = 14 chemotherapy. Median RT dose was 40 Gy (range 12–55 Gy. Results Ten (12% patients progressed locally and 43 (55% had a systemic relapse. Central nervous system (CNS was the site of relapse in 12 (14% cases. The 5-yr overall survival, lymphoma-specific survival, disease-free survival and local control rates were 53%, 59%, 41% and 87% respectively. In the univariate analyses, favorable prognostic factors were early stage, conservative surgery, RT administration and combined modality treatment. Multivariate analysis showed that early stage and the use of RT were favorable prognostic factors. Conclusion The outcome of PBL is fair. Local control is excellent with RT or combined modality treatment but systemic relapses, including that in the CNS, occurs frequently.

  17. The comparison of thrombocytosis and platelet-lymphocyte ratio as potential prognostic markers in colorectal cancer

    DEFF Research Database (Denmark)

    Baranyai, Zsolt; Krzystanek, Marcin; Josa, Valeria;

    2014-01-01

    . Clinicopathological data of 10 years were collected retrospectively from 336 patients with CRC and 118 patients with mCRC. Both in the CRC and the mCRC group overall survival (OS) was significantly worse in patients who had elevated platelet count (hazard ratio [HR] = 2.2, p ...The aim of the present study was to analyse the preoperative platelet count and the platelet-lymphocyte ratio (PLR) in patients with colorectal cancer (CRC) of different stages and with hepatic metastasis of CRC (mCRC) and to compare these factors as potential prognostic markers...

  18. Analysis of clinical prognostic factors in patients with cancer of oral cavity and throat after radiotherapy

    International Nuclear Information System (INIS)

    Statistically significant factors influencing the prognosis of the survival in the patients with locally disseminated cancer of the oral cavity and throat after radiotherapy are the degree of the regional nodes involvement, the stage of the disease, localization of the primary tumor, sex, conditional group and the degree of the tumor regression at the end of the treatment. Independent prognostic factors of better survival are stage 3 of the disease, female sex, A group (female patients, men with stage 3 (all localizations) and stage 4 (nasopharynx and upper jaw) diseases)

  19. Ectopic expression of B and T lymphocyte attenuator in gastric cancer: a potential independent prognostic factor in patients with gastric cancer.

    Science.gov (United States)

    Feng, Xing-Yu; Wen, Xi-Zhi; Tan, Xiao-Jing; Hou, Jing-Hui; Ding, Ya; Wang, Ke-Feng; Dong, Jun; Zhou, Zhi-Wei; Chen, Ying-Bo; Zhang, Xiao-Shi

    2015-01-01

    It has been confirmed that B and T lymphocyte attenuator (BTLA; also known as CD272) is a novel co--inhibitory molecule that exhibits a critical role in restraining cell-mediated antitumor immunity. The present study aimed to investigate the expression and prognostic significance of BTLA in gastric adenocarcinoma. Immunohistochemical (IHC) staining was performed to investigate BTLA expression in gastric cancer tissues and normal mucosal tissues. In total, 123 pathologically confirmed specimens were obtained from stage IIIa gastric cancers. A correlation test, Kaplan-Meier curves, and a Cox proportional hazards regression model were used to analyze the data. No BTLA staining in the normal tissues was found, while BTLA-stained gastric carcinoma cells were detected in 75.6% (93/123) of the gastric cancer specimens. High expression levels of BTLA were detected in 31.7% (39/123) of the specimens, while low expression levels were detected in 68.3% (84/123) of the specimens. High BTLA expression levels were associated with shorter survival time, as confirmed by univariate and multivariate analyses. These findings provide a basis for the concept that high BTLA expression levels in gastric cancer, identified by IHC, are an independent biomarker for the poor prognosis of patients with gastric cancer. PMID:25334051

  20. Tumor Volume Reduction Rate After Preoperative Chemoradiotherapy as a Prognostic Factor in Locally Advanced Rectal Cancer

    International Nuclear Information System (INIS)

    Purpose: To investigate the prognostic significance of tumor volume reduction rate (TVRR) after preoperative chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC). Methods and Materials: In total, 430 primary LARC (cT3–4) patients who were treated with preoperative CRT and curative radical surgery between May 2002 and March 2008 were analyzed retrospectively. Pre- and post-CRT tumor volumes were measured using three-dimensional region-of-interest MR volumetry. Tumor volume reduction rate was determined using the equation TVRR (%) = (pre-CRT tumor volume − post-CRT tumor volume) × 100/pre-CRT tumor volume. The median follow-up period was 64 months (range, 27–99 months) for survivors. Endpoints were disease-free survival (DFS) and overall survival (OS). Results: The median TVRR was 70.2% (mean, 64.7% ± 22.6%; range, 0–100%). Downstaging (ypT0–2N0M0) occurred in 183 patients (42.6%). The 5-year DFS and OS rates were 77.7% and 86.3%, respectively. In the analysis that included pre-CRT and post-CRT tumor volumes and TVRR as continuous variables, only TVRR was an independent prognostic factor. Tumor volume reduction rate was categorized according to a cutoff value of 45% and included with clinicopathologic factors in the multivariate analysis; ypN status, circumferential resection margin, and TVRR were significant prognostic factors for both DFS and OS. Conclusions: Tumor volume reduction rate was a significant prognostic factor in LARC patients receiving preoperative CRT. Tumor volume reduction rate data may be useful for tailoring surgery and postoperative adjuvant therapy after preoperative CRT.

  1. Plasma hyaluronic acid level as a prognostic and monitoring marker of metastatic breast cancer.

    Science.gov (United States)

    Peng, Cike; Wallwiener, Markus; Rudolph, Anja; Ćuk, Katarina; Eilber, Ursula; Celik, Muhabbet; Modugno, Caroline; Trumpp, Andreas; Heil, Jörg; Marmé, Frederik; Madhavan, Dharanija; Nees, Juliane; Riethdorf, Sabine; Schott, Sarah; Sohn, Christof; Pantel, Klaus; Schneeweiss, Andreas; Chang-Claude, Jenny; Yang, Rongxi; Burwinkel, Barbara

    2016-05-15

    Conventional tumor markers have limited value for prognostication and treatment monitoring in metastatic breast cancer (MBC) patients and novel circulating tumor markers therefore need to be explored. Hyaluronic acid (HA) is a major macropolysaccharide in the extracellular matrix and is reported to be associated with tumor progression. In our study, we investigated plasma HA level with respect to progression free survival (PFS) and overall survival (OS), as well as the treatment monitoring value in MBC patients. The prognostic value of plasma HA level was investigated in a discovery cohort of 212 MBC patients with 2.5-year follow-up and validated in an independent validation cohort of 334 patients with 5-year follow-up. The treatment monitoring value of plasma HA level was investigated in 61 MBC patients from discovery cohort who had been radiographically examined after first complete cycle of chemo therapy. We found a robust association between high plasma HA level and poor prognosis of MBC patients in both discovery (pPFS  = 7.92 × 10(-6) and pOS  = 5.27 × 10(-5) ) and validation studies (pPFS  = 3.66 × 10(-4) and pOS  = 1.43 × 10(-4) ). In the discovery cohort, the plasma HA level displayed independent prognostic value after adjusted for age and clinicopathological factors, with respect to PFS and OS. Further, the decrease of plasma HA level displayed good concordance with treatment response evaluated by radiographic examination (AUC = 0.79). Plasma HA level displays prognostic value, as well as treatment monitoring value for MBC patients. PMID:26686298

  2. Immunohistochemical detection of osteopontin in advanced head-and-neck cancer: Prognostic role and correlation with oxygen electrode measurements, hypoxia-inducible-factor-1α-related markers, and hemoglobin levels

    International Nuclear Information System (INIS)

    Purpose: The tumor-associated glycoprotein osteopontin (OPN) is discussed as a plasma marker of tumor hypoxia. However, the association of immunohistochemical OPN expression in tumor sections with tumor oxygenation parameters (HF5, median pO2), the hypoxia-related markers hypoxia-inducible factor-1α (HIF-1α) and carbonic anhydrase IX (CAIX), or hemoglobin and systemic vascular endothelial growth factor (VEGF) levels has not been investigated. Methods and Materials: Tumor tissue sections of 34 patients with advanced head-and-neck cancer treated with radiotherapy were assessed by immunochemistry for the expression of OPN, HIF-1α, and CA IX. Relationship of OPN expression with tumor oxygenation parameters (HF5, median pO2), HIF-1α and CA IX expression, hemoglobin and serum VEGF level, and clinical parameters was studied. Results: Bivariate analysis showed a significant correlation of positive OPN staining with low hemoglobin level (p = 0.02), high HIF-1α expression (p = 0.02), and high serum vascular endothelial growth factor level (p = 0.02) for advanced head-and-neck cancer. Furthermore, considering the 31 Stage IV patients, the median pO2 correlated significantly with the OPN expression (p = 0.02). OPN expression alone had only a small impact on prognosis. However, in a univariate Cox proportional hazard regression model, the expression of either OPN or HIF-1α or CA IX was associated with a 4.1-fold increased risk of death (p = 0.02) compared with negativity of all three markers. Conclusion: Osteopontin expression detected immunohistochemically is associated with oxygenation parameters in advanced head-and-neck cancer. When the results of OPN, HIF-1α, and CA IX immunohistochemistry are combined into a hypoxic profile, a strong and statistically significant impact on overall survival is found

  3. Discovery of a Novel Immune Gene Signature with Profound Prognostic Value in Colorectal Cancer: A Model of Cooperativity Disorientation Created in the Process from Development to Cancer.

    Directory of Open Access Journals (Sweden)

    Ning An

    Full Text Available Immune response-related genes play a major role in colorectal carcinogenesis by mediating inflammation or immune-surveillance evasion. Although remarkable progress has been made to investigate the underlying mechanism, the understanding of the complicated carcinogenesis process was enormously hindered by large-scale tumor heterogeneity. Development and carcinogenesis share striking similarities in their cellular behavior and underlying molecular mechanisms. The association between embryonic development and carcinogenesis makes embryonic development a viable reference model for studying cancer thereby circumventing the potentially misleading complexity of tumor heterogeneity. Here we proposed that the immune genes, responsible for intra-immune cooperativity disorientation (defined in this study as disruption of developmental expression correlation patterns during carcinogenesis, probably contain untapped prognostic resource of colorectal cancer. In this study, we determined the mRNA expression profile of 137 human biopsy samples, including samples from different stages of human colonic development, colorectal precancerous progression and colorectal cancer samples, among which 60 were also used to generate miRNA expression profile. We originally established Spearman correlation transition model to quantify the cooperativity disorientation associated with the transition from normal to precancerous to cancer tissue, in conjunction with miRNA-mRNA regulatory network and machine learning algorithm to identify genes with prognostic value. Finally, a 12-gene signature was extracted, whose prognostic value was evaluated using Kaplan-Meier survival analysis in five independent datasets. Using the log-rank test, the 12-gene signature was closely related to overall survival in four datasets (GSE17536, n = 177, p = 0.0054; GSE17537, n = 55, p = 0.0039; GSE39582, n = 562, p = 0.13; GSE39084, n = 70, p = 0.11, and significantly associated with disease

  4. Discovery of a Novel Immune Gene Signature with Profound Prognostic Value in Colorectal Cancer: A Model of Cooperativity Disorientation Created in the Process from Development to Cancer.

    Science.gov (United States)

    An, Ning; Shi, Xiaoyu; Zhang, Yueming; Lv, Ning; Feng, Lin; Di, Xuebing; Han, Naijun; Wang, Guiqi; Cheng, Shujun; Zhang, Kaitai

    2015-01-01

    Immune response-related genes play a major role in colorectal carcinogenesis by mediating inflammation or immune-surveillance evasion. Although remarkable progress has been made to investigate the underlying mechanism, the understanding of the complicated carcinogenesis process was enormously hindered by large-scale tumor heterogeneity. Development and carcinogenesis share striking similarities in their cellular behavior and underlying molecular mechanisms. The association between embryonic development and carcinogenesis makes embryonic development a viable reference model for studying cancer thereby circumventing the potentially misleading complexity of tumor heterogeneity. Here we proposed that the immune genes, responsible for intra-immune cooperativity disorientation (defined in this study as disruption of developmental expression correlation patterns during carcinogenesis), probably contain untapped prognostic resource of colorectal cancer. In this study, we determined the mRNA expression profile of 137 human biopsy samples, including samples from different stages of human colonic development, colorectal precancerous progression and colorectal cancer samples, among which 60 were also used to generate miRNA expression profile. We originally established Spearman correlation transition model to quantify the cooperativity disorientation associated with the transition from normal to precancerous to cancer tissue, in conjunction with miRNA-mRNA regulatory network and machine learning algorithm to identify genes with prognostic value. Finally, a 12-gene signature was extracted, whose prognostic value was evaluated using Kaplan-Meier survival analysis in five independent datasets. Using the log-rank test, the 12-gene signature was closely related to overall survival in four datasets (GSE17536, n = 177, p = 0.0054; GSE17537, n = 55, p = 0.0039; GSE39582, n = 562, p = 0.13; GSE39084, n = 70, p = 0.11), and significantly associated with disease-free survival in four

  5. Independent prognostic value of angiogenesis and the level of plasminogen activator inhibitor type 1 in breast cancer patients

    DEFF Research Database (Denmark)

    Hansen, S; Overgaard, J; Rose, C;

    2003-01-01

    Tumour angiogenesis and the levels of plasminogen activator inhibitor type 1 (PAI-1) are both informative prognostic markers in breast cancer. In cell cultures and in animal model systems, PAI-1 has a proangiogenic effect. To evaluate the interrelationship of angiogenesis and the PAI-1 level in b...... Chalkley count are independent prognostic markers for recurrence-free survival in patients with primary breast cancer, suggesting that the prognostic impact of PAI-1 is not only based on its involvement in angiogenesis....... breast cancer, we have evaluated the prognostic value of those factors in a total of 228 patients with primary, unilateral, invasive breast cancer, evaluated at a median follow-up time of 12 years. Microvessels were immunohistochemically stained by antibodies against CD34 and quantitated by the Chalkley...... overall survival. In the multivariate analysis, the uPA level did not show independent prognostic impact for any of the analysed end points. In contrast, the risk of recurrence was independently and significantly predicted by both the PAI-1 level and the Chalkley count, with a hazard ratio (95% CI) of 1...

  6. Elevated Pretreatment Serum Concentration of YKL-40-An Independent Prognostic Biomarker for Poor Survival in Patients With Metastatic Nonsmall Cell Lung Cancer

    DEFF Research Database (Denmark)

    Thom, I.; Andritzky, B.; Schuch, G.;

    2010-01-01

    BACKGROUND: The glycoprotein YKL-40 is synthesized both by cancer cells and by tumor-associated macrophages and plays a functional role in tumor progression. Consequently, high serum YKL-40 levels have been associated with a poor prognosis in patients with several cancer types. However, the role ...... was identified as a new, independent prognostic biomarker in patients with metastatic NSCLC and may help to determine the individual prognosis of these patients. Cancer 2010;116:4114-21. (C) 2010 American Cancer Society......BACKGROUND: The glycoprotein YKL-40 is synthesized both by cancer cells and by tumor-associated macrophages and plays a functional role in tumor progression. Consequently, high serum YKL-40 levels have been associated with a poor prognosis in patients with several cancer types. However, the role of...... YKL-40 has not been established in non-small cell lung cancer (NSCLC). METHODS: Pretreatment serum levels of YKL-40 were determined in 189 patients with NSCLC (143 men and 46 women; median age, 62 years;, age range, 41-76 years). Twelve percent of patients had stage IIIB disease, and 88% had stage IV...

  7. Intraoperative radiotherapy combined with resection for pancreatic cancer. Analysis of survival rates and prognostic factors

    International Nuclear Information System (INIS)

    The purpose of this study was to evaluate the efficiency of intraoperative radiotherapy (IORT) combined with surgical resection. Subjects were consecutive 69 patients with pancreatic cancer treated with surgery alone (n=31) or surgical resection combined with IORT (n=38) in a 13 year period between 1991 and 2003. We evaluated the effects of IORT against local recurrence of cancer and patients' survival, retrospectively. Furthermore, clinicopathological factors affecting the 5-year survival rate in the two groups were comparatively investigated. The IORT group showed a significantly lower local recurrence rate of cancer than that in the surgery alone group (7.8% and 22.6%, respectively; p<0.05). The 5-year survival probability in the IORT group was significantly higher than that in the surgery alone group (29.9% and 3.4%, respectively; p<0.05). According to the Japanese classification of pancreatic cancer, cancers located in the pancreas body or tail, no local residual cancer post operative procedure (R0), low grade local cancer progression (t1, 2), and low grade intrapancreatic neural invasion (ne0, 1) were significantly better prognostic factors in the IORT group than those in the surgery alone group. There were no significant differences between the both groups in the 5-year survival rate in terms of the sex of the patients, cancer of the pancreas head, histological type, more than R1, the presence of lymph node involvement, ne2-3, and clinical stages. IORT is a useful intraoperative adjuvant therapy for pancreatic cancer, when the curative resection is achieved. Our data have suggested that IORT suppresses the local recurrence of cancer and provides the significant survival benefit for those patients. (author)

  8. Endocan-expressing microvessel density as a prognostic factor for survival in human gastric cancer

    Science.gov (United States)

    Chang, Yuan; Niu, Wei; Lian, Pei-Long; Wang, Xian-Qiang; Meng, Zhi-Xin; Liu, Yi; Zhao, Rui

    2016-01-01

    AIM: To investigate the expression of endocan in tumour vessels and the relationships between endocan and the expression of vascular endothelial growth factor (VEGF) and prognosis in gastric cancer. METHODS: This study included 142 patients with confirmed gastric cancer in a single cancer centre between 2008 and 2009. Clinicopathologic features were determined, and an immunohistochemical analysis of endocan-expressing microvessel density (MVD) (endocan-MVD), VEGF and vascular endothelial growth factor receptor 2 (VEGFR2) was performed. Potential relationships between endocan-MVD and clinicopathological variables were assessed using a Student’s t-test or an analysis of variance test. Spearman’s rank correlation was applied to evaluate the relationship between endocan-MVD and the expression of VEGF/VEGFR2. Long-term survival of these patients was analysed using univariate and multivariate analyses. RESULTS: Positive staining of endocan was observed in most of the gastric cancer tissues (108/142) and in fewer of the normal gastric tissues. Endocan-MVD was not associated with gender or histological type (P > 0.05), while endocan-MVD was associated with tumour size, Borrmann type, tumour differentiation, tumour invasion, lymph node metastasis and TNM stage (P analysis, endocan-MVD had a positive correlation with VEGF (r = 0.167, P = 0.047) and VEGFR2 (r = 0.410, P = 0.000). The univariate analysis with a log-rank test indicated that the patients with a high level of endocan-MVD had a significantly poorer overall survival rate than those with a low level of endocan-MVD (17.9% vs 64.0%, P = 0.000). The multivariate analysis showed that a high level of endocan-MVD was a valuable prognostic factor. CONCLUSION: Endocan-MVD significantly correlates with the expression of VEGF and VEGFR2 and is a valuable prognostic factor for survival in human gastric cancer. PMID:27340359

  9. The effect of seasonal differences on prognostic factors in Turkish patients with breast cancer.

    Science.gov (United States)

    Mutlu, Hasan; Colak, Taner; Ozdoğan, Mustafa; Altuner Torun, Yasemin; Akça, Zeki

    2011-11-01

    Several studies have shown that solar light affects the prognosis of breast cancer. This effect is mostly associated with vitamin D. In-vitro studies showed that vitamin D analogs change the receptor expression in breast cancer cell lines. In our study, we studied the effect of solar light on prognostic factors of breast cancer. Patients with breast cancer from two different regions of Turkey were included in the study. These regions have different seasonal features and solar light exposures. Nine hundred and eighty-six patients were from the Akdeniz University Medical Faculty of Antalya region, and 463 patients were from the Kayseri Education and Research Hospital of Kayseri region. The Antalya region has warm climate and more solar light exposure. The Kayseri region has relatively colder climate and less solar light exposure. When histological features are considered, the estrogen and progesterone receptor expressions were higher in the Kayseri group, and a significant difference was observed for the progesterone receptor (P=0.013). No significant difference was observed for the estrogen receptor but a significant trend was observed (P=0.056). No significant difference was observed in CerbB2 expression between groups. There were significant differences for histological and nuclear grade (PAntalya group. Our study showed that, due to seasonal differences, solar light exposure leads to significant changes in prognostic factors for breast cancer. This result may be interpreted as the reflection of in-vitro findings in a clinical setting and may be accepted as one of the first such reports in the literature. PMID:21753731

  10. The Development of an Angiogenic Protein "Signature" in Ovarian Cancer Ascites as a Tool for Biologic and Prognostic Profiling.

    Science.gov (United States)

    Trachana, Sofia-Paraskevi; Pilalis, Eleftherios; Gavalas, Nikos G; Tzannis, Kimon; Papadodima, Olga; Liontos, Michalis; Rodolakis, Alexandros; Vlachos, Georgios; Thomakos, Nikolaos; Haidopoulos, Dimitrios; Lykka, Maria; Koutsoukos, Konstantinos; Kostouros, Efthimios; Terpos, Evagelos; Chatziioannou, Aristotelis; Dimopoulos, Meletios-Athanasios; Bamias, Aristotelis

    2016-01-01

    Advanced ovarian cancer (AOC) is one of the leading lethal gynecological cancers in developed countries. Based on the important role of angiogenesis in ovarian cancer oncogenesis and expansion, we hypothesized that the development of an "angiogenic signature" might be helpful in prediction of prognosis and efficacy of anti-angiogenic therapies in this disease. Sixty-nine samples of ascitic fluid- 35 from platinum sensitive and 34 from platinum resistant patients managed with cytoreductive surgery and 1st-line carboplatin-based chemotherapy- were analyzed using the Proteome ProfilerTM Human Angiogenesis Array Kit, screening for the presence of 55 soluble angiogenesis-related factors. A protein profile based on the expression of a subset of 25 factors could accurately separate resistant from sensitive patients with a success rate of approximately 90%. The protein profile corresponding to the "sensitive" subset was associated with significantly longer PFS (8 [95% Confidence Interval {CI}: 8-9] vs. 20 months [95% CI: 15-28]; Hazard ratio {HR}: 8.3, pAOC, which can be used, after appropriate validation, as a prognostic marker and a tool for selection for anti-angiogenic therapies. PMID:27258020

  11. Estimation of the extent of local prostate cancer spread according to magnetic resonance imaging findings and clinical prognostic factors

    Directory of Open Access Journals (Sweden)

    A. T. Kazymov

    2015-01-01

    Full Text Available To estimate the extent of local tumor spread is a main goal in the diagnosis of prostate cancer (PC. The value of this criterion is that its clinical stage plays a key role in choosing a treatment policy. Overestimation of the clinical stage of cancer leads to the fact that specialists refuse radical and its underestimation gives rise to its recurrence. Our trial defined criteria for the diagnostic efficiency of magnetic resonance imaging (MRI in 150 PC patients who had undergone radical prostatectomy. The findings were as follows: the diagnostic sensitivity of the method in determining the spread of the cancer beyond the organ was 76.8 %; its diagnostic specificity and accuracy were 80.2 and 78.7 %, respectively. The positive predictive value in detecting the extra-organ spread of the tumor was equal to 76.8 %; the negative predictive value was 80.2 %. A prognostic classification of a risk for locally advanced PS has been developed using the independent clinical and MRI signs found.

  12. Prognostic significance of annexin A2 and annexin A4 expression in patients with cervical cancer

    OpenAIRE

    Choi, Chel Hun; Chung, Joon-Yong; Chung, Eun Joo; Sears, John D.; Lee, Jeong-Won; Bae, Duk-Soo; Hewitt, Stephen M.

    2016-01-01

    Background The annexins (ANXs) have diverse roles in tumor development and progression, however, their clinical significance in cervical cancer has not been elucidated. The present study was to investigate the clinical significance of annexin A2 (ANXA2) and annexin A4 (ANXA4) expression in cervical cancer. Methods ANXA2 and ANXA4 immunohistochemical staining were performed on a cervical cancer tissue microarray consisting of 46 normal cervical epithelium samples and 336 cervical cancer cases ...

  13. Prognostic and Predictive Biomarkers in Colorectal Cancer. From the Preclinical Setting to Clinical Practice.

    Science.gov (United States)

    Maurel, Joan; Postigo, Antonio

    2015-01-01

    Colorectal cancer (CRC) is the second largest cause of cancer mortality in Western countries, mostly due to metastasis. Understanding the natural history and prognostic factors in patients with metastatic CRC (mCRC) is essential for the optimal design of clinical trials. The main prognostic factors currently used in clinical practice are related to tumor behavior (e.g., white blood counts, levels of lactate dehydrogenase, levels of alkaline phosphatase) disease extension (e.g., presence of extrahepatic spread, number of organs affected) and general functional status (e.g., performance status as defined by the Eastern Cooperative Oncology Group). However, these parameters are not always sufficient to establish appropriate therapeutic strategies. First-line therapy in mCRC combines conventional chemotherapy (CHT) (e.g., FOLFOX, FOLFIRI, CAPOX) with a number of agents targeted to specific signaling pathways (TA) (e.g., panitumumab and cetuximab for cases KRAS/NRAS WT, and bevacizumab). Although the response rate to this combination regime exceeds 50%, progression of the disease is almost universal and only less than 10% of patients are free of disease at 2 years. Current clinical trials with second and third line therapy include new TA, such as tyrosin-kinase receptors inhibitors (MET, HER2, IGF-1R), inhibitors of BRAF, MEK, PI3K, AKT, mTORC, NOTCH and JAK1/JAK2, immunotherapy modulators and check point inhibitors (anti-PD-L1 and anti- PD1). Despite the identification of multiple prognostic and predictive biomarkers and signatures, it is still unclear how expression of many of these biomarkers is modulated by CHT and/or TA, thus potentially affecting response to treatment. In this review we analyzed how certain biomarkers in tumor cells and microenvironment influence the response to new TA and immune-therapies strategies in mCRC pre-treated patients. PMID:26452385

  14. Polymorphisms in the mitochondrial oxidative phosphorylation chain genes as prognostic markers for colorectal cancer

    Directory of Open Access Journals (Sweden)

    Lascorz Jesus

    2012-04-01

    Full Text Available Abstract Background Currently, the TNM classification of malignant tumours based on clinicopathological staging remains the standard for colorectal cancer (CRC prognostication. Recently, we identified the mitochondrial oxidative phosphorylation chain as a consistently overrepresented category in the published gene expression profiling (GEP studies on CRC prognosis. Methods We evaluated associations of putative regulatory single nucleotide polymorphisms (SNPs in genes from the oxidative phosphorylation chain with survival and disease prognosis in 613 CRC patients from Northern Germany (PopGen cohort. Results Two SNPs in the 3′ untranslated region of UQCRB (complex III, rs7836698 and rs10504961, were associated with overall survival (HR = 0.52, 95% CI 0.32–0.85 and HR = 0.64, 95% CI 0.42–0.99, for TT carriers. These associations were restricted to the group of patients with cancer located in the colon (HR = 0.42, 95% CI 0.22–0.82 and HR = 0.46, 95% CI 0.25–0.83. Multivariate analysis indicated that both markers might act as independent prognostic markers. Additionally, the TT carriers were ~2 times more likely to develop tumours in the colon than in the rectum. Two SNPs in COX6B1 (complex IV were associated with lymph node metastasis in a dominant model (rs6510502, OR = 1.75, 95% CI 1.20–2.57; rs10420252, OR = 1.68, 95% CI 1.11–2.53; rs6510502 was associated also with distant metastasis (OR = 1.67, 95% CI 1.09–2.56 in a dominant model. Conclusions This is the first report suggesting that markers in genes from the mitochondrial oxidative chain might be prognostic factors for CRC. Additional studies replicating the presented findings are needed.

  15. Tumor budding is a strong and reproducible prognostic marker in T3N0 colorectal cancer.

    LENUS (Irish Health Repository)

    Wang, Lai Mun

    2012-02-01

    BACKGROUND: Tumor budding along the advancing front of colorectal adenocarcinoma is an early event in the metastatic process. A reproducible, prognostic budding scoring system based on outcomes in early stage colorectal cancer has not been established. DESIGN: One hundred twenty-eight T3N0M0 colorectal carcinoma patients with known outcome were identified. Tumor budding was defined as isolated tumor cells or clusters of <5 cells at the invasive tumor front. Tumor bud counts were generated in 5 regions at 200x by 2 pathologists (conventional bud count method). The median bud count per case was used to divide cases into low (median=0) and high budding (median > or =1) groups. Forty cases were reevaluated to assess reproducibility using the conventional and a novel rapid bud count method. RESULTS: Fifty-seven (45%) carcinomas had high and 71 (55%) had low budding scores. High budding was associated with an infiltrative growth pattern (P<0.0001) and lymphovascular invasion (P=0.005). Five-year cancer-specific survival was significantly poorer in high compared with low budding groups: 63% versus 91%, respectively, P<0.0001. Multivariate analysis demonstrated tumor budding to be independently prognostic (hazard ratio=4.76, P<0.001). Interobserver agreement was at least equivalent comparing the conventional to the rapid bud count methods: 87.5% agreement (kappa=0.75) versus 92.5% agreement (kappa=0.85), respectively. CONCLUSIONS: Tumor budding is a strong, reproducible, and independent prognostic marker of outcome that is easily assessed on hematoxylin and eosin slides. This may be useful for identifying the subset of T3N0M0 patients at high risk of recurrence who may benefit from adjuvant therapy.

  16. Analysis of Prognostic Factors in 541 Female Patients with Advanced Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Meina WU

    2011-03-01

    Full Text Available Background and objective As there is a sharp increase in the incidence of lung cancer in women in recent years, it has brought broad concerns with its unique clinical and epidemiological characteristics and better prognosis. The aim of this study is to analyze the clinical data of women with advanced non-small cell lung cancer (NSCLC retrospectively to explore the prognostic factors. Methods Clinical data of 541 female patients with advanced NSCLC were collected and followed up till death. The primary endpoint is overall survival (OS. SPSS 11.0 statistical analysis software was used for univariate and multivariate analysis. Results The mean age is 59 years (20 years-86 years, adenocarcinoma account for 80.2% (434/541. The median OS was 15 months (95%CI: 13.87-16.13, and 1, 2, 5-year survival rates were 58.8%, 23.7% and 3.20% respectively. Univariate analysis showed that clinical stage, ECOG score, weight loss, clinical symptoms, liver/bone/brain metastasis and received more than one chemotherapy regimen, good response to the first-line chemotherapy, EGFR-TKI targeted therapy and radiotherapy treatment were significantly correlated with the OS and survival rate (P < 0.05. Combined with multivariate analysis, weight loss before treatment, ECOG score, received EGFR-TKI targeted therapy and response to first-line chemotherapy were independent prognostic factor for survival (P < 0.05. Conclusion There is a higher percentage of adenocarcinoma in female NSCLC. Weight loss before treatment, ECOG score, EGFR-TKI targeted therapy and response to first-line chemotherapy may become independent prognostic factors for survival of female patients with advanced NSCLC.

  17. Correlation between High Resolution Dynamic MR Features and Prognostic Factors in Breast Cancer

    International Nuclear Information System (INIS)

    To correlate high resolution dynamic MR features with prognostic factors in breast cancer. One hundred and ninety-four women with invasive ductal carcinomas underwent dynamic MR imaging using T1-weighted three dimensional fast low-angle shot (3D-FLASH) sequence within two weeks prior to surgery. Morphological and kinetic MR features were determined based on the breast imaging and reporting data system (BI-RADS) MR imaging lexicon. Histological specimens were analyzed for tumor size, axillary lymph node status, histological grade, expression of estrogen receptor (ER), expression of progesterone receptor (PR), and expression of p53, c-erbB-2, and Ki-67. Correlations between the MR features and prognostic factors were determined using the Pearson x2 test, linear-by-linear association, and logistic regression analysis. By multivariate analysis, a spiculated margin was a significant, independent predictor of a lower histological grade (p < 0.001), and lower expression of Ki-67 (p = 0.007). Rim enhancement was significant, independent predictor of a higher histological grade (p < 0.001), negative expression of ER (p 0.001), negative expression of PR (p < 0.001) and a larger tumor size (p = 0.006). A washout curve may predict a higher level of Ki-67 (p = 0.05). Most of the parameters of the initial enhancement phase cannot predict the status of the prognostic factors. Only the enhancement ratio may predict a larger tumor size (p 0.05). Of the BI-RADS-MR features, a spiculated margin may predict favorable prognosis, whereas rim enhancement or washout may predict unfavorable prognosis of breast cancer

  18. Profile of prognostic factors in 1022 Indian women with early-stage breast cancer treated with breast-conserving therapy

    International Nuclear Information System (INIS)

    Purpose: The outcome of breast cancer treatment can vary in different geographic and ethnic groups. A multivariate analysis was performed for various prognostic factors in 1022 Indian women with pathologic Stage I-II breast cancer treated between 1980 and 2000 with standard breast-conserving therapy with or without systemic adjuvant therapy. Methods and Materials: At a mean follow-up of 53 months, the outcomes studied were local failure, locoregional failure, and distant failure, overall survival (OS), and disease-free survival (DFS). Results: The median pathologic tumor size was 3 cm (range, 1-5 cm), and axillary lymph node metastasis was present in 39% of women. The actuarial 5- and 10-year OS and DFS rate was 87% and 77% and 76% and 68%, respectively. Lymphovascular emboli or invasion (LVI) was the strongest independent adverse factor for all failure and survival (local failure, hazard ratio 2.85; 95% confidence interval, 1.68-4.83; OS; hazard ratio, 2.01, 95% confidence interval, 1.35-2.99). Lymph node metastasis was also an independent adverse factor for local failure, locoregional failure, distant failure, DFS, and OS (hazard ratio, 1.55, 95% confidence interval, 1.04-2.30). Age ≤40 years increased the incidence of local recurrence, and patients with inner quadrant tumors had inferior DFS. The incidence of LVI was significantly greater in women with lymph node metastases than in node-negative women (p < 0.001) and in women with Grade 3 tumors than in those with Grade 1 or 2 tumors (p = 0.001). Conclusion: In Indian women, LVI was the strongest independent prognostic factor for OS, DFS, and local recurrence, irrespective of nodal status and systemic adjuvant treatment. Although LVI may not be a contraindication for BCT, as has been proposed by certain groups, it is necessary to define its role in prospective studies in determining local and systemic treatment

  19. Independent prognostic value of eosinophil and mast cell infiltration in colorectal cancer tissue

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen; Hansen, Ulla; Christensen, Ib Jarle;

    1999-01-01

    prognostic value of individual white cell counts in the peritumoural inflammatory infiltrate in colorectal cancer was assessed. Intra-operative tumour tissue samples from 584 patients undergoing elective surgery for colorectal cancer were included. None of the patients received pre- or post......-operative adjuvant chemotherapy. Tissue blocks were cut from the periphery of the tumours and embedded in paraffin. All blocks included both tumour tissue and normal bowel tissue. Serial sections of 4 microm were analysed for tumour tissue inflammatory cell infiltration using a computer- and video......-assisted microscope, which allowed semi-automated quantification of cells within a fixed area. Total white cells and individual counts of eosinophils, neutrophils, mast cells, lymphocytes, and plasma cells were evaluated in every tumour specimen. Stratification into four groups with similar numbers of events was used...

  20. The role and prognostic significance of p53 mutation in colorectal carcinomas

    Institute of Scientific and Technical Information of China (English)

    Chen Yang Ji; DR Smith; HS Goh

    2000-01-01

    AIM To study the prognostic significance of the p53 cDNA mutation and mutant p53 protein in colorectaladenocarcinomas.METHODS p53 cDNA mutaiton was detected with RT-PCR-SSCP, and mutant p53 protein overexpressionwas detected by PAb 240 monoclonal antibody in 100 cases of colorectal adenocarcinomas. The follow-upsurvey of all patients were done within the five years after operation, and comparing with p53 cDNAmutation and mutant p53 protein overexpression for the prognostic significance of colorectaladenocarcinomas. The data is treated with SPSS computer program, Kaplan-Meier Survival Plots werecalculated and analyzed by Log-rank analysis.RESULTS Fifty-one cases of p53 eDNA mutations (51%) were found with RT-PCR-SSCP and 76 cases ofmutant p53 protein overexpression (76%) found with PAb 240 monoclonal antibody immunohistochemistrystaining in 100 cases of colorectal adenocarcinomas. There are no relationship with Dukes stage in thestatistics in p53 eDNA mutation (mutation: Dukes A 9%, B 10%, C 20%, D 12%; No mutation: A 13%, B12%, C 12%, D 12%) and mutant p53 protein overexpression (positive: Dukes A 17%, B 6%, C 27%, D16%; negative: A 5%, B 6%, C 5%, D 8%) (P<0.05). Moreover, the data show p53 cDNA mutation isassociated with mutant p53 protein overexpression (both positive 49%, single positive 29%, both negative22%) (P<0.01), p53 eDNA mutation can provide prognostic information (p53 eDNA mutation positive:alive 35, dead 16; negative: alive 42, dead 7) (P<0.05), and mutant p53 protein overexpression isambiguous and does not assess prognosis (p53 protein overexpression positive: alive 58, dead 18; negative:alive 19, dead 5) (P = 0.72) with Kaplan-Meier Survival Plots and Log-rank analysis.CONCLUSION p53 eDNA mutation is associated with mutant p53 protein overexpression (p53 eDNAmutation and mutant p53 protein overexpression both positive 49%, single positive 29%, both negative 22%)(P<0.01) and p53 eDNA mutation can provide poor prognostic information, and is the

  1. Associations of persistent organic pollutants in serum and adipose tissue with breast cancer prognostic markers.

    Science.gov (United States)

    Arrebola, J P; Fernández-Rodríguez, M; Artacho-Cordón, F; Garde, C; Perez-Carrascosa, F; Linares, I; Tovar, I; González-Alzaga, B; Expósito, J; Torne, P; Fernández, M F; Olea, N

    2016-10-01

    This study aimed to evaluate associations between exposure to a group of persistent organic pollutants, measured in both adipose tissue and serum samples from breast cancer patients, and a set of tumor prognostic markers. The study population comprised 103 breast cancer patients recruited in Granada, Southern Spain. Data for tumor prognostic markers were retrieved from hospital clinical records and socio-demographic information was gathered by questionnaire. Persistent organic pollutants were quantified by gas chromatography with electron capture detection. Exposure levels were categorized in quartiles, and associations were evaluated using unconditional logistic regression. Adipose tissue HCB concentrations were associated positively with ER and PR expression (p-trends=0.044 and 0.005, respectively) and negatively with E-Cadherin and p53 expression (p-trends=0.012 and 0.027, respectively). PCB-180 adipose tissue concentrations were positively associated with HER2 expression (p-trend=0.036). Serum PCB-138 concentrations were positively associated with ER and PR expression (p-trends=0.052 and 0.042, respectively). The risk of p53 expression was higher among women in the lowest quartile of serum PCB-138 concentrations, but no significant trend was observed (p-trend=0.161). These findings indicate that human exposure to certain persistent organic pollutants might be related to breast cancer aggressiveness. We also highlight the influence on exposure assessment of the biological matrix selected, given that both serum and adipose tissue might yield relevant information on breast cancer prognosis. PMID:27213669

  2. Large lymph node size harvested as prognostic factor in gastric cancer?

    Directory of Open Access Journals (Sweden)

    F. Espín

    2010-03-01

    Full Text Available Objective: knowledge regarding prognostic factors in gastric cancer is essential to decide on single patient management. We aim to establish the value of large lymph node size in order to improve perioperative approach. Material and methods: charts of one hundred and twenty-eight consecutive patients undergoing gastrectomy for resectable gastric cancer were reviewed between January 1996 and December 2005. Patients were split in two groups according to large lymph node size harvested, group I, lymph node size ≤ 10 mm and group II, lymph node size > 10 mm. Overall five-year survival related to cancer were analyzed as a main endpoint. Prognostic factors as TNM classification and degree of differentiation have been considered. Results: there were no differences regarding age and gender (67.4 vs. 64; p = 0.34 and 66,1 vs. 68,1%; p = 0.27, respectively. Nevertheless, a significant difference has been found according to T1-T2 of TNM stage (78.1 vs. 39.1% p = < 0.001, for N grade staging, has statistical signification for grade N0 (62.7 vs. 30.5%; p < 0.001, and for Ia and Ib stages (57.6 vs. 17.4%. Five years overall survival has a great statistical signification (p log-rank = 0.0003, however, overall survival between groups with positive lymph nodes according to lymph node size was close to signification, (p log-rank = 0.0636. Conclusions: our data indicates that large lymph node size could be a powerful predictor for overall survival in gastric cancer, when it could be evaluated in preoperative period. In our opinion lymph node size should be considered for perioperative chemotherapy schemas. Detection and staging techniques for lymph node affection acquire much more importance.

  3. Prognostic Value of MicroRNA-182 in Cancers: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Fei Wang

    2015-01-01

    Full Text Available Objective. MicroRNA-182 (miR-182 exhibits altered expression in various cancers. The aim of this study was to investigate the predictive value of miR-182 expression for cancer patient survival. Methods. Eligible studies were identified through multiple search strategies, and the hazard ratios (HRs for patient outcomes were extracted and estimated. A meta-analysis was performed to evaluate the prognostic value of miR-182. Results. In total, 14 studies were included. A high miR-182 expression level predicted a worse outcome with a pooled HR of 2.18 (95% CI: 1.53–3.11 in ten studies related to overall survival (OS, especially in Chinese populations. The results of seven studies evaluating disease-free survival/relapse-free survival/recurrence-free interval/disease-specific survival (DFS/RFS/RFI/DSS produced a pooled HR of 1.77 (95% CI: 0.91–3.43, which was not statistically significant; however, the trend was positive. When disregarding the DSS from one study, the expression of miR-182 was significantly correlated with DFS/RFS/RFI (pooled HR = 2.52, 95% CI: 1.67–3.79. Conclusions. High miR-182 expression is associated with poor OS and DFS/RFS/RFI in some types of cancers, and miR-182 may be a useful prognostic biomarker for predicting cancer prognosis. However, given the current insufficient relevant data, further clinical studies are needed.

  4. Prognostic and predictive value of circulating tumor cell analysis in colorectal cancer patients

    Directory of Open Access Journals (Sweden)

    de Albuquerque Andreia

    2012-11-01

    Full Text Available Abstract Objective The aim of this study was to assess the prognostic and predictive values of circulating tumor cell (CTC analysis in colorectal cancer patients. Patients and methods Presence of CTCs was evaluated in 60 colorectal cancer patients before systemic therapy - from which 33 patients were also evaluable for CTC analysis during the first 3 months of treatment - through immunomagnetic enrichment, using the antibodies BM7 and VU1D9 (targeting mucin 1 and EpCAM, respectively, followed by real-time RT-PCR analysis of the tumor-associated genes KRT19, MUC1, EPCAM, CEACAM5 and BIRC5. Results Patients were stratified into groups according to CTC detection (CTC negative, when all marker genes were negative; and CTC positive when at least one of the marker genes was positive. Patients with CTC positivity at baseline had a significant shorter median progression-free survival (median PFS 181.0 days; 95% CI 146.9-215.1 compared with patients with no CTCs (median PFS 329.0 days; 95% CI 299.6-358.4; Log-rank P Conclusion The present study provides evidence of a strong correlation between CTC detection and radiographic disease progression in patients receiving chemotherapy for colorectal cancer. Our results suggest that in addition to the current prognostic factors, CTC analysis represent a potential complementary tool for prediction of colorectal cancer patients’ outcome. Moreover, the present test allows for molecular characterization of CTCs, which may be of relevance to the creation of personalized therapies.

  5. Molecular classification and prognostication of 300 node-negative breast cancer cases: A tertiary care experience

    Science.gov (United States)

    Shemin, K. M. Zuhara; Smitha, N. V.; Jojo, Annie; Vijaykumar, D. K.

    2015-01-01

    Background: The proportion of node-negative breast cancer patients has been increasing with improvement of diagnostic modalities and early detection. However, there is a 20–30% recurrence in node-negative breast cancers. Determining who should receive adjuvant therapy is challenging, as the majority are cured by surgery alone. Hence, it requires further stratification using additional prognostic and predictive factors. Subjects and Methods: Ours is a single institution retrospective study, on 300 node-negative breast cancer cases, who underwent primary surgery over a period of 7 years (2005–2011). We excluded all cases who took NACT. Prognostic factors of age, size, lymphovascular emboli, estrogen receptor (ER), progesterone receptor (PR), HER2neu Ki-67, grade and molecular classification were analyzed with respect to those with and without early events (recurrence, metastases or second malignancy, death) using-Pearson Chi-square method and logistic regression method for statistical analysis. Results: Majority belonged to the age group of 50–70 years. On univariate analysis, size >5 cm (P = 0.03) and ER negativity had significant association (P = 0.05) for early failures; PR negativity and lymphovascular emboli (LVE) had borderline significance (P = 0.07). Multivariate analysis showed size >5 cm to be significant (P = 0.04) and LVE positivity showed borderline significant association (P = 0.07) with early failures. About 62% belonged to luminal category followed by basal-like (25%) in molecular classification. Conclusions: ER negativity, PR negativity, LVE/lymphovascular invasion positivity and size >5 cm (T3 and T4) are associated with poor prognosis in node-negative breast cancers. PMID:26981506

  6. Molecular classification and prognostication of 300 node-negative breast cancer cases: A tertiary care experience

    Directory of Open Access Journals (Sweden)

    K M Zuhara Shemin

    2015-01-01

    Full Text Available Background: The proportion of node-negative breast cancer patients has been increasing with improvement of diagnostic modalities and early detection. However, there is a 20-30% recurrence in node-negative breast cancers. Determining who should receive adjuvant therapy is challenging, as the majority are cured by surgery alone. Hence, it requires further stratification using additional prognostic and predictive factors. Subjects and Methods: Ours is a single institution retrospective study, on 300 node-negative breast cancer cases, who underwent primary surgery over a period of 7 years (2005-2011. We excluded all cases who took NACT. Prognostic factors of age, size, lymphovascular emboli, estrogen receptor (ER, progesterone receptor (PR, HER2neu Ki-67, grade and molecular classification were analyzed with respect to those with and without early events (recurrence, metastases or second malignancy, death using-Pearson Chi-square method and logistic regression method for statistical analysis. Results: Majority belonged to the age group of 50-70 years. On univariate analysis, size >5 cm (P = 0.03 and ER negativity had significant association (P = 0.05 for early failures; PR negativity and lymphovascular emboli (LVE had borderline significance (P = 0.07. Multivariate analysis showed size >5 cm to be significant (P = 0.04 and LVE positivity showed borderline significant association (P = 0.07 with early failures. About 62% belonged to luminal category followed by basal-like (25% in molecular classification. Conclusions: ER negativity, PR negativity, LVE/lymphovascular invasion positivity and size >5 cm (T3 and T4 are associated with poor prognosis in node-negative breast cancers.

  7. SERPINB3 in the chicken model of ovarian cancer: a prognostic factor for platinum resistance and survival in patients with epithelial ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Whasun Lim

    Full Text Available Serine protease inhibitors (SERPINs appear to be ubiquitously expressed in a variety of species and play important roles in pivotal physiological processes such as angiogenesis, immune responses, blood coagulation and fibronolysis. Of these, squamous cell carcinoma antigen 1 (SCCA1, also known as a SERPINB3, was first identified in squamous cell carcinoma tissue from the cervix of women. However, there is little known about the SERPINB3 expression in human epithelial ovarian cancer (EOC. Therefore, in the present study, we investigated the functional role of SERPINB3 gene in human EOC using chickens, the most relevant animal model. In 136 chickens, EOC was found in 10 (7.4%. SERPINB3 mRNA was induced in cancerous, but not normal ovaries of chickens (P<0.01, and it was abundant only in the glandular epithelium of cancerous ovaries of chickens. Further, several microRNAs, specifically miR-101, miR-1668 and miR-1681 were discovered to influence SERPINB3 expression via its 3'-UTR which suggests that post-transcriptional regulation influences SERPINB3 expression in chickens. SERPINB3 protein was localized predominantly to the glandular epithelium in cancerous ovaries of chickens, and it was abundant in the nucleus of both chicken and human ovarian cancer cell lines. In 109 human patients with EOC, 15 (13.8%, 66 (60.6% and 28 (25.7% patients showed weak, moderate and strong expression of SERPINB3 protein, respectively. Strong expression of SERPINB3 protein was a prognostic factor for platinum resistance (adjusted OR; odds ratio, 5.94; 95% Confidence Limits, 1.21-29.15, and for poor progression-free survival (PFS; adjusted HR; hazard ratio, 2.07; 95% CI; confidence interval, 1.03-4.41. Therefore, SERPINB3 may play an important role in ovarian carcinogenesis and be a novel biomarker for predicting platinum resistance and a poor prognosis for survival in patients with EOC.

  8. Assessment of prognostic significance of cytoplasmic survivin expression in advanced oesophageal cancer.

    Directory of Open Access Journals (Sweden)

    G Wallner

    2004-10-01

    Full Text Available Survivin is a member of the family of proteins, which inhibit apoptosis (inhibitor of apoptosis proteins - IAP. Expression of survivin was found in colorectal cancer, neuroblastoma, bladder cancer, non-small cell lung cancer, and breast cancer. There is some recent data indicating the correlation of poor prognosis and worse response to chemotherapy in patients with oesophageal squamous cell carcinoma (OSCC expressing survivin. The aim of the present study was to assess survivin expression in cancerous tissue of patients with advanced OSCC and to test the potential correlation between survivin expression and clinicopathological data. Forty two patients (mean age 58.36+/-8.97 yrs, who were oesophagectomised due to squamous cell carcinoma of the thoracic oesophagus between 1998 and 2000, were retrospectively analysed. Cytoplasmic survivin expression, examined immunohistochemically, was found in 35 (83.33% cases. No statistically significant correlation between survivin expression in the tumour and patients' gender, TNM stage, or vascular involvement was noted. The mean survival of patients with cytoplasmic survivin expression (17.81+/-5.51 months was not statistically different to those with negative survivin staining (16+/-6.28 months as assessed by Mantel-Cox test (p=0.49. Univariate regression analysis revealed UICC staging as the only predictor of survival in the analysed group (p<0.05. These results indicate that the cytoplasmic survivin expression does not seem to be the prognostic factor in advanced cases of OSCC.

  9. Are salivary amylase and pH – Prognostic indicators of cancers?

    Science.gov (United States)

    Ramya, Atmakuri Shanmukha; Uppala, Divya; Majumdar, Sumit; Surekha, Ch.; Deepak, K.G.K.

    2015-01-01

    Background Saliva, “Mirror of body's health” has long been of particular interest as a substitute for blood for disease diagnosis and monitoring. The radiation effects on salivary glands are of particular interest in which salivary amylase is a good indicator of salivary glands function. Thus, estimation of these parameters represents a reasonable approach in evaluation of patient's risk for disease occurrence, intensity and prognosis. Aim of study To evaluate and compare the pH and amylase levels in saliva of cancer patients prior to treatment, patients during treatment. Materials and methods Saliva samples of 90 individuals were taken which were divided into 3 groups - 30 individuals without cancer, 30 cancer patients prior treatment and 30 cancer patients during treatment. Materials used were pH strips and pH meter, Salivary Amylase assay. Results Statistical analysis – ANOVA with post-hoc Tukey's test. 1) Significant decrease in salivary amylase levels – in cancer patients, during treatment when compared to others. 2) Significant decrease in salivary pH levels in newly diagnosed cancer patients prior to treatment. Conclusion To conclude, pH strips and pH meter showed to be a useful tool in the measurement of pH of saliva in individuals with and without cancer. This study showed that cancer patients without treatment have a lower pH of saliva. Treatment increased the pH of the saliva to a more alkaline level whereas amylase levels decreased in those subjects. Therefore those parameters can be an area of further research with an increased sample size, which in-turn may help in opening the doors for new dimension in non invasive prognostic markers. PMID:26258019

  10. Prognostic Effect of Pretreatment Serum Carcinoembryonic Antigen Level

    OpenAIRE

    Kim, Chang Hyun; Lee, Soo Young; Kim, Hyeong Rok; Kim, Young Jin

    2015-01-01

    Abstract Many studies have reported the prognostic value of pretreatment serum carcinoembryonic antigen (pre-CEA) levels on colorectal cancer outcomes. However, controversy remains concerning the significance of pre-CEA levels in patients with rectal cancer treated with neoadjuvant chemoradiotherapy (CRT). Our aim in this study was to investigate the prognostic role of the pre-CEA level in patients with locally advanced rectal cancer undergoing neoadjuvant CRT followed by total mesorectal exc...

  11. Cancer testis antigens and NY-BR-1 expression in primary breast cancer: prognostic and therapeutic implications

    International Nuclear Information System (INIS)

    Cancer–testis antigens (CTA) comprise a family of proteins, which are physiologically expressed in adult human tissues solely in testicular germ cells and occasionally placenta. However, CTA expression has been reported in various malignancies. CTAs have been identified by their ability to elicit autologous cellular and or serological immune responses, and are considered potential targets for cancer immunotherapy. The breast differentiation antigen NY-BR-1, expressed specifically in normal and malignant breast tissue, has also immunogenic properties. Here we evaluated the expression patterns of CTAs and NY-BR-1 in breast cancer in correlation to clinico-pathological parameters in order to determine their possible impact as prognostic factors. The reactivity pattern of various mAbs (6C1, MA454, M3H67, 57B, E978, GAGE #26 and NY-BR-1 #5) were assessed by immunohistochemistry in a tissue micro array series of 210 randomly selected primary invasive breast cancers in order to study the diversity of different CTAs (e.g. MAGE-A, NY-ESO-1, GAGE) and NY-BR-1. These expression data were correlated to clinico-pathological parameters and outcome data including disease-free and overall survival. Expression of at least one CTA was detectable in the cytoplasm of tumor cells in 37.2% of the cases. NY-BR-1 expression was found in 46.6% of tumors, respectively. Overall, CTA expression seemed to be linked to adverse prognosis and M3H67 immunoreactivity specifically was significantly correlated to shorter overall and disease-free survival (p=0.000 and 0.024, respectively). Our findings suggest that M3H67 immunoreactivity could serve as potential prognostic marker in primary breast cancer patients. The exclusive expression of CTAs in tumor tissues as well as the frequent expression of NY-BR-1 could define new targets for specific breast cancer therapies

  12. The potential prognostic value of connexin 26 and 46 expression in neoadjuvant-treated breast cancer

    Directory of Open Access Journals (Sweden)

    Teleki Ivett

    2013-02-01

    Full Text Available Abstract Background Several classification systems are available to assess pathological response to neoadjuvant chemotherapy in breast cancer, but reliable biomarkers to predict the efficiency of primary systemic therapy (PST are still missing. Deregulation of gap junction channel forming connexins (Cx has been implicated in carcinogenesis and tumour progression through loss of cell cycle control. In this study we correlated Cx expression and cell proliferation with disease survival and pathological response to neoadjuvant chemotherapy in breast cancers using existing classification systems. Methods The expression of Cx26, Cx32, Cx43, Cx46 and Ki67 was evaluated in 96 breast cancer patients prior to and after neoadjuvant chemotherapy using duplicate cores in tissue microarrays (TMA. Cx plaques of Results In our cohort dominated by hormone receptor (ER/PR positive and HER2 negative cases, only the CPS-EG classification showed prognostic relevance: cases with scores 1–2 had significantly better overall survival (p=0.015 than cases with scores 3–5. Pre-chemotherapy Cx43 expression correlated positively with hormone receptor status both before and after chemotherapy and had a negative correlation with HER2 expression pre-chemotherapy. There was a positive correlation between Cx32 and HER2 expression pre-chemotherapy and between Cx32 and Ki67 expression post-chemotherapy. A negative correlation was found between post-chemotherapy Cx46 and Ki67 expression. Decreased post-chemotherapy Cx26 expression (20% pre- and post-chemotherapy correlated with significantly better survival in the intermediate prognostic subgroups of EWGBSP TR2b (ppre-chemo=0.006; Sataloff TB (ppre-chemo=0.005; ppost-chemo=0.029 and in Miller-Payne G3 (ppre-chemo=0.002; ppost-chemo=0.012 classifications. Pre-chemotherapy, Cx46 expression was the only marker that correlated with overall survival within these subgroups. Conclusion Our results suggest that Cx46 and Cx26 expression

  13. The potential prognostic value of connexin 26 and 46 expression in neoadjuvant-treated breast cancer

    International Nuclear Information System (INIS)

    Several classification systems are available to assess pathological response to neoadjuvant chemotherapy in breast cancer, but reliable biomarkers to predict the efficiency of primary systemic therapy (PST) are still missing. Deregulation of gap junction channel forming connexins (Cx) has been implicated in carcinogenesis and tumour progression through loss of cell cycle control. In this study we correlated Cx expression and cell proliferation with disease survival and pathological response to neoadjuvant chemotherapy in breast cancers using existing classification systems. The expression of Cx26, Cx32, Cx43, Cx46 and Ki67 was evaluated in 96 breast cancer patients prior to and after neoadjuvant chemotherapy using duplicate cores in tissue microarrays (TMA). Cx plaques of <1μm were detected with multilayer, multichannel fluorescence digital microscopy. Current classifications to assess residual tumour burden after primary systemic therapy included the EWGBSP, CPS-EG, Miller-Payne, Sataloff and NSABP systems. In our cohort dominated by hormone receptor (ER/PR) positive and HER2 negative cases, only the CPS-EG classification showed prognostic relevance: cases with scores 1–2 had significantly better overall survival (p=0.015) than cases with scores 3–5. Pre-chemotherapy Cx43 expression correlated positively with hormone receptor status both before and after chemotherapy and had a negative correlation with HER2 expression pre-chemotherapy. There was a positive correlation between Cx32 and HER2 expression pre-chemotherapy and between Cx32 and Ki67 expression post-chemotherapy. A negative correlation was found between post-chemotherapy Cx46 and Ki67 expression. Decreased post-chemotherapy Cx26 expression (<5%) statistically correlated with better overall survival (p=0.011). Moderate or higher Cx46 expression (>20%) pre- and post-chemotherapy correlated with significantly better survival in the intermediate prognostic subgroups of EWGBSP TR2b (ppre-chemo=0

  14. High apoptotic index correlates to p21 and p27 expression indicating a favorable outcome of primary breast cancer patients, but lacking prognostic significance in multivariate analysis.

    Science.gov (United States)

    Schöndorf, Thomas; Göhring, Uwe-Jochen; Becker, Martina; Hoopmann, Markus; Schmidt, Torsten; Rützel, Sabine; Rein, Daniel T; Ulrich, Uwe; Fechteler, Roland; Bersch, Alexander; Mallmann, Peter; Valter, Markus M

    2004-01-01

    This study was performed in order to investigate the role of the apoptotic index (AI) as a prediction parameter for the prognosis of patients with primary breast cancer. AI was determined by DNA fragmentation on 298 primary breast cancer samples and compared to clinically established breast cancer parameters. Additionally, we determined the expression of functional parameters including proliferating cell nuclear antigen, p21waf and p27kip by immunohistochemistry. The mean AI was found to be 11.9% (range, 0-90%). 189 tumors (63.4%) were negative for apoptosis, while 109 tissue samples (36.6%) were apoptotic with >5% positive cells. Using univariate analysis (chi2 test), the AI did not show any significant correlation to one of the established prognostic parameters of primary breast cancer (p > 0.05). In contrast, we found a significant positive correlation to the expression of the cell cycle inhibitors p21waf (p = 0.04) and p27kip (p = 0.024). During the clinical follow-up (median observation time for disease-free survival 87 months), several clinically established prognostic parameters including menopausal status, nodal status, tumor size, tumor grade, and hormone receptor expression could be confirmed and were analyzed with respect to the AI in the tumor. Furthermore, AI displayed a significant positive correlation to disease-free survival using Kaplan-Meier survival analysis (log-rank test, p = 0.04). However, AI lost its prognostic significance in multivariate analysis based on the Cox proportional hazard model (relative risk 0.8, confidence interval 0.52-1.33, p = 0.44). Our data indicate that high apoptotic rates in cancer tissues are indicative of a favorable patient outcome. However, the AI was not an independent factor. The study provides indirect evidence that this process may involve cell cycle inhibitors physiologically. PMID:15263811

  15. Anti-α-enolase is a prognostic marker in postoperative lung cancer patients

    OpenAIRE

    Hsiao, Kuan-Chung; Shih, Neng-Yao; Chu, Pei-Yi; Hung, Yi-Mei; Liao, Jia-Yi; Chou, Shao-Wen; Yang, Yi-Yuan; Chang, Gee-Chen; Liu, Ko-Jiunn

    2015-01-01

    Our previous studies suggest that antibodies against ENO1 (anti-ENO1 Ab) have a protective role in patients with non-small cell lung carcinoma. In this study, we evaluated the prognostic value of anti-ENO1 Ab levels in non-small cell lung carcinoma patients undergoing surgery. Circulating levels of anti-ENO1 Ab were assessed in 85 non-small cell lung carcinoma patients before and after surgery, and were correlated with clinical outcome. After surgery, patients with a higher increase of anti-E...

  16. Prognostic impact of ReTURB in high grade T1 primary bladder cancer

    Directory of Open Access Journals (Sweden)

    Roberto Sanseverino

    2016-07-01

    Full Text Available Purpose: To evaluate whether pathological outcomes of ReTURB have a prognostic impact on recurrence and progression of primitive T1HG bladder cancer. Material and methods: Patients affected by primitive T1HG TCC of bladder underwent restaging TURB (ReTURB. Patients with muscle invasive disease at ReTURB underwent radical cystectomy; those with non-muscle invasive residual (NMI-RT and those with no residual tumour (NRT received an intravesical BCG therapy. We compared recurrence and progression in NMIRT patients and NRT patients at restaging TURB. Patients were followed every 3-6 months with cystoscopy and urine cytology. Results: 212 patients were enrolled in the study. At ReTURB, residual cancer was detected in 92 of 196 (46.9% valuable patients: 14.3% of these were upstaged to T2. At follow up of 26.3 ± 22.8 months, there were differences in recurrence and progression rates between NRT and NMIRT patients: 26.9% and 45.3% (p < 0.001, 10.6% and 23.4% (p 0.03, respectively. Recurrence-free and progression-free survivals were significantly higher in NRT compared to NMIRT patients: 73.1% and 54.7% (p < 0.001, 89.4% and 76.6 (p 0.03, respectively. Conclusions: ReTURB allows to identify a considerable number of residual and understaged cancer. Patients with NMIRT on ReTURB have worse prognosis than those with NRT in terms of recurrence and progression free survival. These outcomes seem to suggest a prognostic impact of findings on ReTURB that could be a valid tool in management of high grade T1 TCC.

  17. Liver metastasis is the only independent prognostic factor in AFP-producing gastric cancer

    Directory of Open Access Journals (Sweden)

    Shoji Hirajima

    2013-01-01

    Full Text Available AIM: To investigate differences between common gastric cancer and α-fetoprotein (AFP-producing gastric cancer according to the presence or absence of liver metastasis. METHODS: Between 1997 and 2011, 1299 patients underwent gastrectomy for gastric cancer (GC at our institute and their hospital records were reviewed retrospectively. Patients were immunohistochemically divided into two groups: 23 patients (1.8% with AFP-producing GC and 1276 patients (98.2% without it. RESULTS: AFP-producing GC patients had a significantly higher incidence of deeper tumors, venous invasion, lymphatic invasion, lymph node metastasis, and liver metastasis and a poorer prognosis (P < 0.005 than those without AFP-producing GC. However, multivariate analysis revealed that AFP-positivity was not an independent prognostic factor. The prognosis of AFP-producing GC was similar to that of AFP-non producing GC according to the presence or absence of liver metastasis. Concerning recurrence, 47.8% of patients (11/23 with AFP-producing GC and 20.0% of patients (256/1276 without AFP-producing GC exhibited recurrence. Liver metastasis [90.9% (10/11] was the most prevalent in AFP-producing GC patients. Multivariate analysis revealed that liver metastasis was the only independent prognostic factor in AFP-producing GC (HR = 17.6, 95%CI: 2.1-147.1; P = 0.0081. CONCLUSION: AFP-producing GC is similar to common GC without liver metastasis, which should be specifically targeted in an effort to improve the prognosis of AFP-producing GC patients.

  18. A laboratory prognostic index model for patients with advanced non-small cell lung cancer.

    Directory of Open Access Journals (Sweden)

    Arife Ulas

    Full Text Available We aimed to establish a laboratory prognostic index (LPI in advanced non-small cell lung cancer (NSCLC patients based on hematologic and biochemical parameters and to analyze the predictive value of LPI on NSCLC survival.The study retrospectively reviewed 462 patients with advanced NSCLC diagnosed between 2000 and 2010 in a single institution. We developed an LPI that included serum levels of white blood cells (WBC, lactate dehydrogenase (LDH, albumin, calcium, and alkaline phosphatase (ALP, based on the results of a Cox regression analysis. The patients were classified into 3 LPI groups as follows: LPI 0: normal; LPI 1: one abnormal laboratory finding; and LPI 2: at least 2 abnormal laboratory findings.The median follow up period was 44 months; the median overall survival (OS and median progression-free survival (PFS were 11 and 6 months, respectively. A multivariate analysis revealed that the following could be used as independent prognostic factors: an Eastern Cooperative Oncology Group performance status score (ECOG PS ≥2, a high LDH level, serum albumin 10.5 g/dL, number of metastases>2, presence of liver metastases, malignant pleural effusion, or receiving chemotherapy ≥4 cycles. The 1-year OS rates according to LPI 0, LPI 1, and LPI 2 were 54%, 34%, and 17% (p<0.001, respectively and 6-month PFS rates were 44%, 27%, and 15% (p<0.001, respectively. The LPI was a significant predictor for OS (Hazard Ratio (HR: 1.41; 1.05-1.88, p<0.001 and PFS (HR: 1.48; 1.14-1.93, p<0.001.An LPI is an inexpensive, easily accessible and independent prognostic index for advanced NSCLC and may be helpful in making individualized treatment plans and predicting survival rates when combined with clinical parameters.

  19. Stratification and prognostic relevance of Jass’s molecular classification of colorectal cancer

    Directory of Open Access Journals (Sweden)

    Inti eZlobec

    2012-02-01

    Full Text Available Background: The current proposed model of colorectal tumorigenesis is based primarily on CpG island methylator phenotype (CIMP, microsatellite instability (MSI, KRAS, BRAF, and methylation status of 0-6-Methylguanine DNA Methyltransferase (MGMT and classifies tumors into 5 subgroups. The aim of this study is to validate this molecular classification and test its prognostic relevance. Methods: 302 patients were included in this study. Molecular analysis was performed for 5 CIMP-related promoters (CRABP1, MLH1, p16INK4a, CACNA1G, NEUROG1, MGMT, MSI, KRAS and BRAF. Tumors were CIMP-high or CIMP-low if ≥4 and 1-3 promoters were methylated, respectively. Results: CIMP-high, CIMP-low and CIMP–negative were found in 7.1%, 43% and 49.9% cases, respectively. 123 tumors (41% could not be classified into any one of the proposed molecular subgroups, including 107 CIMP-low, 14 CIMP-high and 2 CIMP-negative cases. The 10-year survival rate for CIMP-high patients (22.6% (95%CI: 7-43 was significantly lower than for CIMP-low or CIMP-negative (p=0.0295. Only the combined analysis of BRAF and CIMP (negative versus low/high led to distinct prognostic subgroups. Conclusion: Although CIMP status has an effect on outcome, our results underline the need for standardized definitions of low- and high-level CIMP, which clearly hinders an effective prognostic and molecular classification of colorectal cancer.

  20. A retrospective comparative exploratory study on two Methylentetrahydrofolate Reductase (MTHFR) polymorphisms in esophagogastric cancer: the A1298C MTHFR polymorphism is an independent prognostic factor only in neoadjuvantly treated gastric cancer patients

    International Nuclear Information System (INIS)

    Methylentetrahydrofolate reductase (MTHFR) plays a major role in folate metabolism and consequently could be an important factor for the efficacy of a treatment with 5-fluorouracil. Our aim was to evaluate the prognostic and predictive value of two well characterized constitutional MTHFR gene polymorphisms for primarily resected and neoadjuvantly treated esophagogastric adenocarcinomas. 569 patients from two centers were analyzed (gastric cancer: 218, carcinoma of the esophagogastric junction (AEG II, III): 208 and esophagus (AEG I): 143). 369 patients received neoadjuvant chemotherapy followed by surgery, 200 patients were resected without preoperative treatment. The MTHFR C677T and A1298C polymorphisms were determined in DNA from peripheral blood lymphozytes. Associations with prognosis, response and clinicopathological factors were analyzed retrospectively within a prospective database (chi-square, log-rank, cox regression). Only the MTHFR A1298C polymorphisms had prognostic relevance in neoadjuvantly treated patients but it was not a predictor for response to neoadjuvant chemotherapy. The AC genotype of the MTHFR A1298C polymorphisms was significantly associated with worse outcome (p = 0.02, HR 1.47 (1.06-2.04). If neoadjuvantly treated patients were analyzed based on their tumor localization, the AC genotype of the MTHFR A1298C polymorphisms was a significant negative prognostic factor in patients with gastric cancer according to UICC 6th edition (gastric cancer including AEG type II, III: HR 2.0, 95% CI 1.3-2.0, p = 0.001) and 7th edition (gastric cancer without AEG II, III: HR 2.8, 95% CI 1.5-5.7, p = 0.003), not for AEG I. For both definitions of gastric cancer the AC genotype was confirmed as an independent negative prognostic factor in cox regression analysis. In primarily resected patients neither the MTHFR A1298C nor the MTHFR C677T polymorphisms had prognostic impact. The MTHFR A1298C polymorphisms was an independent prognostic factor in patients with

  1. Predictive and Prognostic Protein Biomarkers in Epithelial Ovarian Cancer: Recommendation for Future Studies

    International Nuclear Information System (INIS)

    Epithelial ovarian cancer is the most lethal gynecological malignancy. Due to its lack of symptoms, this disease is diagnosed at an advanced stage when the cancer has already spread to secondary sites. While initial rates of response to first treatment is >80%, the overall survival rate of patients is extremely low, mainly due to development of drug resistance. To date, there are no reliable clinical factors that can properly stratify patients for suitable chemotherapy strategies. Clinical parameters such as disease stage, tumor grade and residual disease, although helpful in the management of patients after their initial surgery to establish the first line of treatment, are not efficient enough. Accordingly, reliable markers that are independent and complementary to clinical parameters are needed for a better management of these patients. For several years, efforts to identify prognostic factors have focused on molecular markers, with a large number having been investigated. This review aims to present a summary of the recent advances in the identification of molecular biomarkers in ovarian cancer patient tissues, as well as an overview of the need and importance of molecular markers for personalized medicine in ovarian cancer

  2. Predictive and Prognostic Protein Biomarkers in Epithelial Ovarian Cancer: Recommendation for Future Studies

    Directory of Open Access Journals (Sweden)

    Cécile Le Page

    2010-05-01

    Full Text Available Epithelial ovarian cancer is the most lethal gynecological malignancy. Due to its lack of symptoms, this disease is diagnosed at an advanced stage when the cancer has already spread to secondary sites. While initial rates of response to first treatment is >80%, the overall survival rate of patients is extremely low, mainly due to development of drug resistance. To date, there are no reliable clinical factors that can properly stratify patients for suitable chemotherapy strategies. Clinical parameters such as disease stage, tumor grade and residual disease, although helpful in the management of patients after their initial surgery to establish the first line of treatment, are not efficient enough. Accordingly, reliable markers that are independent and complementary to clinical parameters are needed for a better management of these patients. For several years, efforts to identify prognostic factors have focused on molecular markers, with a large number having been investigated. This review aims to present a summary of the recent advances in the identification of molecular biomarkers in ovarian cancer patient tissues, as well as an overview of the need and importance of molecular markers for personalized medicine in ovarian cancer.

  3. Prognostic and predictive values of long non-coding RNA LINC00472 in breast cancer.

    Science.gov (United States)

    Shen, Yi; Katsaros, Dionyssios; Loo, Lenora W M; Hernandez, Brenda Y; Chong, Clayton; Canuto, Emilie Marion; Biglia, Nicoletta; Lu, Lingeng; Risch, Harvey; Chu, Wen-Ming; Yu, Herbert

    2015-04-20

    LINC00472 is a novel long intergenic non-coding RNA. We evaluated LINC00472 expression in breast tumor samples using RT-qPCR, performed a meta-analysis of over 20 microarray datasets from the Gene Expression Omnibus (GEO) database, and investigated the effect of LINC00472 expression on cell proliferation and migration in breast cancer cells transfected with a LINC00472-expressing vector. Our qPCR results showed that high LINC00472 expression was associated with less aggressive breast tumors and more favorable disease outcomes. Patients with high expression of LINC00472 had significantly reduced risk of relapse and death compared to those with low expression. Patients with high LINC00472 expression also had better responses to adjuvant chemo- or hormonal therapy than did patients with low expression. Results of meta-analysis on multiple studies from the GEO database were in agreement with the findings of our study. High LINC00472 was also associated with favorable molecular subtypes, Luminal A or normal-like tumors. Cell culture experiments showed that up-regulation of LINC00472 expression could suppress breast cancer cell proliferation and migration. Collectively, our clinical and in vitro studies suggest that LINC00472 is a tumor suppressor in breast cancer. Evaluating this long non-coding RNA in breast tumors may have prognostic and predictive value in the clinical management of breast cancer. PMID:25865225

  4. Regulatory T Cells in Colorectal Cancer: From Biology to Prognostic Relevance

    International Nuclear Information System (INIS)

    Regulatory T cells (Tregs) were initially described as “suppressive” lymphocytes in the 1980s. However, it took almost 20 years until the concept of Treg-mediated immune control in its present form was finally established. Tregs are obligatory for self-tolerance and defects within their population lead to severe autoimmune disorders. On the other hand Tregs may promote tolerance for tumor antigens and even hamper efforts to overcome it. Intratumoral and systemic accumulation of Tregs has been observed in various types of cancer and is often linked to worse disease course and outcome. Increase of circulating Tregs, as well as their presence in mesenteric lymph nodes and tumor tissue of patients with colorectal cancer de facto suggests a strong involvement of Tregs in the antitumor control. This review will focus on the Treg biology in view of colorectal cancer, means of Treg accumulation and the controversies regarding their prognostic significance. In addition, a concise overview will be given on how Tregs and their function can be targeted in cancer patients in order to bolster an inherent immune response and/or increase the efficacy of immunotherapeutic approaches

  5. Regulatory T Cells in Colorectal Cancer: From Biology to Prognostic Relevance

    Energy Technology Data Exchange (ETDEWEB)

    Mougiakakos, Dimitrios [Department of Oncology and Pathology, Immune and Gene Therapy Unit, Cancer Centre Karolinska, CCK R8:01, 17176 Stockholm (Sweden)

    2011-03-29

    Regulatory T cells (Tregs) were initially described as “suppressive” lymphocytes in the 1980s. However, it took almost 20 years until the concept of Treg-mediated immune control in its present form was finally established. Tregs are obligatory for self-tolerance and defects within their population lead to severe autoimmune disorders. On the other hand Tregs may promote tolerance for tumor antigens and even hamper efforts to overcome it. Intratumoral and systemic accumulation of Tregs has been observed in various types of cancer and is often linked to worse disease course and outcome. Increase of circulating Tregs, as well as their presence in mesenteric lymph nodes and tumor tissue of patients with colorectal cancer de facto suggests a strong involvement of Tregs in the antitumor control. This review will focus on the Treg biology in view of colorectal cancer, means of Treg accumulation and the controversies regarding their prognostic significance. In addition, a concise overview will be given on how Tregs and their function can be targeted in cancer patients in order to bolster an inherent immune response and/or increase the efficacy of immunotherapeutic approaches.

  6. Prognostic implications of carboxyl-terminus of Hsc70 interacting protein and lysyl-oxidase expression in human breast cancer

    Directory of Open Access Journals (Sweden)

    Patani Neill

    2010-01-01

    Full Text Available Background: Ubiquitin modification of proteins influences cellular processes relevant to carcinogenesis. CHIP (carboxyl-terminus of Hsc70-interacting protein is a chaperone-dependent E3 ubiquitin ligase, regulating the stability of heat shock protein 90 (HSP90 interacting proteins. CHIP is implicated in the modulation of estrogen receptor (ESR1 and Her-2/neu (ERBB2 stability. LOX (lysyl-oxidase serves intracellular roles and catalyses the cross-linking of extracellular matrix (ECM collagens and elastin. LOX expression is altered in human malignancies and their peri-tumoral stroma. However, paradoxical roles are reported. In this study, the level of mRNA expression of CHIP and LOX were assessed in normal and malignant breast tissue and correlated with clinico-pathological parameters. Materials and Methods: Breast cancer (BC tissues (n = 127 and normal tissues (n = 33 underwent RNA extraction and reverse transcription; transcript levels were determined using real-time quantitative PCR and normalized against CK-19. Transcript levels were analyzed against TNM stage, nodal involvement, tumor grade and clinical outcome over a ten-year follow-up period. Results: CHIP expression decreased with increasing Nottingham Prognostic Index (NPI: NPI-1 vs. NPI-3 (12.2 vs. 0.2, P = 0.0264, NPI-2 vs. NPI-3 (3 vs. 0.2, P = 0.0275. CHIP expression decreased with increasing TNM stage: TNM-1 vs. TNM-2 (12 vs. 0, P = 0.0639, TNM-1 vs. TNM-2-4 (12 vs. 0, P = 0.0434. Lower transcript levels were associated with increasing tumor grade: grade 1 vs. grade 3 (17.7 vs. 0.3, P = 0.0266, grade 2 vs. grade 3 (5 vs. 0.3, P = 0.0454. The overall survival (OS for tumors classified as ′low-level expression′, was poorer than those with ′high-level expression′ (118.1 vs. 152.3 months, P = 0.039. LOX expression decreased with increasing NPI: NPI-1 vs. NPI-2 (3 vs. 0, P = 0.0301 and TNM stage: TNM-1 = 3854639, TNM-2 = 908900, TNM-3 = 329, TNM-4 = 1.232 (P = NS. Conclusion: CHIP

  7. The prognostic value of positron emission tomography in non-small cell lung cancer : Analysis of 266 cases

    NARCIS (Netherlands)

    Kramer, H.; Post, W.J.; Pruim, J.; Groen, H.J.M.

    2006-01-01

    Positron emission tomography (PET) is more accurate than computed tomography (CT) in the staging of non-small cell lung cancer (NSCLC). We analyzed the prognostic value of PET for survival in NSCLC patients. Methods: Consecutive patients with proven NSCLC with PET for staging were selected. Staging

  8. Circulating vascular endothelial growth factor six months after primary surgery as a prognostic marker in patients with colorectal cancer

    DEFF Research Database (Denmark)

    Werther, Kim; Sørensen, Steen; Christensen, Ib Jarle; Nielsen, Hans Jørgen

    2003-01-01

    High preoperative circulating vascular endothelial growth factor (VEGF) is predictive of poor prognosis in patients with colorectal cancer (CRC). However, postoperative circulating VEGF has not yet been evaluated as a prognostic marker in CRC patients. In 318 consecutive patients who had undergon...

  9. Tumour necrosis is a postoperative prognostic marker for pancreatic cancer patients with a high interobserver reproducibility in histological evaluation

    Czech Academy of Sciences Publication Activity Database

    Hiraoka, N.; Ino, Y.; Sekine, S.; Tsuda, H.; Shimada, K.; Kosuge, T.; Závada, Jan; Yoshida, M.; Yamada, K.; Koyama, T.; Kanai, Y.

    2010-01-01

    Roč. 103, č. 7 (2010), s. 1057-1065. ISSN 0007-0920 Institutional research plan: CEZ:AV0Z40550506 Keywords : pancreatic cancer * hypoxia * prognostics Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.831, year: 2010

  10. Systematic assessment of prognostic gene signatures for breast cancer shows distinct influence of time and ER status

    International Nuclear Information System (INIS)

    The aim was to assess and compare prognostic power of nine breast cancer gene signatures (Intrinsic, PAM50, 70-gene, 76-gene, Genomic-Grade-Index, 21-gene-Recurrence-Score, EndoPredict, Wound-Response and Hypoxia) in relation to ER status and follow-up time. A gene expression dataset from 947 breast tumors was used to evaluate the signatures for prediction of Distant Metastasis Free Survival (DMFS). A total of 912 patients had available DMFS status. The recently published METABRIC cohort was used as an additional validation set. Survival predictions were fairly concordant across most signatures. Prognostic power declined with follow-up time. During the first 5 years of followup, all signatures except for Hypoxia were predictive for DMFS in ER-positive disease, and 76-gene, Hypoxia and Wound-Response were prognostic in ER-negative disease. After 5 years, the signatures had little prognostic power. Gene signatures provide significant prognostic information beyond tumor size, node status and histological grade. Generally, these signatures performed better for ER-positive disease, indicating that risk within each ER stratum is driven by distinct underlying biology. Most of the signatures were strong risk predictors for DMFS during the first 5 years of follow-up. Combining gene signatures with histological grade or tumor size, could improve the prognostic power, perhaps also of long-term survival

  11. Prognostic value of quantitative fluorodeoxyglucose measurements in newly diagnosed metastatic breast cancer

    International Nuclear Information System (INIS)

    The aim of this study was to determine the prognostic value of quantitative fluorodeoxyglucose (FDG) measurements (maximum standardized uptake value [SUVmax], metabolic tumor volume [MTV], and total lesion glycolysis [TLG]) in patients with newly diagnosed metastatic breast cancer (MBC). An IRB-approved retrospective review was performed of patients who underwent FDG positron emission tomography (PET)/computed tomography (CT) from 1/02 to 12/08 within 60 days of diagnosis MBC. Patients with FDG-avid lesions without receiving chemotherapy in the prior 30 days were included. Target lesions in bone, lymph node (LN), liver, and lung were analyzed for SUVmax, MTV, and TLG. Medical records were reviewed for patient characteristics and overall survival (OS). Cox regression was used to test associations between quantitative FDG measurements and OS. A total of 253 patients were identified with disease in bone (n = 150), LN (n = 162), liver (n = 48), and lung (n = 66) at the time of metastatic diagnosis. Higher SUVmax tertile was associated with worse OS in bone metastases (highest vs. lowest tertile hazard ratio [HR] = 3.1, P < 0.01), but not in LN, liver or lung (all P > 0.1). Higher MTV tertile was associated with worse OS in LN (HR = 2.4, P < 0.01) and liver (HR = 3.0, P = 0.02) metastases, but not in bone (P = 0.22) or lung (P = 0.14). Higher TLG tertile was associated with worse OS in bone (HR = 2.2, P = 0.02), LN (HR = 2.3, P < 0.01), and liver (HR = 4.9, P < 0.01) metastases, but not in lung (P = 0.19). We conclude measures of FDG avidity are prognostic biomarkers in newly diagnosed MBC. SUVmax and TLG were both predictors of survival in breast cancer patients with bone metastases. TLG may be a more informative biomarker of OS than SUVmax for patients with LN and liver metastases. Measures of fluorodeoxyglucose (FDG) avidity are prognostic biomarkers in newly diagnosed metastatic breast cancer. Volumetric measurements, such as total lesion glycolysis (TLG), may be

  12. The prognostic importance of miR-21 in stage II colon cancer: a population-based study

    DEFF Research Database (Denmark)

    Kjaer-Frifeldt, S.; Hansen, T. F.; Nielsen, B. S.;

    2012-01-01

    R-21), quantified by in situ hybridisation, in a unique, large population-based cohort. PATIENTS AND METHODS: The study included 764 patients diagnosed with stage II colon cancer in Denmark in the year 2003. One section from a representative paraffin-embedded tumour tissue specimen from each patient......BACKGROUND: Despite several years of research and attempts to develop prognostic models a considerable fraction of stage II colon cancer patients will experience relapse within few years from their operation. The aim of the present study was to investigate the prognostic importance of miRNA-21 (mi...... that increasing miR-21 expression levels were significantly correlated to decreasing RF-CSS. Further investigations of the clinical importance of miR-21 in the selection of high-risk stage II colon cancer patients are merited. British Journal of Cancer (2012) 107, 1169-1174. doi:10.1038/bjc.2012...

  13. Prognostic Impact of the 6th and 7th American Joint Committee on Cancer TNM Staging Systems on Esophageal Cancer Patients Treated With Chemoradiotherapy

    International Nuclear Information System (INIS)

    Purpose: The new 7th edition of the American Joint Committee on Cancer TNM staging system is based on pathologic data from esophageal cancers treated by surgery alone. There is no information available on evaluation of the new staging system with regard to prognosis of patients treated with chemoradiotherapy (CRT). The objective of this study was to evaluate the prognostic impact of the new staging system on esophageal cancer patients treated with CRT. Methods and Materials: A retrospective review was performed on 301 consecutive esophageal squamous cell carcinoma patients treated with CRT. Comparisons were made of the prognostic impacts of the 6th and 7th staging systems and the prognostic impacts of stage and prognostic groups, which were newly defined in the 7th edition. Results: There were significant differences between Stages I and III (p < 0.01) according to both editions. However, the 7th edition poorly distinguishes the prognoses of Stages III and IV (p = 0.36 by multivariate analysis) in comparison to the 6th edition (p = 0.08 by multivariate analysis), although these differences were not significant. For all patients, T, M, and gender were independent prognostic factors by multivariate analysis (p < 0.05). For the Stage I and II prognostic groups, survival curves showed a stepwise decrease with increase in stage, except for Stage IIA. However, there were no significant differences seen between each prognostic stage. Conclusions: Our study indicates there are several problems with the 7th TNM staging system regarding prognostic factors in patients undergoing CRT.

  14. Assessment of Diagnostic and Prognostic Role of Copeptin in the Clinical Setting of Sepsis

    Directory of Open Access Journals (Sweden)

    Stefania Battista

    2016-01-01

    Full Text Available The diagnostic and prognostic usefulness of copeptin were evaluated in septic patients, as compared to procalcitonin assessment. In this single centre and observational study 105 patients were enrolled: 24 with sepsis, 25 with severe sepsis, 15 with septic shock, and 41 controls, divided in two subgroups (15 patients with gastrointestinal bleeding and 26 with suspected SIRS secondary to trauma, acute coronary syndrome, and pulmonary embolism. Biomarkers were determined at the first medical evaluation and thereafter 24, 48, and 72 hours after admission. Definitive diagnosis and in-hospital survival rates at 30 days were obtained through analysis of medical records. At entry, copeptin proved to be able to distinguish cases from controls and also sepsis group from septic shock group, while procalcitonin could distinguish also severe sepsis from septic shock group. Areas under the ROC curve for copeptin and procalcitonin were 0.845 and 0.861, respectively. Noteworthy, patients with copeptin concentrations higher than the threshold value (23.2 pmol/L, calculated from the ROC curve, at admission presented higher 30-day mortality. No significant differences were found in copeptin temporal profile among different subgroups. Copeptin showed promising diagnostic and prognostic role in the management of sepsis, together with its possible role in monitoring the response to treatment.

  15. Assessment of Diagnostic and Prognostic Role of Copeptin in the Clinical Setting of Sepsis.

    Science.gov (United States)

    Battista, Stefania; Audisio, Umberto; Galluzzo, Claudia; Maggiorotto, Matteo; Masoero, Monica; Forno, Daniela; Pizzolato, Elisa; Ulla, Marco; Lucchiari, Manuela; Vitale, Annarita; Moiraghi, Corrado; Lupia, Enrico; Settanni, Fabio; Mengozzi, Giulio

    2016-01-01

    The diagnostic and prognostic usefulness of copeptin were evaluated in septic patients, as compared to procalcitonin assessment. In this single centre and observational study 105 patients were enrolled: 24 with sepsis, 25 with severe sepsis, 15 with septic shock, and 41 controls, divided in two subgroups (15 patients with gastrointestinal bleeding and 26 with suspected SIRS secondary to trauma, acute coronary syndrome, and pulmonary embolism). Biomarkers were determined at the first medical evaluation and thereafter 24, 48, and 72 hours after admission. Definitive diagnosis and in-hospital survival rates at 30 days were obtained through analysis of medical records. At entry, copeptin proved to be able to distinguish cases from controls and also sepsis group from septic shock group, while procalcitonin could distinguish also severe sepsis from septic shock group. Areas under the ROC curve for copeptin and procalcitonin were 0.845 and 0.861, respectively. Noteworthy, patients with copeptin concentrations higher than the threshold value (23.2 pmol/L), calculated from the ROC curve, at admission presented higher 30-day mortality. No significant differences were found in copeptin temporal profile among different subgroups. Copeptin showed promising diagnostic and prognostic role in the management of sepsis, together with its possible role in monitoring the response to treatment. PMID:27366743

  16. Clinical prognostic significance and pro-metastatic activity of RANK/RANKL via the AKT pathway in endometrial cancer.

    Science.gov (United States)

    Wang, Jing; Liu, Yao; Wang, Lihua; Sun, Xiao; Wang, Yudong

    2016-02-01

    RANK/RANKL plays a key role in metastasis of certain malignant tumors, which makes it a promising target for developing novel therapeutic strategies for cancer. However, the prognostic value and pro-metastatic activity of RANK in endometrial cancer (EC) remain to be determined. Thus, the present study investigated the effect of RANK on the prognosis of EC patients, as well as the pro-metastatic activity of EC cells. The results indicated that those with high expression of RANK showed decreased overall survival and progression-free survival. Statistical analysis revealed the positive correlations between RANK/RANKL expression and metastasis-related factors. Additionally, RANK/RANKL significantly promoted cell migration/invasion via activating AKT/β-catenin/Snail pathway in vitro. However, RANK/RANKL-induced AKT activation could be suppressed after osteoprotegerin (OPG) treatment. Furthermore, the combination of medroxyprogesterone acetate (MPA) and RANKL could in turn attenuate the effect of RANKL alone. Similarly, MPA could partially inhibit the RANK-induced metastasis in an orthotopic mouse model via suppressing AKT/β-catenin/Snail pathway. Therefore, therapeutic inhibition of MPA in RANK/RANKL-induced metastasis was mediated by AKT/β-catenin/Snail pathway both in vitro and in vivo, suggesting a potential target of RANK for gene-based therapy for EC. PMID:26734994

  17. Prognostic value of hemoglobin concentration in radiotherapy for cancer of supraglottic larynx

    International Nuclear Information System (INIS)

    Purpose: The aim of this work is the estimation of correlations between hemoglobin concentration either before or after radiotherapy and local tumor control probability for laryngeal cancer. Methods and Materials: Retrospective analysis of 847 cases of laryngeal supraglottic squamous cell carcinoma treated with radiation alone was performed using maximum likelihood estimations, and step-wise logistic regression. All patients were in good initial performance status (Karnofsky index >70). The minimum follow-up time was 3 years. Results: Logistic regression showed that the hemoglobin concentration after radiotherapy is an important prognostic factor. There was a very strong correlation between hemoglobin concentration and tumor local control probability. Hemoglobin concentration at the beginning of radiotherapy does not correlate with treatment outcome, but any decrease of hemoglobin during therapy is a strong prognostic factor for treatment failure. Conclusions: Although regression models with many variables may be instable, the present results suggest that hemoglobin concentration after treatment is at least as important as overall treatment time. It was not possible to find out whether the low concentration of hemoglobin is an independent cause of low TCP or whether it reflects other mechanisms that may influence both hemoglobin level and the TCP

  18. Prognostic significance of nuclear expression of UMP-CMP kinase in triple negative breast cancer patients

    Science.gov (United States)

    Liu, Ning Qing; De Marchi, Tommaso; Timmermans, Annemieke; Trapman-Jansen, Anita M. A. C.; Foekens, Renée; Look, Maxime P.; Smid, Marcel; van Deurzen, Carolien H. M.; Span, Paul N.; Sweep, Fred C. G. J.; Brask, Julie Benedicte; Timmermans-Wielenga, Vera; Foekens, John A.; Martens, John W. M.; Umar, Arzu

    2016-01-01

    We have previously identified UMP-CMP kinase (CMPK1) as a prognostic marker for triple negative breast cancer (TNBC) by mass spectrometry (MS). In this study we evaluated CMPK1 association to prognosis in an independent set of samples by immunohistochemistry (IHC) and assessed biological pathways associated to its expression through gene set enrichment analysis (GSEA). A total of 461 TNBC paraffin-embedded tissues were collected from different academic hospitals in Europe, incorporated into tissue micro-arrays (TMA), and stained for CMPK1 expression. We also collected gene expression data of 60 samples, which were also present in the TMA, for GSEA correlation analysis. CMPK1 IHC staining showed both cytoplasmic and nuclear components. While cytoplasmic CMPK1 did not show any association to metastasis free survival (MFS), nuclear CMPK1 was associated to poor prognosis independently from other prognostic factors in stratified Cox regression analyses. GSEA correlation analysis of the nuclear CMPK1-stratified gene expression dataset showed a significant enrichment of extracellular matrix (ECM; positive correlation) and cell cycle (negative correlation) associated genes. We have shown here that nuclear CMPK1 is indicative of poor prognosis in TNBCs and that its expression may be related to dysregulation of ECM and cell cycle molecules. PMID:27558661

  19. Metastatic spinal cord compression in non-small cell lung cancer patients. Prognostic factors in a series of 356 patients

    International Nuclear Information System (INIS)

    Patients with metastatic spinal cord compression (MSCC) from non-small cell lung cancer (NSCLC) have an unfavorable prognosis compared to most other MSCC patients. This study was performed to identify prognostic factors for functional outcome and survival in these patients after radiotherapy (RT) alone. Data of 356 patients irradiated for MSCC from NSCLC were retrospectively analyzed. Ten potential prognostic factors were investigated including age, gender, Eastern cooperative Oncology Group performance score (ECOG-PS), number of involved vertebrae, pre-RT ambulatory status, other bone metastases, visceral metastases, interval from cancer diagnosis to RT of MSCC, time developing motor deficits before RT, and the radiation schedule. On multivariate analysis, better functional outcome was associated with pre-RT ambulatory status (estimate: -0.84, p = 0.022), no visceral metastases (estimate: -1.15, p 15 months (estimate: +0.48, p = 0.019), and slower (> 7 days) development of motor deficits (estimate: +1.56, p 15 months (RR 0.84, p = 0.035), and slower (> 7 days) development of motor deficits (RR 0.78, p < 0.001). This study identified additional independent prognostic factors for outcomes after radiotherapy of MSCC from NSCLC. These prognostic factors can be used for stratification in future trials and can help develop prognostic scores for MSCC from NSCLC. (orig.)

  20. Epidermal growth factor receptor as a prognostic factor in locally advanced rectal-cancer patients treated with preoperative chemoradiation

    International Nuclear Information System (INIS)

    Purpose: We investigated the prognostic value of epidermal growth factor receptor (EGFR) expression in pretreatment biopsy specimens from patients with locally advanced rectal cancer treated with preoperative chemoradiation. Methods and Materials: Pretreatment biopsy specimens from 92 patients with locally advanced rectal cancer were examined for EGFR expression by immunohistochemistry. EGFR expression was assessed by immunoreactive score (IRS). The prognostic value of EGFR expression was evaluated according to the level of EGFR expression. Results: Epidermal growth factor receptor expression was positive in 65 patients (71%). EGFR expression levels were low (IRS 0 to 5) in 83 patients (90%) and high (IRS 6 to 7) in 9 patients (10%). A high level of EGFR expression was statistically significant for shorter overall survival (p = 0.013), disease-free survival (p = 0.002), and distant metastasis-free survival (p = 0.003), as compared with a low level of expression in univariate analysis. Grouping based on positive or negative EGFR expression did not represent prognostic significance for survival. In multivariate analysis, high EGFR expression was an independent prognostic factor for decreased disease-free survival (relative risk 2.4, p = 0.041) and distant metastasis-free survival (relative risk 2.6, p = 0.04). Conclusions: Our results suggest that high level of EGFR expression in a pretreatment biopsy specimen may be a significant adverse prognostic factor for disease-free survival and distant metastasis-free survival

  1. GP96 is over-expressed in oral cavity cancer and is a poor prognostic indicator for patients receiving radiotherapy

    International Nuclear Information System (INIS)

    Oral cavity cancers (ORC) are the most common cancers, and standard treatment is radical surgery with postoperative radiotherapy. However, locoregional failure remains a major problem, indicating radioresistance an important issue. Our previous work has shown that GP96 contributed to radioresistance in nasopharyngeal and oral cancer cell lines. In this study, we determined clinical significance of GP96 in ORC by evaluation of GP96 expression and its association with disease prognosis in patients receiving radiotherapy Total of 79 ORC patients (77 males, median age: 48 years old) receiving radical surgery and postoperative radiotherapy between Oct 1999 and Dec 2004 were enrolled. Patients in pathological stages II, III and IV were 16.5%, 16.5% and 67%, respectively. For each patient, a pair of carcinoma tissue and grossly adjacent normal mucosa was obtained. GP96-expression was examined by western blot analysis, and the association with clinicopathological status was determined. Three-year locoregional control (LRC), distant metastasis-free survival (DMFS), disease-specific survival (DSS) and overall survival (OS) rates were 69%, 79%, 63% and 57%, respectively. We found that 55 patients (70%) displayed GP96-overexpression in the tumor tissue, which correlated with a higher pN stage (p = 0.020) and tumor depth (> 10 mm) (p = 0.045). Nodal extracapsular spreading (ECS) and GP96-overexpression predicted adverse LRC (p = 0.049 and p = 0.008). When stratified by nodal ECS, the adverse impact of GP96 remained significant in three-year LRC (p = 0.004). In multivariate analysis, GP96-overexpression was also an independent predictor of LRC, DSS and OS (p = 0.018, p = 0.011 and p = 0.012). GP96 may play roles in radioresistance which attributes to tumor invasiveness in oral cancer patients receiving radiotherapy. GP96 may serve as a novel prognostic marker of radiotherapy. However, further independent studies are required to validate our findings in a larger series

  2. Prognostic Value of Immunohistochemical Staining of p53, bcl-2, and Ki-67 in Small Cell Lung Cancer

    OpenAIRE

    Paik, Kwang Hyun; Park, Yeon Hee; Ryoo, Baek-Yeol; Yang, Sung Hyun; Lee, Jae Cheol; Kim, Cheol Hyun; Ki, Seung Seog; Kim, Jung Min; Park, Myung Joon; Ahn, Heui June; Choi, Won; Chung, Jin Haeng

    2006-01-01

    Small cell lung cancer (SCLC) is one of the most fatal cancers in humans and many factors are known to be related to its poor prognosis. Immunohistochemical (IHC) stainings were done on SCLC specimens in order to investigate the prognostic value of the apoptosis-related gene expression and the tumor proliferative maker, and the relationships among these IHC results and patients clinical characteristics, chemoresponsiveness, and survival were analyzed. The medical records of 107 patients were ...

  3. Examination of thromboxane synthase as a prognostic factor and therapeutic target in non-small cell lung cancer.

    LENUS (Irish Health Repository)

    Cathcart, Mary-Clare

    2011-03-01

    Thromboxane synthase (TXS) metabolises prostaglandin H2 into thromboxanes, which are biologically active on cancer cells. TXS over-expression has been reported in a range of cancers, and associated with a poor prognosis. TXS inhibition induces cell death in-vitro, providing a rationale for therapeutic intervention. We aimed to determine the expression profile of TXS in NSCLC and if it is prognostic and\\/or a survival factor in the disease.

  4. AGR3 in Breast Cancer: Prognostic Impact and Suitable Serum-Based Biomarker for Early Cancer Detection

    Science.gov (United States)

    Garczyk, Stefan; von Stillfried, Saskia; Antonopoulos, Wiebke; Hartmann, Arndt; Schrauder, Michael G.; Fasching, Peter A.; Anzeneder, Tobias; Tannapfel, Andrea; Ergönenc, Yavuz; Knüchel, Ruth

    2015-01-01

    Blood-based early detection of breast cancer has recently gained novel momentum, as liquid biopsy diagnostics is a fast emerging field. In this study, we aimed to identify secreted proteins which are up-regulated both in tumour tissue and serum samples of breast cancer patients compared to normal tissue and sera. Based on two independent tissue cohorts (n = 75 and n = 229) and one serum cohort (n = 80) of human breast cancer and healthy serum samples, we characterised AGR3 as a novel potential biomarker both for breast cancer prognosis and early breast cancer detection from blood. AGR3 expression in breast tumours is significantly associated with oestrogen receptor α (P<0.001) and lower tumour grade (P<0.01). Interestingly, AGR3 protein expression correlates with unfavourable outcome in low (G1) and intermediate (G2) grade breast tumours (multivariate hazard ratio: 2.186, 95% CI: 1.008-4.740, P<0.05) indicating an independent prognostic impact. In sera analysed by ELISA technique, AGR3 protein concentration was significantly (P<0.001) elevated in samples from breast cancer patients (n = 40, mainly low stage tumours) compared to healthy controls (n = 40). To develop a suitable biomarker panel for early breast cancer detection, we measured AGR2 protein in human serum samples in parallel. The combined AGR3/AGR2 biomarker panel achieved a sensitivity of 64.5% and a specificity of 89.5% as shown by receiver operating characteristic (ROC) curve statistics. Thus our data clearly show the potential usability of AGR3 and AGR2 as biomarkers for blood-based early detection of human breast cancer. PMID:25875093

  5. Enhancer of zeste homolog 2 as an independent prognostic marker for cancer: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Shuling Chen

    Full Text Available Novel biomarkers are of particular interest for predicting cancer prognosis. This study aimed to explore the associations between enhancer of zeste homolog 2 (EZH2 and patient survival in various cancers.Relevant literature was retrieved from PubMed and Web of Science databases. Pooled hazard ratios (HRs, odds ratios (ORs, and 95% confidence intervals (CIs were calculated.Forty-nine studies (8,050 patients were included. High EZH2 expression was significantly associated with shorter overall (hazard ratio [HR] 1.74, 95% CI: 1.46-2.07, disease-free (HR 1.59, 95% CI: 1.27-1.99, metastasis-free (HR 2.19, 95% CI: 1.38-3.47, progression-free (HR 2.53, 95% CI: 1.52-4.21, cancer-specific (HR 3.13, 95% CI: 1.70-5.74, and disease-specific (HR 2.29, 95% CI: 1.56-3.35 survival, but not recurrence-free survival (HR 1.38, 95% CI: 0.93-2.06. Moreover, EZH2 expression significantly correlated with distant metastasis (OR 3.25, 95% CI: 1.07-9.87 in esophageal carcinoma; differentiation (OR 3.00, 95% CI: 1.37-6.55 in non-small cell lung cancer; TNM stage (OR 3.18, 95% CI: 2.49-4.08 in renal cell carcinoma; and histological grade (OR 4.50, 95% CI: 3.33-6.09, estrogen receptor status (OR 0.15, 95% CI: 0.11-0.20 and progesterone receptor status (OR 0.30, 95% CI: 0.23-0.39 in breast cancer.Our results suggested that EZH2 might be an independent prognostic factor for multiple survival measures in different cancers.

  6. Expression of FXYD-3 is an Independent Prognostic Factor in Rectal Cancer Patients With Preoperative Radiotherapy

    International Nuclear Information System (INIS)

    Purpose: FXYD-3 (MAT-8) is overexpressed in several types of cancers; however, its clinical relevance in rectal cancers has not been studied. Therefore, we examined FXYD-3 expression in rectal cancers from the patients who participated in a Swedish clinical trial of preoperative radiotherapy (RT) to determine whether FXYD-3 was overexpressed in rectal cancers and correlated with RT, survival, and other clinicopathologic variables. Methods and Materials: The study included 140 rectal cancer patients who participated in a clinical trial of preoperative RT, 65 with and 75 without RT before surgery. FXYD-3 expression was immunohistochemically examined in distant (n = 70) and adjacent (n = 101) normal mucosa, primary tumors (n = 140), and lymph node metastasis (n = 36). Results: In the whole cohort, strong FXYD-3 expression was correlated with infiltrative tumor growth (p = 0.02). In the RT group, strong FXYD-3 expression alone (p = 0 .02) or combined with phosphatase of regenerating liver was associated with an unfavorable prognosis (p = 0.02), independent of both TNM stage and tumor differentiation. In tumors with strong FXYD-3 expression, there was less tumor necrosis (p = 0.02) and a trend toward increased incidence of distant metastasis (p = 0.08) after RT. None of these effects was seen in the non-RT group. FXYD-3 expression in the primary tumors tended to be increased compared with normal mucosa regardless of RT. Conclusion: FXYD-3 expression was a prognostic factor independent of tumor stage and differentiation in patients receiving preoperative RT for rectal cancer.

  7. Pathological complete response in breast cancer patients following neoadjuvant chemotherapy at a Comprehensive Cancer Center: The natural history of an elusive prognosticator

    OpenAIRE

    Fayanju, Oluwadamilola M.; NWAOGU, IHEOMA; Jeffe, Donna B.; Margenthaler, Julie A

    2015-01-01

    Given the prognostic significance of pathological complete response (pCR) to neoadjuvant chemotherapy, we sought to chronicle the clinical course of breast cancer patients whose tumors exhibited pCR at our institution. We retrospectively reviewed 5,533 cancer center patients treated for a first primary breast cancer between March, 1999 and September, 2010 to identify those who received neoadjuvant chemotherapy that resulted in pCR (i.e., no residual invasive malignancy in the breast or axilla...

  8. Prognostic factors of tumor recurrence in completely resected non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Tantraworasin A

    2013-06-01

    Full Text Available Apichat Tantraworasin,1 Somcharean Seateang,1 Nirush Lertprasertsuke,2 Nuttapon Arreyakajohn,3 Choosak Kasemsarn,4 Jayanton Patumanond5 1General Thoracic Unit, Department of Surgery, Faculty of Medicine, Chiang Mai University Hospital, Chiang Mai, Thailand; 2Department of Pathology, Faculty of Medicine, Chiang Mai University Hospital, Chiang Mai, Thailand; 3Cardiovascular Thoracic Unit, Department of Surgery, Lampang Hospital, Lampang, Thailand; 4Cardiovascular Thoracic Unit, Department of Surgery, Chest Institute, Nonthaburi, Thailand; 5Department of Community Medicine, Faculty of Medicine, Chiang Mai University Hospital, Chiang Mai, Thailand Background: Patients with completely resected non-small cell lung cancer (NSCLC have an excellent outcome; however tumor recurs in 30%-77% of patients. This study retrospectively analyzed the clinicopathologic features of patients with any operable stage of NSCLC to identify the prognostic factors that influence tumor recurrence, including intratumoral blood vessel invasion (IVI, tumor size, tumor necrosis, and nodal involvement. Methods: From January 2002 to December 2011, 227 consecutive patients were enrolled in this study. They were divided into two groups: the “no recurrence” group and the “recurrence” group. Recurrence-free survival was analyzed by multivariable Cox regression analysis, stratified by tumor staging, chemotherapy, and lymphatic invasion. Results: IVI, tumor necrosis, tumor diameter more than 5 cm, and nodal involvement were identified as independent prognostic factors of tumor recurrence. The hazard ratio (HR of patients with IVI was 2.1 times higher than that of patients without IVI (95% confident interval [CI]: 1.4–3.2 (P = 0.001.The HR of patients with tumor necrosis was 2.1 times higher than that of patients without tumor necrosis (95% CI: 1.3–3.4 (P = 0.001. Patients who had a maximum tumor diameter greater than 5 cm had significantly higher risk of recurrence than

  9. Prognostic role of HOTAIR in four estrogen-dependent malignant tumors: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Li J

    2015-06-01

    Full Text Available Jing Li,1 Wen Wen,2 Shu Zhao,1 Jingxuan Wang,1 Jingyu Chen,1 Yanrong Wang,3 Qingyuan Zhang11Department of Internal Medicine, 2Department of Anesthesia, The Third Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People’s Republic of China; 3Key Laboratory of Fertility Maintenance, Ministry of Education, Ningxia Medical University, Xingqing, Yinchuan, Ningxia, People’s Republic of ChinaBackground: HOX transcript antisense intergenic RNA (HOTAIR, a long non-coding RNA transcribed from the antisense strand of the HOXC gene locus, has been shown to be overexpressed in various carcinomas and is thought to be an indicator of poor prognosis. Recently, HOTAIR was found to be an estrogen-responsive gene. We therefore conducted a meta-analysis to systematically summarize and clarify the association between HOTAIR expression and prognosis in the four main estrogen-dependent tumors.Methods: A systematic search of studies that examined the association and prognostic impact of HOTAIR in four of the main estrogen-dependent tumors was conducted in PubMed and Embase. Hazard ratios (HRs and 95% confidence intervals (95% CIs were calculated to pool the effect size.Results: A total of 1,200 patients from eight eligible studies were included. The current study found an association between HOTAIR expression and overall survival (OS in four estrogen-dependent tumor types (HR, 1.99; 95% CI: 1.02–3.90; PHeterogeneity=0.001. Subgroup analyses indicated that high HOTAIR expression appeared to be a potential prognostic biomarker in non-breast cancer patients (HR, 2.72; 95% CI: 1.65–4.48. There was also an increased risk in Asian populations (HR, 2.55; 95% CI: 1.62–4.00 compared with Caucasian populations (HR, 1.19; 95% CI: 0.16–8.83 and in patients without preoperative treatment (HR, 2.55; 95% CI: 1.62–4.00 compared with patients with preoperative treatment (HR, 1.19; 95% CI: 0.16–8.83. In addition, the HRs of patients with

  10. Improving Clinical Risk Stratification at Diagnosis in Primary Prostate Cancer: A Prognostic Modelling Study

    Science.gov (United States)

    Wright, Karen A.; Muir, Kenneth R.; Gavin, Anna

    2016-01-01

    Introduction Over 80% of the nearly 1 million men diagnosed with prostate cancer annually worldwide present with localised or locally advanced non-metastatic disease. Risk stratification is the cornerstone for clinical decision making and treatment selection for these men. The most widely applied stratification systems use presenting prostate-specific antigen (PSA) concentration, biopsy Gleason grade, and clinical stage to classify patients as low, intermediate, or high risk. There is, however, significant heterogeneity in outcomes within these standard groupings. The International Society of Urological Pathology (ISUP) has recently adopted a prognosis-based pathological classification that has yet to be included within a risk stratification system. Here we developed and tested a new stratification system based on the number of individual risk factors and incorporating the new ISUP prognostic score. Methods and Findings Diagnostic clinicopathological data from 10,139 men with non-metastatic prostate cancer were available for this study from the Public Health England National Cancer Registration Service Eastern Office. This cohort was divided into a training set (n = 6,026; 1,557 total deaths, with 462 from prostate cancer) and a testing set (n = 4,113; 1,053 total deaths, with 327 from prostate cancer). The median follow-up was 6.9 y, and the primary outcome measure was prostate-cancer-specific mortality (PCSM). An external validation cohort (n = 1,706) was also used. Patients were first categorised as low, intermediate, or high risk using the current three-stratum stratification system endorsed by the National Institute for Health and Care Excellence (NICE) guidelines. The variables used to define the groups (PSA concentration, Gleason grading, and clinical stage) were then used to sub-stratify within each risk category by testing the individual and then combined number of risk factors. In addition, we incorporated the new ISUP prognostic score as a discriminator

  11. Standardized FDG uptake as a prognostic variable and as a predictor of incomplete cytoreduction in primary advanced ovarian cancer

    International Nuclear Information System (INIS)

    Introduction. In patients with advanced ovarian cancer undergoing preoperative PET/CT, we investigated the prognostic value of SUV in the primary tumor and we evaluated the value of SUV for predicting incomplete primary cytoreduction (macroscopic residual tumor). Material and methods. From September 2004 to August 2007, 201 consecutive patients with a pelvic tumor and a Risk of Malignancy Index (RMI) > 150 based on serum CA-125, ultrasound examinations and menopausal state, underwent PET/CT within two weeks prior to standard surgery/debulking of a pelvic tumor. At two-year follow-up (August 15, 2009) the association between SUV and overall survival/cytoreductive result were analyzed in 60 ovarian cancer patients (58 stage III and two stage IV). Results. At inclusion median age was 62 years (range 35-85 years); 97% (58/60) had a performance status ≤2; 42% (25/60) underwent complete debulking (no macroscopic residual tumor); median SUVmax was 13.5 (range 2.5-39.0). Median follow-up was 30.2 months. At follow-up 57% (34/60) were alive and 43% (26/60) had died from ovarian cancer. SUVmax in patients alive was not statistically different from SUVmax in dead patients (p=0.69), and SUVmax was not correlated with the amount of residual tumor after surgery (p=0.19). Using univariate Cox regression analysis, residual tumor was a significant prognostic variable (p=0.001); SUVmax was not a statistically significant prognostic variable (p=0.86). Discussion. FDG uptake (SUVmax) in the primary tumor of patients with advanced ovarian cancer was not a prognostic variable and the FDG uptake did not predict complete cytoreduction after primary surgery. Future prospective clinical trials will need to clarify if other PET tracers can serve as prognostic variables in ovarian cancer

  12. Surgery and radiotherapy of brain metastases in breast cancer patients - an analysis of survival and prognostic factors

    International Nuclear Information System (INIS)

    The study assesses the results of radical neurosurgical treatment and adjuvant radiotherapy of one or two brain metastases in breast cancer patients. The survival analyses were performed according to different factors and in different prognostic class. We analyzed 31 breast cancer patients with one or two metastatic brain tumours treated at Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology (MSMCC) between the years 1998 and 2005. The patients underwent neurosurgical excision with radical intent, followed by whole brain irradiation. Overall survival from the time of the diagnosis of brain metastases has been assessed both in the entire group and in the different prognostic groups. Median survival calculated for the entire group was 12 months (range: 2-77 months) while in the different prognostic groups it reached: 28 months (range: 2-77 months) for class I patients, 14 months (range: 5-17 months) for class II patients and 3 months (range: 3-8 months) for class III patients. We had observed that prognosis was significantly better in patients with a good performance status, with a single brain metastases and without the symptoms of active extracranial disease. The time lapse from the diagnosis of breast cancer to the development of brain metastases, the localization of the metastatic mass in the brain and systematic treatment did not affect survival. The overall survival of breast cancer patients with brain metastases treated neurosurgically with adjuvant whole brain radiotherapy is significantly longer in case of prognostic class I patients, as compared to prognostic class II and III patients. The patients to benefit the most from surgery and irradiation were in good overall condition, without symptoms of active extracranial disease and with a single metastatic brain tumour. In the case of such patients combined therapy (surgery and whole brain, radiotherapy) should always be considered, as radiotherapy alone may not allow to achieve comparable

  13. β-catenin-independent WNT signaling and Ki67 in contrast to the estrogen receptor status are prognostic and associated with poor prognosis in breast cancer liver metastases

    OpenAIRE

    Bleckmann, Annalen; Conradi, Lena-Christin; Menck, Kerstin; Schmick, Nadine Annette; Schubert, Antonia; Rietkötter, Eva; Arackal, Jetcy; Middel, Peter; Schambony, Alexandra; Liersch, Torsten; Homayounfar, Kia; Beißbarth, Tim; Klemm, Florian; Binder, Claudia; Pukrop, Tobias

    2016-01-01

    Liver metastasis development in breast cancer patients is common and confers a poor prognosis. So far, the prognostic significance of surgical resection and clinical relevance of biomarker analysis in metastatic tissue have barely been investigated. We previously demonstrated an impact of WNT signaling in breast cancer brain metastasis. This study aimed to investigate the value of established prognostic markers and WNT signaling components in liver metastases. Overall N = 34 breast cancer liv...

  14. Germline DNA copy number aberrations identified as potential prognostic factors for breast cancer recurrence.

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    Yadav Sapkota

    Full Text Available Breast cancer recurrence (BCR is a common treatment outcome despite curative-intent primary treatment of non-metastatic breast cancer. Currently used prognostic and predictive factors utilize tumor-based markers, and are not optimal determinants of risk of BCR. Germline-based copy number aberrations (CNAs have not been evaluated as determinants of predisposition to experience BCR. In this study, we accessed germline DNA from 369 female breast cancer subjects who received curative-intent primary treatment following diagnosis. Of these, 155 experienced BCR and 214 did not, after a median duration of follow up after breast cancer diagnosis of 6.35 years (range = 0.60-21.78 and 8.60 years (range = 3.08-13.57, respectively. Whole genome CNA genotyping was performed on the Affymetrix SNP array 6.0 platform. CNAs were identified using the SNP-Fast Adaptive States Segmentation Technique 2 algorithm implemented in Nexus Copy Number 6.0. Six samples were removed due to poor quality scores, leaving 363 samples for further analysis. We identified 18,561 CNAs with ≥1 kb as a predefined cut-off for observed aberrations. Univariate survival analyses (log-rank tests identified seven CNAs (two copy number gains and five copy neutral-loss of heterozygosities, CN-LOHs showing significant differences (P<2.01×10(-5 in recurrence-free survival (RFS probabilities with and without CNAs.We also observed three additional but distinct CN-LOHs showing significant differences in RFS probabilities (P<2.86×10(-5 when analyses were restricted to stratified cases (luminal A, n = 208 only. After adjusting for tumor stage and grade in multivariate analyses (Cox proportional hazards models, all the CNAs remained strongly associated with the phenotype of BCR. Of these, we confirmed three CNAs at 17q11.2, 11q13.1 and 6q24.1 in representative samples using independent genotyping platforms. Our results suggest further investigations on the potential use of germline DNA

  15. miR-422a is an independent prognostic factor and functions as a potential tumor suppressor in colorectal cancer

    Science.gov (United States)

    Zheng, Gui-Xi; Qu, Ai-Lin; Yang, Yong-Mei; Zhang, Xin; Zhang, Shou-Cai; Wang, Chuan-Xin

    2016-01-01

    AIM: To determine the expression of miR-422a in colorectal cancer (CRC) tissues and to further explore the prognostic value and function of miR-422a in CRC carcinogenesis. METHODS: miR-422a expression was analyzed in 102 CRC tissues and paired normal mucosa adjacent to carcinoma by quantitative real-time PCR. The relationship of miR-422a expression with clinicopathological parameters was also analyzed. Kaplan-Meier analysis and Cox multivariate analysis were performed to estimate the potential role of miR-422a. Cell proliferation, migration, and invasion were used for in vitro functional analysis of miR-422a. RESULTS: The levels of miR-422a were dramatically reduced in CRC tissues compared with normal mucosa (P < 0.05), and significantly correlated with local invasion (P = 0.004) and lymph node metastasis (P < 0.001). Kaplan-Meier survival and Cox regression multivariate analyses revealed that miR-422a expression (HR = 0.568, P = 0.015) and clinical TNM stage (HR = 2.942, P = 0.003) were independent prognostic factors for overall survival in CRC patients. Furthermore, in vitro experiments showed that overexpression of miR-422a inhibited the proliferation, migration, and invasion of SW480 and HT-29 cells. CONCLUSION: Down-regulation of miR-422a may serve as an independent prognosis factor in CRC. MiR-422a functions as a tumor suppressor and regulates progression of CRC. PMID:27350737

  16. Correlation between 18F-FDG uptake on PET/CT and prognostic factors in triple-negative breast cancer

    International Nuclear Information System (INIS)

    The purpose of this study was to investigate whether a correlation exists between 18F-fluorodeoxyglucose (FDG) uptake and prognostic factors in triple-negative breast cancer (TNBC). Between January 2009 and December 2013, 103 patients (mean age, 50.6 years) with primary TNBC (mean, 2.6 cm; range, 1.0-6.5 cm) underwent 18F-FDG PET/CT for initial staging. Correlations between maximum standardized uptake value (SUVmax) on PET/CT and prognostic factors including tumour size, nodal status, histological grade, Ki-67 proliferation index, tumour suppressor p53, and 'basal-like' markers (epidermal growth factor receptor and CK 5/6) were assessed. The mean SUVmax of the 103 tumours was 10.94 ± 5.25 (range: 2-32.8). There was a positive correlation between SUVmax and Ki-67 (Spearman's rho = 0.29, P = 0.003) and tumour size (Spearman's rho = 0.27, P = 0.006), whereas this relationship was not observed in the nodal status, histological grade, p53 status and 'basal-like' phenotypes. In a multivariate regression analysis, Ki-67 (P < 0.001) and tumour size (P = 0.009) were significantly associated with SUVmax in TNBCs. Increased 18F-FDG uptake on PET/CT was correlated with a high Ki-67 proliferation index and larger tumour size in TNBC. These results suggest a potential role of 18F-FDG PET/CT in identifying TNBC with more aggressive behaviour. (orig.)

  17. Prospective assessment of the prognostic value of circulating tumor cells and their clusters in patients with advanced-stage breast cancer.

    Science.gov (United States)

    Mu, Zhaomei; Wang, Chun; Ye, Zhong; Austin, Laura; Civan, Jesse; Hyslop, Terry; Palazzo, Juan P; Jaslow, Rebecca; Li, Bingshan; Myers, Ronald E; Jiang, Juntao; Xing, Jinliang; Yang, Hushan; Cristofanilli, Massimo

    2015-12-01

    The enumeration of circulating tumor cells (CTCs) provides important prognostic values in patients with metastatic breast cancer. Recent studies indicate that individual CTCs form clusters and these CTC-clusters play an important role in tumor metastasis. We aimed to assess whether quantification of CTC-clusters provides additional prognostic value over quantification of individual CTCs alone. In 115 prospectively enrolled advanced-stage (III and IV) breast cancer patients, CTCs and CTC-clusters were counted in 7.5 ml whole blood using the CellSearch system at baseline before first-line therapy. The individual and joint effects of CTC and CTC cluster counts on patients' progression-free survival (PFS) were analyzed using Cox proportional hazards modeling. Of the 115 patients, 36 (31.3 %) had elevated baseline CTCs (≥5 CTCs/7.5 ml) and 20 (17.4 %) had CTC-clusters (≥2 CTCs/7.5 ml). Patients with elevated CTCs and CTC-clusters both had worse PFS with a hazard ratio (HR) of 2.76 [95 % confidence interval (CI) 1.57-4.86, P log-rank = 0.0005] and 2.83 (1.48-5.39, P log-rank = 0.001), respectively. In joint analysis, compared with patients with IBC), the most aggressive form of breast cancer with the poorest survival. Baseline counts of both individual CTCs and CTC-clusters were associated with PFS in advanced-stage breast cancer patients. CTC-clusters might provide additional prognostic value compared with CTC enumeration alone, in patients with elevated CTCs. PMID:26573830

  18. A comparison of the prognostic value of preoperative inflammation-based scores and TNM stage in patients with gastric cancer

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    Pan QX

    2015-06-01

    Full Text Available Qun-Xiong Pan,* Zi-Jian Su,* Jian-Hua Zhang, Chong-Ren Wang, Shao-Ying KeDepartment of Oncosurgery, Quanzhou First Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, People’s Republic of China*These authors contributed equally to this workBackground: People’s Republic of China is one of the countries with the highest incidence of gastric cancer, accounting for 45% of all new gastric cancer cases in the world. Therefore, strong prognostic markers are critical for the diagnosis and survival of Chinese patients suffering from gastric cancer. Recent studies have begun to unravel the mechanisms linking the host inflammatory response to tumor growth, invasion and metastasis in gastric cancers. Based on this relationship between inflammation and cancer progression, several inflammation-based scores have been demonstrated to have prognostic value in many types of malignant solid tumors.Objective: To compare the prognostic value of inflammation-based prognostic scores and tumor node metastasis (TNM stage in patients undergoing gastric cancer resection.Methods: The inflammation-based prognostic scores were calculated for 207 patients with gastric cancer who underwent surgery. Glasgow prognostic score (GPS, neutrophil lymphocyte ratio (NLR, platelet lymphocyte ratio (PLR, prognostic nutritional index (PNI, and prognostic index (PI were analyzed. Linear trend chi-square test, likelihood ratio chi-square test, and receiver operating characteristic were performed to compare the prognostic value of the selected scores and TNM stage.Results: In univariate analysis, preoperative serum C-reactive protein (P<0.001, serum albumin (P<0.001, GPS (P<0.001, PLR (P=0.002, NLR (P<0.001, PI (P<0.001, PNI (P<0.001, and TNM stage (P<0.001 were significantly associated with both overall survival and disease-free survival of patients with gastric cancer. In multivariate analysis, GPS (P=0.024, NLR (P=0.012, PI (P=0.001, TNM stage (P<0.001, and degree of

  19. A Prognostic Index for Predicting Lymph Node Metastasis in Minor Salivary Gland Cancer

    International Nuclear Information System (INIS)

    Purpose: Large studies examining the clinical and pathological factors associated with nodal metastasis in minor salivary gland cancer are lacking in the literature. Methods and Materials: Using the Surveillance, Epidemiology, and End Results (SEER) database, we identified 2,667 minor salivary gland cancers with known lymph node status from 1988 to 2004. Univariate and multivariate analyses were conducted to identify factors associated with the use of neck dissection, the use of external beam radiation therapy, and the presence of cervical lymph node metastases. Results: Four hundred twenty-six (16.0%) patients had neck nodal involvement. Factors associated with neck nodal involvement on univariate analysis included increasing age, male sex, increasing tumor size, high tumor grade, T3-T4 stage, adenocarcinoma or mucoepidermoid carcinomas, and pharyngeal site of primary malignancy. On multivariate analysis, four statistically significant factors were identified, including male sex, T3-T4 stage, pharyngeal site of primary malignancy, and high-grade adenocarcinoma or high-grade mucoepidermoid carcinomas. The proportions (and 95% confidence intervals) of patients with lymph node involvement for those with 0, 1, 2, 3, and 4 of these prognostic factors were 0.02 (0.01-0.03), 0.09 (0.07-0.11), 0.17 (0.14-0.21), 0.41 (0.33-0.49), and 0.70 (0.54-0.85), respectively. Grade was a significant predictor of metastasis for adenocarcinoma and mucoepidermoid carcinoma but not for adenoid cystic carcinoma. Conclusions: A prognostic index using the four clinicopathological factors listed here can effectively differentiate patients into risk groups of nodal metastasis. The precision of this index is subject to the limitations of SEER data and should be validated in further clinical studies.

  20. Expression and prognostic significance of cancer-testis antigens (CTA in intrahepatic cholagiocarcinoma

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    Chen Sun-xiao

    2011-01-01

    Full Text Available Abstract Background Cancer-testis antigens (CTAs are suitable targets for cancer-specific immunotherapy. The aim of the study is to investigate the expression of CTAs in intrahepatic cholagiocarcinoma (IHCC and evaluate their potential therapeutic values. Methods Eighty-nine IHCC patients were retrospectively assessed for their expression of CTAs and HLA Class I by immunohistochemistry using the following antibodies: MA454 recognizing MAGE-A1, 57B recognizing multiple MAGE-A (MAGE-A3/A4, E978 recognizing NY-ESO-1, and EMR8-5 recognizing HLA class I. The clinicopathological and prognostic significance of individual CTA markers and their combination were further evaluated. Results The expression rates of MAGE-A1, MAGE-A3/4 and NY-ESO-1 were 29.2%, 27.0% and 22.5%, respectively. The concomitant expression of CTAs and HLA class I antigen was observed in 33.7% of the IHCC tumors. We found that positive MAGE-3/4 expression correlated with larger tumor size (≥ 5 cm, tumor recurrence and poor prognosis. Moreover, we identified 52 cases (58.4% of IHCC patients with at least one CTA marker expression, and this subgroup displayed a higher frequency of larger tumor size and a shorter survival than the other cases. Furthermore, expression of at least one CTA marker was also an independent prognostic factor in patients with IHCC. Conclusion Our data suggest that specific immunotherapy targeted CTAs might be a novel treatment option for IHCC patients.

  1. Identifying common prognostic factors in genomic cancer studies: A novel index for censored outcomes

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    Moreau Thierry

    2010-03-01

    Full Text Available Abstract Background With the growing number of public repositories for high-throughput genomic data, it is of great interest to combine the results produced by independent research groups. Such a combination allows the identification of common genomic factors across multiple cancer types and provides new insights into the disease process. In the framework of the proportional hazards model, classical procedures, which consist of ranking genes according to the estimated hazard ratio or the p-value obtained from a test statistic of no association between survival and gene expression level, are not suitable for gene selection across multiple genomic datasets with different sample sizes. We propose a novel index for identifying genes with a common effect across heterogeneous genomic studies designed to remain stable whatever the sample size and which has a straightforward interpretation in terms of the percentage of separability between patients according to their survival times and gene expression measurements. Results The simulations results show that the proposed index is not substantially affected by the sample size of the study and the censoring. They also show that its separability performance is higher than indices of predictive accuracy relying on the likelihood function. A simulated example illustrates the good operating characteristics of our index. In addition, we demonstrate that it is linked to the score statistic and possesses a biologically relevant interpretation. The practical use of the index is illustrated for identifying genes with common effects across eight independent genomic cancer studies of different sample sizes. The meta-selection allows the identification of four genes (ESPL1, KIF4A, HJURP, LRIG1 that are biologically relevant to the carcinogenesis process and have a prognostic impact on survival outcome across various solid tumors. Conclusion The proposed index is a promising tool for identifying factors having a

  2. Evaluation of the prognostic benefit of identifying the probable primary site in cancer of unknown primary

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    Das Joyutpal

    2015-09-01

    Full Text Available With the development of site-specific cancer therapy, identifying the primary origin allows the oncologist to personalise therapy for patients with the cancer of unknown primaries (CUPs. At present, immunohistochemistry (IHC screening is the standard method used to postulate the primary site in CUP. In this retrospective study, we evaluated the prognostic benefit of identifying the primary site in CUP. All 84 patients who presented with suspected CUP to the Royal Stoke University Hospital between 2011 and 2012 were included in our study. Forty-eight percent (40/84 of these patients were unable to undergo necessary investigations to identify primary sites because of poor performance status. IHC screening was able to postulate the primary site in 59% (26/44 of the remaining patients with confirmed CUP. Therefore, the primary site was not identified in a significant proportion of patients with CUP. The median survival of confirmed CUP with probable primary site was 2.0 months (95% confidence interval (CI: 1.2 to 2.9 months, whereas the median survival of confirmed CUP with no probable primary site was 4.1 months (95% CI: 1.5 to 9.7 months. This difference in survival time was statistically significant. In addition, using the Cox regression model, we found that patients with confirmed CUP with primary sites had prognostically unfavourable diseases with a shorter median survival, regardless of the age of disease onset, gender, sites of metastases or number of metastases. One approach to improve the survival would be to start systemic therapy at the earliest possible opportunity rather than waiting for all investigation results, such as IHC.

  3. Functional analysis of prognostic gene expression network genes in metastatic breast cancer models.

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    Thomas R Geiger

    Full Text Available Identification of conserved co-expression networks is a useful tool for clustering groups of genes enriched for common molecular or cellular functions [1]. The relative importance of genes within networks can frequently be inferred by the degree of connectivity, with those displaying high connectivity being significantly more likely to be associated with specific molecular functions [2]. Previously we utilized cross-species network analysis to identify two network modules that were significantly associated with distant metastasis free survival in breast cancer. Here, we validate one of the highly connected genes as a metastasis associated gene. Tpx2, the most highly connected gene within a proliferation network specifically prognostic for estrogen receptor positive (ER+ breast cancers, enhances metastatic disease, but in a tumor autonomous, proliferation-independent manner. Histologic analysis suggests instead that variation of TPX2 levels within disseminated tumor cells may influence the transition between dormant to actively proliferating cells in the secondary site. These results support the co-expression network approach for identification of new metastasis-associated genes to provide new information regarding the etiology of breast cancer progression and metastatic disease.

  4. Prognostic significance of new onset ascites in patients with pancreatic cancer

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    Luzardo German

    2006-03-01

    Full Text Available Abstract Background The purpose of this study was to determine risk factors for development of malignant ascites and its prognostic significance in patients with pancreatic cancer. Methods A prospective database was queried to identify patients with pancreatic cancer who develop ascites. Stage at presentation, size, and location of primary tumor, treatment received and length of survival after onset of ascites were determined. Results A total of 15 patients were identified. Of which 4 patients (1 stage II, 3 stage III underwent pancreaticoduodenectomy and manifested with ascites 2, 3, 24 and 47 months after surgery (tumor size 2.9 ± 1.32 cm. All but one of the remaining 11 patients (tumor size 4.4 ± 3.38 cm presented with metastatic disease, and all developed malignant ascites 9 months after diagnosis, dying 2 months later. Resected patients lived longer before the onset of ascites, but not after. Conclusion Once diagnosed, ascites in pancreatic cancer patients heralds imminent death. Limited survival should be considered when determining the aggressiveness of further intervention.

  5. The prognostic value of the nodal ratio in N1 breast cancer

    International Nuclear Information System (INIS)

    Although the nodal ratio (NR) has been recognized as a prognostic factor in breast cancer, its clinical implication in patients with 1-3 positive nodes (N1) remains unclear. Here, we evaluated the prognostic value of the NR and identified other clinico-pathologic variables associated with poor prognosis in these patients. We analyzed 130 patients with N1 invasive breast cancer who were treated at Seoul National University Bundang Hospital from March 2003 to December 2007. Disease-free survival (DFS), locoregional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) were compared according to the NR with a cut-off value of 0.15. We followed patients' recovery for a median duration of 59 months. An NR > 0.15 was found in 23.1% of patients, and a median of 18 nodes were dissected per patient (range 1-59). The NR was statistically independent from other prognostic variables, such as patient age, T stage, extent of surgery, pathologic factors in the chi square test. On univariate analysis, patients with a NR > 0.15 had significantly lower 5-year LRRFS (88.7% vs. 97.9%, p = 0.033) and 5-year DMFS (81.3% vs. 96.4%, p = 0.029) and marginally lower 5-year DFS (81.3% vs. 94.0%, p = 0.069) than those with a NR ≤0.15, respectively. Since the predictive power of the NR was found to differ with diverse clinical and pathologic variables, we performed adjusted analysis stratified by age, pathologic characteristics, and adjuvant treatments. Only young patients with a NR > 0.15 showed significantly lower DFS (p = 0.027) as well as those presenting an unfavorable pathologic profile such as advanced T stage (p = 0.034), histologic grade 3 (p = 0.034), positive lymphovascular invasion (p = 0.037), involved resection margin (p = 0.007), and no chemotherapy (p = 0.014) or regional radiotherapy treatment (p = 0.039). On multivariate analysis, a NR > 0.15 was significantly associated with lower DFS (p = 0.043) and DMFS (p = 0.012), but not LRRFS (p = 0

  6. Prognostic factors and patterns of failure in pathologic stage II endometrial cancer

    International Nuclear Information System (INIS)

    Purpose: Numerous studies have identified prognostic factors and failure patterns in stage I and clinical stage II endometrial cancer. These issues are less defined in pathologic stage II disease (pII) due to a paucity of patient data. Herein, we describe the prognostic significance of patient and tumor factors and patterns of failure in patients with pII disease. Methods/Materials: Fifty-three pts with pII (38 pIIA, 15 pIIB) endometrial cancer were treated between (6(80)) and (6(95)). Median age was 63 years (range, 35-90). Thirty-four pts (64%) were White, 16 (30%) Black and 3 (6%) Hispanic. Most tumors were pure adenocarcinoma (ACA) (66%) and grade 2-3 (77%). All patients underwent TAH-BSO. Nodal sampling and peritoneal washings were performed in 72% and 76%, respectively. Forty-eight (91%) received postoperative external beam pelvic (EBRT) +/- intracavitary RT (ICRT). Patient age ( 60), race (black vs other), stage (pIIA v pIIB), histology (ACA v other), myometrial invasion ( 50%) and grade ((1(2)) v 3) were evaluated. Sites of failure were defined as vaginal cuff, pelvis, para-aortic, and distant. Median followup was 40 months (range, 11-159 months) with 25% of pts followed for > 10 years. Results: The 5-year actuarial vaginal (VC), pelvic (PC) and para-aortic (PAC) controls for the entire group were 86.2%, 95.4% and 89.2%, respectively. The 5-year distant-free (DistFS), disease-free (DFS) and cause-specific (CSS) survivals were 79.6%, 63.7% and 77.5%, respectively. Conclusion: Our results demonstrate the prognostic significance of race and myometrial invasion as well as confirm the significance of stage, histology and grade in pII disease. Postoperative RT is associated with excellent locoregional control in these pts with the predominance of failure in para-aortic and distant sites

  7. An 8-gene qRT-PCR-based gene expression score that has prognostic value in early breast cancer

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    Cejas Paloma

    2010-06-01

    Full Text Available Abstract Background Gene expression profiling may improve prognostic accuracy in patients with early breast cancer. Our objective was to demonstrate that it is possible to develop a simple molecular signature to predict distant relapse. Methods We included 153 patients with stage I-II hormonal receptor-positive breast cancer. RNA was isolated from formalin-fixed paraffin-embedded samples and qRT-PCR amplification of 83 genes was performed with gene expression assays. The genes we analyzed were those included in the 70-Gene Signature, the Recurrence Score and the Two-Gene Index. The association among gene expression, clinical variables and distant metastasis-free survival was analyzed using Cox regression models. Results An 8-gene prognostic score was defined. Distant metastasis-free survival at 5 years was 97% for patients defined as low-risk by the prognostic score versus 60% for patients defined as high-risk. The 8-gene score remained a significant factor in multivariate analysis and its performance was similar to that of two validated gene profiles: the 70-Gene Signature and the Recurrence Score. The validity of the signature was verified in independent cohorts obtained from the GEO database. Conclusions This study identifies a simple gene expression score that complements histopathological prognostic factors in breast cancer, and can be determined in paraffin-embedded samples.

  8. An 8-gene qRT-PCR-based gene expression score that has prognostic value in early breast cancer

    International Nuclear Information System (INIS)

    Gene expression profiling may improve prognostic accuracy in patients with early breast cancer. Our objective was to demonstrate that it is possible to develop a simple molecular signature to predict distant relapse. We included 153 patients with stage I-II hormonal receptor-positive breast cancer. RNA was isolated from formalin-fixed paraffin-embedded samples and qRT-PCR amplification of 83 genes was performed with gene expression assays. The genes we analyzed were those included in the 70-Gene Signature, the Recurrence Score and the Two-Gene Index. The association among gene expression, clinical variables and distant metastasis-free survival was analyzed using Cox regression models. An 8-gene prognostic score was defined. Distant metastasis-free survival at 5 years was 97% for patients defined as low-risk by the prognostic score versus 60% for patients defined as high-risk. The 8-gene score remained a significant factor in multivariate analysis and its performance was similar to that of two validated gene profiles: the 70-Gene Signature and the Recurrence Score. The validity of the signature was verified in independent cohorts obtained from the GEO database. This study identifies a simple gene expression score that complements histopathological prognostic factors in breast cancer, and can be determined in paraffin-embedded samples

  9. The prognostic relevance of estimates of proliferative activity in early breast cancer

    DEFF Research Database (Denmark)

    Offersen, B V; Sørensen, Flemming Brandt; Knoop, A; Overgaard, J

    2003-01-01

    AIMS: Immunohistochemical estimates of cell proliferation evaluated with MIB-1 antibody have been suggested as prognostic indicators in different types of carcinoma. This study investigates whether MIB-1 scores add additional prognostic impact when evaluated together with classical clinicopatholo...

  10. The MyD88+ phenotype is an adverse prognostic factor in epithelial ovarian cancer.

    LENUS (Irish Health Repository)

    d'Adhemar, Charles J

    2014-01-01

    The prognosis of epithelial ovarian cancer is poor in part due to the high frequency of chemoresistance. Recent evidence points to the Toll-like receptor-4 (TLR4), and particularly its adaptor protein MyD88, as one potential mediator of this resistance. This study aims to provide further evidence that MyD88 positive cancer cells are clinically significant, stem-like and reproducibly detectable for the purposes of prognostic stratification. Expression of TLR4 and MyD88 was assessed immunohistochemically in 198 paraffin-embedded ovarian tissues and in an embryonal carcinoma model of cancer stemness. In parallel, expression of TLR4 and MyD88 mRNA and regulatory microRNAs (miR-21 and miR-146a) was assessed, as well as in a series of chemosensitive and resistant cancer cells lines. Functional analysis of the pathway was assessed in chemoresistant SKOV-3 ovarian cancer cells. TLR4 and MyD88 expression can be reproducibly assessed via immunohistochemistry using a semi-quantitative scoring system. TLR4 expression was present in all ovarian epithelium (normal and neoplastic), whereas MyD88 was restricted to neoplastic cells, independent of tumour grade and associated with reduced progression-free and overall survival, in an immunohistological specific subset of serous carcinomas, p<0.05. MiR-21 and miR-146a expression was significantly increased in MyD88 negative cancers (p<0.05), indicating their participation in regulation. Significant alterations in MyD88 mRNA expression were observed between chemosensitive and chemoresistant cells and tissue. Knockdown of TLR4 in SKOV-3 ovarian cells recovered chemosensitivity. Knockdown of MyD88 alone did not. MyD88 expression was down-regulated in differentiated embryonal carcinoma (NTera2) cells, supporting the MyD88+ cancer stem cell hypothesis. Our findings demonstrate that expression of MyD88 is associated with significantly reduced patient survival and altered microRNA levels and suggest an intact\\/functioning TLR4\\/MyD88

  11. Insulin Receptor Substrate Adaptor Proteins Mediate Prognostic Gene Expression Profiles in Breast Cancer

    Science.gov (United States)

    Becker, Marc A.; Ibrahim, Yasir H.; Oh, Annabell S.; Fagan, Dedra H.; Byron, Sara A.; Sarver, Aaron L.; Lee, Adrian V.; Shaw, Leslie M.; Fan, Cheng; Perou, Charles M.; Yee, Douglas

    2016-01-01

    Therapies targeting the type I insulin-like growth factor receptor (IGF-1R) have not been developed with predictive biomarkers to identify tumors with receptor activation. We have previously shown that the insulin receptor substrate (IRS) adaptor proteins are necessary for linking IGF1R to downstream signaling pathways and the malignant phenotype in breast cancer cells. The purpose of this study was to identify gene expression profiles downstream of IGF1R and its two adaptor proteins. IRS-null breast cancer cells (T47D-YA) were engineered to express IRS-1 or IRS-2 alone and their ability to mediate IGF ligand-induced proliferation, motility, and gene expression determined. Global gene expression signatures reflecting IRS adaptor specific and primary vs. secondary ligand response were derived (Early IRS-1, Late IRS-1, Early IRS-2 and Late IRS-2) and functional pathway analysis examined. IRS isoforms mediated distinct gene expression profiles, functional pathways, and breast cancer subtype association. For example, IRS-1/2-induced TGFb2 expression and blockade of TGFb2 abrogated IGF-induced cell migration. In addition, the prognostic value of IRS proteins was significant in the luminal B breast tumor subtype. Univariate and multivariate analyses confirmed that IRS adaptor signatures correlated with poor outcome as measured by recurrence-free and overall survival. Thus, IRS adaptor protein expression is required for IGF ligand responses in breast cancer cells. IRS-specific gene signatures represent accurate surrogates of IGF activity and could predict response to anti-IGF therapy in breast cancer. PMID:26991655

  12. Metastatic spinal cord compression in non-small cell lung cancer patients. Prognostic factors in a series of 356 patients

    Energy Technology Data Exchange (ETDEWEB)

    Rades, D.; Douglas, S. [Luebeck Univ. (Germany). Dept. of Radiation Oncology; Veninga, T. [Dr. Bernard Verbeeten Institute Tilburg (Netherlands). Dept. of Radiation Oncology; Bajrovic, A. [University Medical Center Hamburg-Eppendorf, Hamburg (Germany). Dept. of Radiation Oncology; Stalpers, L.J.A. [Academic Medical Center Amsterdam (Netherlands). Dept. of Radiotherapy; Hoskin, P.J. [Mount Vernon Centre for Cancer Treatment, Northwood (United Kingdom). Dept. of Clinical Oncology; Rudat, V. [Saad Specialist Hospital Al-Khobar (Saudi Arabia). Dept. of Radiation Oncology; Schild, S.E. [Mayo Clinic Scottsdale, Scottsdale, AZ (United States). Dept. of Radiation Oncology

    2012-06-15

    Patients with metastatic spinal cord compression (MSCC) from non-small cell lung cancer (NSCLC) have an unfavorable prognosis compared to most other MSCC patients. This study was performed to identify prognostic factors for functional outcome and survival in these patients after radiotherapy (RT) alone. Data of 356 patients irradiated for MSCC from NSCLC were retrospectively analyzed. Ten potential prognostic factors were investigated including age, gender, Eastern cooperative Oncology Group performance score (ECOG-PS), number of involved vertebrae, pre-RT ambulatory status, other bone metastases, visceral metastases, interval from cancer diagnosis to RT of MSCC, time developing motor deficits before RT, and the radiation schedule. On multivariate analysis, better functional outcome was associated with pre-RT ambulatory status (estimate: -0.84, p = 0.022), no visceral metastases (estimate: -1.15, p < 0.001), interval from cancer diagnosis to RT of > 15 months (estimate: +0.48, p = 0.019), and slower (> 7 days) development of motor deficits (estimate: +1.56, p < 0.001). On multivariate analysis, improved survival was significantly associated with female gender (risk ratio (RR) 1.32, p = 0.043), ECOG-PS 1-2 (RR 1.45, p = 0.034), pre-RT ambulatory status (RR 0.58, p < 0.001), no other bone metastases (RR 1.38, p = 0.010), no visceral metastases (RR 2.87, p < 0.001), interval from cancer diagnosis to RT of > 15 months (RR 0.84, p = 0.035), and slower (> 7 days) development of motor deficits (RR 0.78, p < 0.001). This study identified additional independent prognostic factors for outcomes after radiotherapy of MSCC from NSCLC. These prognostic factors can be used for stratification in future trials and can help develop prognostic scores for MSCC from NSCLC. (orig.)

  13. Prealbumin/CRP Based Prognostic Score, a New Tool for Predicting Metastasis in Patients with Inoperable Gastric Cancer.

    Science.gov (United States)

    Esfahani, Ali; Makhdami, Nima; Faramarzi, Elnaz; Asghari Jafarabadi, Mohammad; Ostadrahimi, Alireza; Ghayour Nahand, Mousa; Ghoreishi, Zohreh

    2016-01-01

    Background. There is a considerable dissimilarity in the survival duration of the patients with gastric cancer. We aimed to assess the systemic inflammatory response (SIR) and nutritional status of these patients before the commencement of chemotherapy to find the appropriate prognostic factors and define a new score for predicting metastasis. Methods. SIR was assessed using Glasgow Prognostic Score (GPS). Then a score was defined as prealbumin/CRP based prognostic score (PCPS) to be compared with GPS for predicting metastasis and nutritional status. Results. 71 patients with gastric cancer were recruited in the study. 87% of patients had malnutrition. There was a statistical difference between those with metastatic (n = 43) and those with nonmetastatic (n = 28) gastric cancer according to levels of prealbumin and CRP; however they were not different regarding patient generated subjective global assessment (PG-SGA) and GPS. The best cut-off value for prealbumin was determined at 0.20 mg/dL and PCPS could predict metastasis with 76.5% sensitivity, 63.6% specificity, and 71.4% accuracy. Metastatic and nonmetastatic gastric cancer patients were different in terms of PCPS (P = 0.005). Conclusion. PCPS has been suggested for predicting metastasis in patients with gastric cancer. Future studies with larger sample size have been warranted. PMID:26904109

  14. Prealbumin/CRP Based Prognostic Score, a New Tool for Predicting Metastasis in Patients with Inoperable Gastric Cancer

    Directory of Open Access Journals (Sweden)

    Ali Esfahani

    2016-01-01

    Full Text Available Background. There is a considerable dissimilarity in the survival duration of the patients with gastric cancer. We aimed to assess the systemic inflammatory response (SIR and nutritional status of these patients before the commencement of chemotherapy to find the appropriate prognostic factors and define a new score for predicting metastasis. Methods. SIR was assessed using Glasgow Prognostic Score (GPS. Then a score was defined as prealbumin/CRP based prognostic score (PCPS to be compared with GPS for predicting metastasis and nutritional status. Results. 71 patients with gastric cancer were recruited in the study. 87% of patients had malnutrition. There was a statistical difference between those with metastatic (n=43 and those with nonmetastatic (n=28 gastric cancer according to levels of prealbumin and CRP; however they were not different regarding patient generated subjective global assessment (PG-SGA and GPS. The best cut-off value for prealbumin was determined at 0.20 mg/dL and PCPS could predict metastasis with 76.5% sensitivity, 63.6% specificity, and 71.4% accuracy. Metastatic and nonmetastatic gastric cancer patients were different in terms of PCPS (P=0.005. Conclusion. PCPS has been suggested for predicting metastasis in patients with gastric cancer. Future studies with larger sample size have been warranted.

  15. Development and independent validation of a prognostic assay for stage II colon cancer using formalin-fixed paraffin-embedded tissue.

    LENUS (Irish Health Repository)

    Kennedy, Richard D

    2011-12-10

    Current prognostic factors are poor at identifying patients at risk of disease recurrence after surgery for stage II colon cancer. Here we describe a DNA microarray-based prognostic assay using clinically relevant formalin-fixed paraffin-embedded (FFPE) samples.

  16. Invasive breast cancer in Argentine women: association between risk and prognostic factors with antigens of a peptidic and carbohydrate nature

    Directory of Open Access Journals (Sweden)

    Croce MV

    2011-12-01

    Full Text Available Sandra O Demichelis, Marina T Isla-Larrain, Luciano Cermignani, Cecilio G Alberdi, Amada Segal-Eiras, María Virginia CroceCentre of Basic and Applied Immunological Research, Faculty of Medical Sciences, National University of La Plata, La Plata, ArgentinaObjective: In breast cancer, several tumor markers have been identified. The marker most extensively associated with breast cancer is MUC1. The objective of the study was to analyze prognostic and risk factors in relation to tumor markers in order to clarify breast cancer biology. A total of 349 primary tumor samples and lymph nodes from breast cancer patients were studied. Risk and prognostic factors were considered. An immunohistochemical approach was applied and an extensive statistical analysis was performed, including frequency analysis and analysis of variance. Correlation among variables was performed with principal component analysis.Results: All the antigens showed an increased expression according to tumor size increment; moreover, sialyl Lewis x expression showed a significant increase in relation to disease stage, whereas Tn and TF presented a positive tendency. Vascular invasion was related to sialyl Lewis x expression and number of metastatic lymph nodes. Taking into account risk factors, when a patient had at least one child, Lewis antigens diminished their expression. In relation to breastfeeding, sialyl Lewis x expression diminished, although its apical expression increased.Conclusion: Associations between MUC1 and carbohydrate antigens and risk and prognostic factors show the complexity of the cellular biological behavior that these antigens modulate in breast cancer.Keywords: breast cancer, Argentine women, risk factors, prognostic factors, antigenic expression

  17. Computerized three-class classification of MRI-based prognostic markers for breast cancer

    International Nuclear Information System (INIS)

    The purpose of this study is to investigate whether computerized analysis using three-class Bayesian artificial neural network (BANN) feature selection and classification can characterize tumor grades (grade 1, grade 2 and grade 3) of breast lesions for prognostic classification on DCE-MRI. A database of 26 IDC grade 1 lesions, 86 IDC grade 2 lesions and 58 IDC grade 3 lesions was collected. The computer automatically segmented the lesions, and kinetic and morphological lesion features were automatically extracted. The discrimination tasks-grade 1 versus grade 3, grade 2 versus grade 3, and grade 1 versus grade 2 lesions-were investigated. Step-wise feature selection was conducted by three-class BANNs. Classification was performed with three-class BANNs using leave-one-lesion-out cross-validation to yield computer-estimated probabilities of being grade 3 lesion, grade 2 lesion and grade 1 lesion. Two-class ROC analysis was used to evaluate the performances. We achieved AUC values of 0.80 ± 0.05, 0.78 ± 0.05 and 0.62 ± 0.05 for grade 1 versus grade 3, grade 1 versus grade 2, and grade 2 versus grade 3, respectively. This study shows the potential for (1) applying three-class BANN feature selection and classification to CADx and (2) expanding the role of DCE-MRI CADx from diagnostic to prognostic classification in distinguishing tumor grades.

  18. Cyclin D1 expression in colorectal cancer is a favorable prognostic factor in men but not in women in a prospective, population-based cohort study

    Directory of Open Access Journals (Sweden)

    Wangefjord Sakarias

    2011-09-01

    Full Text Available Abstract Background Although colorectal cancer (CRC is generally not considered to be a hormone-dependent malignancy, several sex-related differences in incidence, molecular characteristics and survival have been reported. Epidemiological studies have consistently shown that increased exposure to female sex hormones is associated with a lower risk of CRC in women, and cyclin D1, an important downstream effector in estrogen-mediated signaling, is commonly activated in CRC. In this study, we analyzed the prognostic significance of cyclin D1 expression in CRC, with particular reference to sex-related differences, in tumors from a large, prospective, population-based cohort. Methods Using tissue microarrays and immunohistochemistry, the fraction and intensity of cyclin D1 expression was evaluated in 527 incident CRC cases from the Malmö Diet and Cancer Study. The χ2 and Spearman's rho (ρ tests were used for comparison of cyclin D1 expression and relevant clinicopathological characteristics. Kaplan-Meier analysis and Cox proportional hazards modeling were used to assess the effect of cyclin D1 expression on cancer-specific survival (CSS in univariate and multivariate analysis, adjusted for established prognostic factors. Results Cyclin D1 intensity was significantly lower in male compared with female CRC (P = 0.018. In the full cohort, cyclin D1 expression was associated with a significantly prolonged CSS (hazard ratio (HR = 0.69; 95% CI 0.49 to 0.96, P = 0.026 but subgroup analysis according to gender revealed a strongly accentuated prognostic effect of cyclin D1 in male CRC (HR = 0.48; 95% CI 0.31 to 0.74, P P = 0.864 (Pinteraction = 0.024. The prognostic value of cyclin D1 was not retained in multivariate analysis, either in the full cohort or in male CRC. Conclusions Cyclin D1 expression is strongly associated with prolonged survival in male CRC. These findings not only support an important role for cyclin D1 in colorectal carcinogenesis, but

  19. The Roles of MicroRNAs in Breast Cancer

    International Nuclear Information System (INIS)

    MicroRNAs (miRNAs) constitute a large family of small, approximately 20–22 nucleotide, non-coding RNAs that regulate the expression of target genes, mainly at the post-transcriptional level. Accumulating lines of evidence have indicated that miRNAs play important roles in the maintenance of biological homeostasis and that aberrant expression levels of miRNAs are associated with the onset of many diseases, including cancer. In various cancers, miRNAs play important roles in tumor initiation, drug resistance and metastasis. Recent studies reported that miRNAs could also be secreted via small endosome-derived vesicles called exosomes, which are derived from multiple cell types, including dendritic cells, lymphocytes, and tumor cells. Exosomal miRNAs play an important role in cell-to-cell communication and have been investigated as prognostic and diagnostic biomarkers. In this review, we summarize the major findings related to the functions of miRNAs in breast cancer, which is the most frequent cancer in women, and discuss the potential clinical uses of miRNAs, including their roles as therapeutic targets and diagnostic markers

  20. The Roles of MicroRNAs in Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Ryou-u [Division of Molecular and Cellular Medicine, National Cancer Center Research Institute 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045 (Japan); Miyazaki, Hiroaki [Division of Molecular and Cellular Medicine, National Cancer Center Research Institute 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045 (Japan); Department of Oral and Maxillofacial Surgery, Showa University School of Dentistry, 1-5-8 Hatanodai Shinagawa-ku, Tokyo 142-8555 (Japan); Ochiya, Takahiro, E-mail: tochiya@ncc.go.jp [Division of Molecular and Cellular Medicine, National Cancer Center Research Institute 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045 (Japan)

    2015-04-09

    MicroRNAs (miRNAs) constitute a large family of small, approximately 20–22 nucleotide, non-coding RNAs that regulate the expression of target genes, mainly at the post-transcriptional level. Accumulating lines of evidence have indicated that miRNAs play important roles in the maintenance of biological homeostasis and that aberrant expression levels of miRNAs are associated with the onset of many diseases, including cancer. In various cancers, miRNAs play important roles in tumor initiation, drug resistance and metastasis. Recent studies reported that miRNAs could also be secreted via small endosome-derived vesicles called exosomes, which are derived from multiple cell types, including dendritic cells, lymphocytes, and tumor cells. Exosomal miRNAs play an important role in cell-to-cell communication and have been investigated as prognostic and diagnostic biomarkers. In this review, we summarize the major findings related to the functions of miRNAs in breast cancer, which is the most frequent cancer in women, and discuss the potential clinical uses of miRNAs, including their roles as therapeutic targets and diagnostic markers.

  1. The Largest Known Survival Analysis of Patients with Brain Metastasis from Thyroid Cancer Based on Prognostic Groups.

    Directory of Open Access Journals (Sweden)

    Jinhyun Choi

    Full Text Available To analyze the clinical features and prognostic factors associated with the survival of patients with a very rare occurrence of brain metastasis (BM from differentiated thyroid cancer (DTC.A total of 37 patients with DTC who were diagnosed with BM between 1995 and 2014 were included. We reviewed the clinical characteristics, treatment modalities, and image findings of BM. Factors associated with survival were evaluated, and the patients were divided into three prognostic groups (Groups A, B, and C for comparative analysis.The median age at BM was 63 years, and the median time from initial thyroid cancer diagnosis to BM was 3.8 years. The median survival and the 1-year actuarial survival rate after BM were 8.8 months and 47%, respectively. According to univariate and multivariate analyses, four good prognostic factors (GPFs were identified including age ≤ 60 years, PS ≤ ECOG 2, ≤ 3 BM sites, and without extracranial metastasis prior to BM. Three prognostic groups were designed based on age and number of remaining GPFs: patients ≤ 60 years of age with at least 2 GPFs (Group A had the most favorable prognosis with a median survival of 32.8 months; patients ≤ 60 years of age with fewer than 2 GPFs and those > 60 years of age with at least 2 GPFs (Group B had an intermediate prognosis with a median survival of 9.4 months; and patients > 60 years of age with fewer than 2 GPFs (Group C had the least favorable prognosis with a median survival of 1.5 months.The survival of patients with BM form DTC differed among the prognostic groups based on the total number of good prognostic factors.

  2. The Largest Known Survival Analysis of Patients with Brain Metastasis from Thyroid Cancer Based on Prognostic Groups

    Science.gov (United States)

    Choi, Jinhyun; Kim, Jun Won; Keum, Yo Sup; Lee, Ik Jae

    2016-01-01

    Purpose To analyze the clinical features and prognostic factors associated with the survival of patients with a very rare occurrence of brain metastasis (BM) from differentiated thyroid cancer (DTC). Methods and Materials A total of 37 patients with DTC who were diagnosed with BM between 1995 and 2014 were included. We reviewed the clinical characteristics, treatment modalities, and image findings of BM. Factors associated with survival were evaluated, and the patients were divided into three prognostic groups (Groups A, B, and C) for comparative analysis. Results The median age at BM was 63 years, and the median time from initial thyroid cancer diagnosis to BM was 3.8 years. The median survival and the 1-year actuarial survival rate after BM were 8.8 months and 47%, respectively. According to univariate and multivariate analyses, four good prognostic factors (GPFs) were identified including age ≤ 60 years, PS ≤ ECOG 2, ≤ 3 BM sites, and without extracranial metastasis prior to BM. Three prognostic groups were designed based on age and number of remaining GPFs: patients ≤ 60 years of age with at least 2 GPFs (Group A) had the most favorable prognosis with a median survival of 32.8 months; patients ≤ 60 years of age with fewer than 2 GPFs and those > 60 years of age with at least 2 GPFs (Group B) had an intermediate prognosis with a median survival of 9.4 months; and patients > 60 years of age with fewer than 2 GPFs (Group C) had the least favorable prognosis with a median survival of 1.5 months. Conclusions The survival of patients with BM form DTC differed among the prognostic groups based on the total number of good prognostic factors. PMID:27128487

  3. Prognostic Value of Residual Disease after Interval Debulking Surgery for FIGO Stage IIIC and IV Epithelial Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Marianne J. Rutten

    2015-01-01

    Full Text Available Although complete debulking surgery for epithelial ovarian cancer (EOC is more often achieved with interval debulking surgery (IDS following neoadjuvant chemotherapy (NACT, randomized evidence shows no long-term survival benefit compared to complete primary debulking surgery (PDS. We performed an observational cohort study of patients treated with debulking surgery for advanced EOC to evaluate the prognostic value of residual disease after debulking surgery. All patients treated between 1998 and 2010 in three Dutch referral gynaecological oncology centres were included. The prognostic value of residual disease after surgery for disease specific survival was assessed using Cox-regression analyses. In total, 462 patients underwent NACT-IDS and 227 PDS. Macroscopic residual disease after debulking surgery was an independent prognostic factor for survival in both treatment modalities. Yet, residual tumour less than one centimetre at IDS was associated with a survival benefit of five months compared to leaving residual tumour more than one centimetre, whereas this benefit was not seen after PDS. Leaving residual tumour at IDS is a poor prognostic sign as it is after PDS. The specific prognostic value of residual tumour seems to depend on the clinical setting, as minimal instead of gross residual tumour is associated with improved survival after IDS, but not after PDS.

  4. Role of cancer stem cells in hepatocarcinogenesis

    OpenAIRE

    Wang, Bo; Jacob, Samson T.

    2011-01-01

    There has been considerable interest in cancer stem cells (CSCs) among cancer biologists and clinicians, most likely because of their role in the heterogeneity of cancer and their potential application in cancer therapeutics. Recent studies suggest that CSCs play a key role in liver carcinogenesis. A small subpopulation of cancer cells with CSC properties has been identified and characterized from hepatocellular carcinoma (HCC) cell lines, animal models and human primary HCCs. Considering the...

  5. PTK 7 is a transforming gene and prognostic marker for breast cancer and nodal metastasis involvement.

    Directory of Open Access Journals (Sweden)

    Silvia Gärtner

    Full Text Available Protein Tyrosin Kinase 7 (PTK7 is upregulated in several human cancers; however, its clinical implication in breast cancer (BC and lymph node (LN is still unclear. In order to investigate the function of PTK7 in mediating BC cell motility and invasivity, PTK7 expression in BC cell lines was determined. PTK7 signaling in highly invasive breast cancer cells was inhibited by a dominant-negative PTK7 mutant, an antibody against the extracellular domain of PTK7, and siRNA knockdown of PTK7. This resulted in decreased motility and invasivity of BC cells. We further examined PTK7 expression in BC and LN tissue of 128 BC patients by RT-PCR and its correlation with BC related genes like HER2, HER3, PAI1, MMP1, K19, and CD44. Expression profiling in BC cell lines and primary tumors showed association of PTK7 with ER/PR/HER2-negative (TNBC-triple negative BC cancer. Oncomine data analysis confirmed this observation and classified PTK7 in a cluster with genes associated with agressive behavior of primary BC. Furthermore PTK7 expression was significantly different with respect to tumor size (ANOVA, p = 0.033 in BC and nodal involvement (ANOVA, p = 0.007 in LN. PTK7 expression in metastatic LN was related to shorter DFS (Cox Regression, p = 0.041. Our observations confirmed the transforming potential of PTK7, as well as its involvement in motility and invasivity of BC cells. PTK7 is highly expressed in TNBC cell lines. It represents a novel prognostic marker for BC patients and has potential therapeutic significance.

  6. PTK 7 is a transforming gene and prognostic marker for breast cancer and nodal metastasis involvement.

    Science.gov (United States)

    Gärtner, Silvia; Gunesch, Angela; Knyazeva, Tatiana; Wolf, Petra; Högel, Bernhard; Eiermann, Wolfgang; Ullrich, Axel; Knyazev, Pjotr; Ataseven, Beyhan

    2014-01-01

    Protein Tyrosin Kinase 7 (PTK7) is upregulated in several human cancers; however, its clinical implication in breast cancer (BC) and lymph node (LN) is still unclear. In order to investigate the function of PTK7 in mediating BC cell motility and invasivity, PTK7 expression in BC cell lines was determined. PTK7 signaling in highly invasive breast cancer cells was inhibited by a dominant-negative PTK7 mutant, an antibody against the extracellular domain of PTK7, and siRNA knockdown of PTK7. This resulted in decreased motility and invasivity of BC cells. We further examined PTK7 expression in BC and LN tissue of 128 BC patients by RT-PCR and its correlation with BC related genes like HER2, HER3, PAI1, MMP1, K19, and CD44. Expression profiling in BC cell lines and primary tumors showed association of PTK7 with ER/PR/HER2-negative (TNBC-triple negative BC) cancer. Oncomine data analysis confirmed this observation and classified PTK7 in a cluster with genes associated with agressive behavior of primary BC. Furthermore PTK7 expression was significantly different with respect to tumor size (ANOVA, p = 0.033) in BC and nodal involvement (ANOVA, p = 0.007) in LN. PTK7 expression in metastatic LN was related to shorter DFS (Cox Regression, p = 0.041). Our observations confirmed the transforming potential of PTK7, as well as its involvement in motility and invasivity of BC cells. PTK7 is highly expressed in TNBC cell lines. It represents a novel prognostic marker for BC patients and has potential therapeutic significance. PMID:24409301

  7. Prognostic impact of serum albumin levels on the recurrence of stage I non-small cell lung cancer

    OpenAIRE

    Ying Jin; Li Zhao; Fang Peng

    2013-01-01

    Objective: Patients with stage I non-small cell lung cancer who have undergone complete surgical resection harbor a 30% risk for tumor recurrence. Thus, the identification of factors that are predictive for tumor recurrence is urgently needed. The aim of this study was to test the prognostic value of serum albumin levels on tumor recurrence in patients with stage I non-small cell lung cancer. Methods: Stage I non-small cell lung cancer patients who underwent complete surgical resection of the...

  8. β 2 microglobulin mRNA expression levels are prognostic for lymph node metastasis in colorectal cancer patients

    OpenAIRE

    Shrout, J; M. Yousefzadeh; Dodd, A; Kirven, K; C. Blum; Graham, A; Benjamin, K; Hoda, R; M. Krishna; Romano, M.; Wallace, M.; Garrett-Mayer, E; Mitas, M

    2008-01-01

    Colorectal cancer (CRC) is the fourth most common non-cutaneous malignancy in the United States and the second most frequent cause of cancer-related death. One of the most important determinants of CRC survival is lymph node metastasis. To determine whether molecular markers might be prognostic for lymph node metastases, we measured by quantitative real-time RT–PCR the expression levels of 15 cancer-associated genes in formalin-fixed paraffin-embedded primary tissues derived from stage I–IV C...

  9. Prognostic factors of early breast cancer treated with radiation after radical mastectomy

    International Nuclear Information System (INIS)

    Objective: To study whether post-operative radiotherapy is necessary for patients with early breast cancer after radical mastectomy. Methods: In 1998, 270 early breast cancer patients with 0 -3 pathologically confirmed positive axillary lymph nodes after radical mastectomy were retrospectively analyzed. There were 156 patients with negative lymph node and 114 with 1 -3 positive lymph nodes. The prognostic index (PI) was defined as the sum of scores of the tumor size, number of positive axillary lymph nodes, receptor status, surgical margin status, lymphatic thrombi status, pathological grading and age. The PI≥ 4 was considered as high-risk, and PI 2 = 4.40, P =0.036), respectively. The corresponding disease-free survival rate, local recurrence rate, distant metastasis rate were 71.2% and 9.6% (χ2=3.90, P=0.048), 7.7% and 16.7% (χ2=5.22, P=0.022), 12.8% and 21.1%(χ2=3.27, P=0.070), respectively. The mean dis-ease-free survival time of the two groups was 97.03±2.53 months and 87.01±3.80 months, respectively. In the high-risk group, the 10-year survival rates of patients with and without radiotherapy were 72% and 56% (χ2=4.07, P=0.044), the local recurrence rates were 5% and 24% (χ2=11.16, P=0.001), and the distant metastasis rates were 16% and 26% (χ2=2.18, P=0.140). In the low-risk group, the survival rate of patients with and without radiotherapy were 81% and 71% (χ2 =1.57, P=0.210), the local recurrence rates were both 11% (χ2=0.01, P=0.975), and the distant metastasis rates were both 13% (χ2 =0.00, P=1.000). Conclusions: Early breast cancer patients with 1 -3 positive axillary lymph nodes should receive post-operative radiotherapy after radical mastectomy. The prognostic index may decrease the chance of unnecessary radiation by distinguishing the patients under low risk of recurrence from those under high risk. (authors)

  10. Prognostic significance of local recurrence in breast cancer after postmastectomy radiotherapy

    International Nuclear Information System (INIS)

    Purpose: We have retrospectively analyzed the impact of local recurrence in patients with adjuvant radiation therapy after mastectomy for breast cancer. Patients and Methods: From January 1985 through December 1993, 959 patients were irradiated after mastectomy for breast cancer. The age ranged from 34 to 79 years, the median follow-up was 3.1 years (range; 0.3-12.2 years). 368 (38%) were pre- and 591 (62%) postmenopausal. 35% had T3-4 tumors, 62% had axillary lymph node involvement, and 66% received additional systemic hormonal and/or cytotoxic therapy. Postmastectomy radiotherapy was administered in case of positive axillary nodes and in high-risk pN0-patients. The chest wall and lymphatics (axilla, parasternal and supraclavicular nodes) were irradiated with an anterior photon field with 50 Gy and the chest wall with an electron field with 44 Gy in 2-Gy fractions. Results: The overall survival was 70.5% after 5 and 59.8% after 10 years. 53 patients (5.5%) developed a locoregional recurrence 2-96 months after treatment (median 26 months). The local control rate was 92.7% after 5 and 86.4% after 10 years. Axillary lymph node involvement was the most important and (in a multivariate analysis the only) risk factor for local recurrence (p=0.0001). Patients with local control had a significantly better 10-year distant-disease-free survival and overall survival as compared to patients with local recurrence (44.5% vs 15.4%, p=0.002 and 62.1% vs 34.8%, p=0.004). Local recurrence increased the risk of death by a factor of 1.7 and in a Cox regression model, axillary lymph node status, T-category and local recurrence were significant prognostic factors for overall survival. In patients with local recurrence, the initial axillary lymph node status was the most important prognostic factor for survival after local recurrence. The 3-year survival after local relapse was 86% for patients with pN0 status vs 27% in with positive axillary nodes (p=0.025). Conclusions: Local

  11. Gene expression classification of colon cancer into molecular subtypes: characterization, validation, and prognostic value.

    Directory of Open Access Journals (Sweden)

    Laetitia Marisa

    -free survival, even after adjusting for age, sex, stage, and the emerging prognostic classifier Oncotype DX Colon Cancer Assay recurrence score (hazard ratio 1.5, 95% CI 1.1-2.1, p = 0.0097. However, a limitation of this study is that information on tumor grade and number of nodes examined was not available. CONCLUSIONS: We describe the first, to our knowledge, robust transcriptome-based classification of CC that improves the current disease stratification based on clinicopathological variables and common DNA markers. The biological relevance of these subtypes is illustrated by significant differences in prognosis. This analysis provides possibilities for improving prognostic models and therapeutic strategies. In conclusion, we report a new classification of CC into six molecular subtypes that arise through distinct biological pathways.

  12. Prognostic impact of metastatic lymph node ratio in advanced gastric cancer from cardia and fundus

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    AIM: To investigate the prognostic impact of the metastatic lymph node ratio (MLR) in advanced gastric cancer from the cardia and fundus. METHODS: Two hundred and thirty-six patients with gastric cancer from the cardia and fundus who underwent D2 curative resection were analyzed ret- rospectively. The correlations between MLR and the total lymph nodes, positive nodes and the total lymph nodes were analyzed respectively. The influence of MLR on the survival time of patients was determined with univariate Kaplan-Meier survival analysis and mul- tivariate Cox proportional hazard model analysis. And the multiple linear regression was used to identify the relation between MLR and the 5-year survival rate of the patients. RESULTS: The MLR did not correlate with the total lymph nodes resected (r = -0.093, P = 0.057). The 5-year overall survival rate of the whole cohort was 37.5%. Kaplan-Meier survival analysis identified that the following eight factors influenced the survival time of the patients postoperatively: gender (X2 = 4.26, P = 0.0389), tumor size (X2 = 18.48, P < 0.001), Borrmann type (X2 = 7.41, P = 0.0065), histological grade (X2 =5.07, P = 0.0243), pT category (X2 = 49.42, P < 0.001), pN category (X2 = 87.7, P < 0.001), total number of re- trieved lymph nodes (X2 = 8.22, P = 0.0042) and MLR (X2 = 34.3, P < 0.001). Cox proportional hazard model showed that tumor size (X2 = 7.985, P = 0.018), pT category (X2 = 30.82, P < 0.001) and MLR (X2 = 69.39, P < 0.001) independently influenced the prognosis. A linear correlation between MLR and the 5-year survival was statistically significant based on the multiple lin- ear regression (β = -0.63, P < 0.001). Hypothetically, the 5-year survival would surpass 50% when MLR was lower than 10%. CONCLUSION: The MLR is an independent prognostic factor for patients with advanced gastric cancer from the cardia and fundus. The decrease of MLR due to adequate number of total resected lymph nodes can improve the survival.

  13. Characteristics and prognostic factors for pain management in 152 patients with lung cancer

    Directory of Open Access Journals (Sweden)

    Shi L

    2016-04-01

    Full Text Available Lei Shi,1,* Yumei Liu,2,* Hua He,1 Cong Wang,1 Hongwei Li,1 Nanya Wang1 1Cancer Center, The First Hospital of Jilin University, Changchun, 2Department of Hematology, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China *These authors contributed equally to this work Objective: The objective of this study was to analyze the pain characteristics and factors influencing the outcome of pain control in patients with lung cancer having pain. Methods: Pain characteristics, the effectiveness, and prognostic factors for pain control were analyzed in 152 patients with lung cancer having moderate or severe chronic pain admitted to Cancer Center of The First Hospital of Jilin University, People’s Republic of China, between January 2012 and May 2013. Information about sex, age, pathological type, TNM stage, presence/absence of bone metastases, characteristics of pain, methods, and effectiveness of pain management was recorded. Results: Patients with non-small-cell lung cancer and small-cell carcinoma accounted for 132/152 (86.8% and 20/152 (13.2% cases, respectively. Among them, moderate (72.4% or severe pain (27.6% was reported in 73.7% of the cases at stage IV, chest or back pain was reported in 76.3% of the cases, and pain in other locations in the rest of the cases. Bone metastases were apparent in 44.1% of the patients. Neuropathic pain was noted in 46.7% of the patients, and frequent breakthrough pain was noted in 25.7% of the patients. High pain intensity was associated with frequent breakthrough pain. Pain was adequately controlled in 81.6% of the patients prescribed 3 days of analgesics. More patients reported a KPS higher than or equal to 80 after 3 days of analgesic treatment (P<0.001. Severe pain, frequent breakthrough pain, and presence of bone metastases were independent risk factors for poor pain control. Severe pain, frequent breakthrough pain, or neuropathic pain in the patients using opioids required higher

  14. Prognostic and predictive value of DAMPs and DAMP-associated processes in cancer

    Directory of Open Access Journals (Sweden)

    Jitka eFucikova

    2015-08-01

    Full Text Available It is now clear that human neoplasms form, progress and respond to therapy in the context of an intimate crosstalk with the host immune system. In particular, accumulating evidence demonstrates that the efficacy of most, if not all, chemo- and radiotherapeutic agents commonly employed in the clinic critically depends on the (reactivation of tumor-targeting immune response. One of the mechanisms whereby conventional chemotherapeutics, targeted anticancer agents and radiotherapy can provoke a therapeutically relevant, adaptive immune response against malignant cells is commonly known as „immunogenic cell death (ICD. Importantly, dying cancer cells are perceived as immunogenic only when they emit a set of immunostimulatory signals upon the activation of intracellular stress response pathways. The emission of these signals, which are generally referred to as „damage-associated molecular patterns (DAMPs, may therefore predict whether patients will respond to chemotherapy or not, at least in some settings. Here, we review clinical data indicating that DAMPs and DAMP-associated stress responses might have prognostic or predictive value for cancer patients.

  15. Natural History of Untreated Prostate Specific Antigen Radiorecurrent Prostate Cancer in Men with Favorable Prognostic Indicators

    Directory of Open Access Journals (Sweden)

    Neil E. Martin

    2014-01-01

    Full Text Available Background and Purpose. Life expectancy data could identify men with favorable post-radiation prostate-specific antigen (PSA failure kinetics unlikely to require androgen deprivation therapy (ADT. Materials and Methods. Of 206 men with unfavorable-risk prostate cancer in a randomized trial of radiation versus radiation and ADT, 53 experienced a PSA failure and were followed without salvage ADT. Comorbidity, age and established prognostic factors were assessed for relationship to death using Cox regression analyses. Results. The median age at failure, interval to PSA failure, and PSA doubling time were 76.6 years (interquartile range [IQR]: 71.8–79.3, 49.1 months (IQR: 37.7–87.4, and 25 months (IQR: 13.1–42.8, respectively. After a median follow up of 4.0 years following PSA failure, 45% of men had died, none from prostate cancer and no one had developed metastases. Both increasing age at PSA failure (HR: 1.14; 95% CI: 1.03–1.25; P=0.008 and the presence of moderate to severe comorbidity (HR: 12.5; 95% CI: 3.81–41.0; P2 years following post-radiation PSA failure appear to be good candidates for observation without ADT intervention.

  16. miR-1260b is a Potential Prognostic Biomarker in Colorectal Cancer.

    Science.gov (United States)

    Liu, Deng-Rui; Guan, Quan-Lin; Gao, Ming-Tai; Jiang, Lei; Kang, Hong-Xia

    2016-01-01

    BACKGROUND Colorectal cancer (CRC) mainly refers to colon and rectum cancer, which is the most common gastrointestinal malignant tumor. MicroRNAs (miRNAs) in tumors participate in multiple processes of malignancy development, including cell differentiation, proliferation, invasion, and metastasis. In this study we explored the relationship of miR-1260b abnormal expression with clinical pathological features in CRC patients. MATERIAL AND METHODS The expression of miR-1260b was detected by real-time quantitative polymerase chain reaction (real-time PCR) in 120 cases of CRC tissues. The correlation of miR-1260b expression with the clinicopathologic features of CRC was analyzed by SPSS 21.0 statistical software. The Kaplan-Meier method was used for survival analysis. Cox regression analyses were conducted to determine whether miR-1260b was an independent predictor of survival for CRC patients. RESULTS The miR-1260b expression in CRC was significantly higher than the expression levels in the corresponding para-carcinoma tissues (P0.05). The high miR-1260b expression patients survived for shorter times than those CRC patients with low miR-1260b expression (P<0.05). Multivariate analysis revealed that high miR-1260b means poor prognosis of patients with CRC. CONCLUSIONS The high expression level of miR-1260b is an independent prognostic biomarker that indicates a worse prognosis for patients with CRC. PMID:27399918

  17. The prognostic value of KRAS mutated plasma DNA in advanced non-small cell lung cancer

    DEFF Research Database (Denmark)

    Nygaard, Anneli Dowler; Garm Spindler, Karen-Lise; Pallisgaard, Niels;

    2013-01-01

    BACKGROUND: Lung cancer is one of the most common malignant diseases worldwide and associated with considerable morbidity and mortality. New agents targeting the epidermal growth factor system are emerging, but only a subgroup of the patients will benefit from the therapy. Cell free DNA (cf......DNA) in the blood allows for tumour specific analyses, including KRAS-mutations, and the aim of the study was to investigate the possible prognostic value of plasma mutated KRAS (pmKRAS) in patients with non-small cell lung cancer (NSCLC). MATERIAL AND METHODS: Patients with newly diagnosed, advanced NSCLC eligible......-KRAS mutation had a significantly shorter OS and PFS compared to the wild type (WT) patients (median OS 4.8 months versus 9.5 months, HR 1.87, 95% CI 1.23-2.84, p=0.0002 and median PFS 3.0 months versus 5.6 months, HR 1.60, 95% CI 1.09-2.37, p=0.0043). A multivariate Cox regression analysis confirmed...

  18. Prognostic impact of tumour-infiltrating B cells and plasma cells in colorectal cancer.

    Science.gov (United States)

    Berntsson, Jonna; Nodin, Björn; Eberhard, Jakob; Micke, Patrick; Jirström, Karin

    2016-09-01

    Multiple studies have described associations between infiltrating immune cells and prognosis in cancer; however, the clinical relevance has most often been attributed to the T-cell linage. This study aimed to further investigate the clinicopathological correlates and prognostic impact of B cell and plasma cell infiltration in CRC. Immunohistochemical expression of CD20, CD138 and immunoglobulin kappa C (IGKC) was analysed in tissue microarrays with tumours from 557 incident cases of CRC from a prospective population-based cohort. Kaplan-Meier analysis and Cox regression analysis were used to determine the impact of CD20, CD138 and IGKC expression on 5-year overall survival. Immune cell-specific CD20, CD138, and IGKC expression correlated significantly with lower T-stage (p stage, differentiation grade and vascular invasion (HR = 0.51; 95% CI 0.33-0.80). Immune cell-specific CD138 and IGKC expression correlated significantly with an improved OS in univariable Cox regression analysis; however, these associations did not remain significant in multivariable analysis. Finally, tumour cell-specific CD138 expression was found to be an independent factor of poor prognosis (HR 1.52; 95% CI 1.03-2.24). The results from the present study demonstrate that B cell infiltration in CRC has a significant impact on tumour progression and prognosis. These findings supplement and extend the current knowledge of the immune landscape in colorectal cancer, and merit further study. PMID:27074317

  19. Lipid peroxidation and antioxidants in different stages of cervical cancer: Prognostic significance

    Directory of Open Access Journals (Sweden)

    S Srivastava

    2009-01-01

    Full Text Available Background: Free radical Injury is associated with cancer, but how the extent of oxidative stress correlates with the FIGO (International Federation of Gynecology and Obstetrics stage in Carcinoma Cervix (Ca Cx, and its significance as a prognostic marker, is not clear and needs an in-depth study. Aim: To correlate the blood levels of Lipid Peroxidation (LPO, Reduced Glutathione (GSH, Superoxide Dismutase (SOD, and Vitamin A and E levels with the clinical stage in Ca Cx. Settings and Design: This is a Prospective Case Control Study. Materials and Methods: LPO, SOD, reduced GSH were estimated by Bio Chemical Assays and Vitamins by High Performance Liquid Chromatography (HPLC. Statistical Analysis: The cases and controls were compared using One Way ANOVA and different stages over different time periods were individually compared by Repeated Measure Analysis of Variance. Results: The results indicated a statistically significant increase of LPO vis-a-vis the FIGO stage of Ca Cx and control, while the antioxidant status as depicted by GSH and SOD decreased. Vitamin A and E levels were significantly lower in cancer cases as compared to the control. Conclusion: Increased LPO and reduced antioxidant levels may be taken as associated predictive markers, thus suggesting that Ca Cx cases should get nutritive supplements to contain the blood LPO level and maintain a positive balance of antioxidants for a better outcome in terms of delayed recurrence and better Quality of Life (QOL.

  20. An analysis of prognostic factors in the uterine cervical cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Dae Sik; Yoon, Won Sub; Kim, Tae Hyun; Kim, Chul Yong; Choi, Myung Sun [College of Medicine, Korea Univ., Seoul (Korea, Republic of)

    2000-12-01

    The aim of this study is to analysis of survival and recurrence rates of the uterine cervical carcinoma patients whom received the radiation therapy respectively. The prognostic factors, such as Papanicolaou (Pap) smear, carcinoembriogenic antigen (CEA) and squamous cell carcinoma (SCC) antigen has been studied. From January 1981 to December 1998, eight-hundred twenty-seven uterine cervical cancer patients were treated with radiation therapy. All of the patients were divided into two groups: the radiation therapy only (521 patients) group and the postoperative radiation therapy (326 patients) group. The age, treatment modality, clinical stage, histopathology, recurrence, follow-up Pap smears, CEA and see antigen were used as parameters for the evaluation. The prognostic factors such as survival and recurrence rates were performed with the Kaplan-Meier method and the Cox hazard model, respectively. Median fallow-up was 38.6 months. On the radiation therapy only group, 314 patients (60%) achieved complete response (CR), 47 patients (9%) showed local recurrence (LR), 78 patients (15%) developed distant metastasis (DM). On the postoperative radiation therapy group, showed 276 patients (85%) CR, 8 patients (2%) LR, 37 patients (11%) DM. The 5-year survival and recurrence rates was evaluated for all parameters. The statistically significant factors for the survival rate in univariate analysis were clinical stage (p=0.00001), treatment modality (p=0.0010), recurrence (p=0.0001), Pap smear (p=0.0329), CEA (p=0.0001) and SCC antigen (p=0.0001). This study indicated that after treatment, the follow-up studies of Pap smear, CEA and SCC antigen were significant parameter and prediction factors for the survival and recurrence of the uterine cervical carcinoma.

  1. Dynamic magnetic resonance imaging in determining histopathological prognostic factors of invasive breast cancers

    International Nuclear Information System (INIS)

    Objective: To evaluate the relation between morphological features and enhancement parameters in dynamic contrast-enhanced magnetic resonance (DCE-MR) imaging with histopathological prognostic factors. Materials and methods: Fifty-five patients with surgicopathological diagnosis of breast carcinoma were evaluated with 1.0 T MR scanner as a part of their preoperative diagnostic work-up. Dynamic studies were performed in axial plane using 3D fast low angle shot (FLASH) sequence. Time intensity curves (TICs) were obtained from the regions showing maximal enhancement in subtraction images. The correlations between enhancement parameters and histopathological findings were analyzed using stepwise multiple regression analysis, Student's t-test, χ2-tests and Pearson's moment correlation coefficient. Results: Significant correlations were found between the presence of lymph node metastasis and tumor size (P<0.05) and edge characteristics (P<0.05). A highly significant correlation was found between histopathological grades and qualitative enhancement patterns (r=0.403, P<0.01). Statistically significant differences were found between the groups with and without lymph node metastasis regarding enhancement in the first minute (P<0.01) and TIC slope (P<0.05). A significant difference was found between the histopathological grades I and III regarding all quantitative enhancement parameters, whereas no difference was found between the grades I-II, and II-III. Conclusion: DCE-MR imaging helps to predict prognostic factors of breast cancer by revealing morphological features and enhancement parameters of the primary tumor. Additional morphological factors further improve our ability to predict lymphatic metastasis

  2. Outcome and Prognostic Factors in Endometrial Stromal Tumors: A Rare Cancer Network Study

    International Nuclear Information System (INIS)

    Purpose: To provide further understanding regarding outcome and prognostic factors of endometrial stromal tumors (EST). Methods and Materials: A retrospective analysis was performed on the records of 59 women diagnosed with EST and treated with curative intent between 1983 and 2007 in the framework of the Rare Cancer Network. Results: Endometrial stromal sarcomas (ESS) were found in 44% and undifferentiated ESS (UES) in 49% of the cases. In 7% the grading was unclear. Of the total number of patients, 33 had Stage I, 4 Stage II, 20 Stage III, and 1 presented with Stage IVB disease. Adjuvant chemotherapy was administered to 12 patients, all with UES. External-beam radiotherapy (RT) was administered postoperatively to 48 women. The median follow-up was 41.4 months. The 5-year overall survival (OS) rate was 96.2% and 64.8% for ESS and UES, respectively, with a corresponding 5-year disease-free survival (DFS) rate of 49.4% and 43.4%, respectively. On multivariate analysis, adjuvant RT was an independent prognostic factor for OS (p = 0.007) and DFS (p = 0.013). Locoregional control, DFS, and OS were significantly associated with age (≤60 vs. >60 years), grade (ESS vs. UES), and International Federation of Gynecology and Obstetrics stage (I–II vs. III–IV). Positive lymph node staging had an impact on OS (p < 0.001). Conclusion: The prognosis of ESS differed from that of UES. Endometrial stromal sarcomas had an excellent 5-year OS, whereas the OS in UES was rather low. However, half of ESS patients had a relapse. For this reason, adjuvant treatment such as RT should be considered even in low-grade tumors. Multicenter randomized studies are still warranted to establish clear guidelines.

  3. Treatment outcome and prognostic factor of CO2 laser cordectomy for early glottic cancer

    Science.gov (United States)

    Chung, Phil-Sang; Lee, Sang Joon

    2012-02-01

    Objectives: Laser cordectomy is very popular nowadays and become one of the treatments of choice for early glottis carcinoma. Transoral laser microsurgery has many advantages comparing conventional open surgery or radiation therapy. In this study, we examined the oncologic results of laser cordectomy for early glottic cancer and analyzed the prognostic impact on the survival of the several tumor-related and treatment-related factors. Methods: Patients who were diagnosed as early glottic squamous cell carcinoma, treated by laser cordectomy with curative intent were analyzed. Patients with preivous radiation therapy were included. From June 1988 to March 2005, 202 patients from five hospitals were analyzed (174 T1, 28 T2). Results: Five-year overall survival and disease-free survival were 98.4% and 84.9%. Twenty two patients developed local recurrence. Total laryngectomy was done in 6 patients and laryngeal preservation rate was 97%. Recurrence was higher in the patients with anterior commissure involvement (9/39) than without anterior commissure involvement (13/163). Recurrence was higher in T1b (4/15) than T1a (13/159). Previous radiation was also highly related to the recurrence (7/20 vs 15/182). Twenty patients with local recurrence after radiation therapy were treated by salvage laser cordectomy. Of them, 7 patients developed local recurrence and 5 year disease-free survival was 57%. Complication was rare with one case of hemorrhage. Tracheotomy was not necessary in all patients. Conclusions: Laser cordectomy for early glottic carcinoma showed high survival, laryngeal preservation rate and low complication rate. The prognostic factors were anterior commissure involvement, both vocal fold involvement and previous radiotherapy.

  4. An analysis of prognostic factors in the uterine cervical cancer patients

    International Nuclear Information System (INIS)

    The aim of this study is to analysis of survival and recurrence rates of the uterine cervical carcinoma patients whom received the radiation therapy respectively. The prognostic factors, such as Papanicolaou (Pap) smear, carcinoembriogenic antigen (CEA) and squamous cell carcinoma (SCC) antigen has been studied. From January 1981 to December 1998, eight-hundred twenty-seven uterine cervical cancer patients were treated with radiation therapy. All of the patients were divided into two groups: the radiation therapy only (521 patients) group and the postoperative radiation therapy (326 patients) group. The age, treatment modality, clinical stage, histopathology, recurrence, follow-up Pap smears, CEA and see antigen were used as parameters for the evaluation. The prognostic factors such as survival and recurrence rates were performed with the Kaplan-Meier method and the Cox hazard model, respectively. Median fallow-up was 38.6 months. On the radiation therapy only group, 314 patients (60%) achieved complete response (CR), 47 patients (9%) showed local recurrence (LR), 78 patients (15%) developed distant metastasis (DM). On the postoperative radiation therapy group, showed 276 patients (85%) CR, 8 patients (2%) LR, 37 patients (11%) DM. The 5-year survival and recurrence rates was evaluated for all parameters. The statistically significant factors for the survival rate in univariate analysis were clinical stage (p=0.00001), treatment modality (p=0.0010), recurrence (p=0.0001), Pap smear (p=0.0329), CEA (p=0.0001) and SCC antigen (p=0.0001). This study indicated that after treatment, the follow-up studies of Pap smear, CEA and SCC antigen were significant parameter and prediction factors for the survival and recurrence of the uterine cervical carcinoma

  5. Prognostic Significance of Promoter DNA Hypermethylation of cysteine dioxygenase 1 (CDO1 Gene in Primary Breast Cancer.

    Directory of Open Access Journals (Sweden)

    Naoko Minatani

    Full Text Available Using pharmacological unmasking microarray, we identified promoter DNA methylation of cysteine dioxygenase 1 (CDO1 gene in human cancer. In this study, we assessed the clinicopathological significance of CDO1 methylation in primary breast cancer (BC with no prior chemotherapy. The CDO1 DNA methylation was quantified by TaqMan methylation specific PCR (Q-MSP in 7 BC cell lines and 172 primary BC patients with no prior chemotherapy. Promoter DNA of the CDO1 gene was hypermethylated in 6 BC cell lines except SK-BR3, and CDO1 gene expression was all silenced at mRNA level in the 7 BC cell lines. Quantification of CDO1 methylation was developed using Q-MSP, and assessed in primary BC. Among the clinicopathologic factors, CDO1 methylation level was not statistically significantly associated with any prognostic factors. The log-rank plot analysis elucidated that the higher methylation the tumors harbored, the poorer prognosis the patients exhibited. Using the median value of 58.0 as a cut-off one, disease specific survival in BC patients with CDO1 hypermethylation showed significantly poorer prognosis than those with hypomethylation (p = 0.004. Multivariate Cox proportional hazards model identified that CDO1 hypermethylation was prognostic factor as well as Ki-67 and hormone receptor status. The most intriguingly, CDO1 hypermethylation was of robust prognostic relevance in triple negative BC (p = 0.007. Promoter DNA methylation of CDO1 gene was robust prognostic indicator in primary BC patients with no prior chemotherapy. Prognostic relevance of the CDO1 promoter DNA methylation is worthy of being paid attention in triple negative BC cancer.

  6. Procalcitonin Improves the Glasgow Prognostic Score for Outcome Prediction in Emergency Patients with Cancer: A Cohort Study

    Directory of Open Access Journals (Sweden)

    Anna Christina Rast

    2015-01-01

    Full Text Available The Glasgow Prognostic Score (GPS is useful for predicting long-term mortality in cancer patients. Our aim was to validate the GPS in ED patients with different cancer-related urgency and investigate whether biomarkers would improve its accuracy. We followed consecutive medical patients presenting with a cancer-related medical urgency to a tertiary care hospital in Switzerland. Upon admission, we measured procalcitonin (PCT, white blood cell count, urea, 25-hydroxyvitamin D, corrected calcium, C-reactive protein, and albumin and calculated the GPS. Of 341 included patients (median age 68 years, 61% males, 81 (23.8% died within 30 days after admission. The GPS showed moderate prognostic accuracy (AUC 0.67 for mortality. Among the different biomarkers, PCT provided the highest prognostic accuracy (odds ratio 1.6 (95% confidence interval 1.3 to 1.9, P<0.001, AUC 0.69 and significantly improved the GPS to a combined AUC of 0.74 (P=0.007. Considering all investigated biomarkers, the AUC increased to 0.76 (P<0.001. The GPS performance was significantly improved by the addition of PCT and other biomarkers for risk stratification in ED cancer patients. The benefit of early risk stratification by the GPS in combination with biomarkers from different pathways should be investigated in further interventional trials.

  7. Meta-analysis of several gene lists for distinct types of cancer: A simple way to reveal common prognostic markers

    Directory of Open Access Journals (Sweden)

    Sun Xiao

    2007-04-01

    Full Text Available Abstract Background Although prognostic biomarkers specific for particular cancers have been discovered, microarray analysis of gene expression profiles, supported by integrative analysis algorithms, helps to identify common factors in molecular oncology. Similarities of Ordered Gene Lists (SOGL is a recently proposed approach to meta-analysis suitable for identifying features shared by two data sets. Here we extend the idea of SOGL to the detection of significant prognostic marker genes from microarrays of multiple data sets. Three data sets for leukemia and the other six for different solid tumors are used to demonstrate our method, using established statistical techniques. Results We describe a set of significantly similar ordered gene lists, representing outcome comparisons for distinct types of cancer. This kind of similarity could improve the diagnostic accuracies of individual studies when SOGL is incorporated into the support vector machine algorithm. In particular, we investigate the similarities among three ordered gene lists pertaining to mesothelioma survival, prostate recurrence and glioma survival. The similarity-driving genes are related to the outcomes of patients with lung cancer with a hazard ratio of 4.47 (p = 0.035. Many of these genes are involved in breakdown of EMC proteins regulating angiogenesis, and may be used for further research on prognostic markers and molecular targets of gene therapy for cancers. Conclusion The proposed method and its application show the potential of such meta-analyses in clinical studies of gene expression profiles.

  8. Exclusive brachytherapy for T1-T2 N0 cancer of the oral tongue: prognostic factors for local control

    International Nuclear Information System (INIS)

    INTRODUCTION: The files of a group of patients (pts) treated with brachytherapy alone for cancer of the oral tongue were reviewed to assess the prognostic role of T stage, volume of disease, total dose and dose-rate. PATIENTS METHODS AND RESULTS: From 1982 to 1994 46 pts (29 males, 17 females, age 38-84 years, median 63.1 years) were treated with 192 Ir brachytherapy, in 2 cases followed by prophylactic neck dissection for cancer of the oral tongue (T1N0: 19 pts; T2N0: 27 pts). Brachytherapy was performed with hairpins in the early years of the study (17 pts) and more recently with plastic tubes (29 pts), according to the Parts System. Dose ranged from 60-70 Gy with a dose-rate of 0.38-0.62 Gy/h (median 63.8 and 0.52 respectively). Volume of the disease was retrospectively assessed as the product of the three diameters of the lesion calculated for provisional dosimetry (range 0.25- 16 cc.). Median follow up is 72 mos (range: 14-153 mos). RESULTS: Overall local control was 82.6% ((38(46)) pts; T1: (18(19)), 94.7 %; T2: (22(27)), 81.5 %). Five of 8 pts who recurred were submitted to salvage surgery, and 3 of them are alive and free from disease at 34, 52 and 87 mos respectively. Recurrences appeared after 3-13 mos (median 5.5 mos) and were related to total dose ( 63 Gy (1(18)); 5.5 %) and to dose-rate ( 45 cGy/h (4(36)): 11.1 %). The volume of disease was not of prognostic significance since local control was 79.6 % ((6(28)) pts) in pts with a disease smaller than 3 cc. and 88.9 % in pts with large volume ((2(18)) pts). Seven (15.2 %) grade 3 complications (necrosis of the mandibular bone and- or of the soft tissues) were observed. Complication rate was higher in the high dose group (>63 Gy (4(18)) pts: 22.2 %) and was less affected by dose-rate (> 45 cGy/h (6(36)) pts: 16.6 %). No relationship between complications and volume was observed ( 3cc.: 16.6 %). All complications healed spontaneously. DISCUSSION AND CONCLUSION: For T1-T2 cancer of the oral tongue exclusive

  9. MicroRNA-1976 functions as a tumor suppressor and serves as a prognostic indicator in non-small cell lung cancer by directly targeting PLCE1.

    Science.gov (United States)

    Chen, Gang; Hu, Jing; Huang, Zhao; Yang, Lijing; Chen, Min

    2016-05-13

    Lung cancer remains a leading cause of cancer-associated mortality worldwide and non-small lung cancer (NSCLC) is responsible for over 80% of lung cancer-related deaths. Identifying novel molecular biomarker that can inhibit the progression of lung cancer will facilitate the development of new treatment strategies. Phospholipase C epsilon 1 (PLCE1) is a susceptibility gene in NSCLC. Nevertheless, the role of PLCE1 in NSCLC tumorigenesis has not been elucidated. Herein, we demonstrated that miR-1976 is a tumor-suppressor miRNA in NSCLC progression. We found that expression of miR-1976 was decreased obviously in NSCLC tissues. Down-regulation of miR-1976 was associated with TNM stage and postoperative survival. Overexpression of miR-1976 inhibited the growth and metastasis of NSCLC cells. The PLCE1 was a direct target of miR-1976 and promoted the growth and metastasis of NSCLC cells. Further study showed that PLCE1 could reverse the inhibitory effect of miR-1976 on growth and metastasis of NSCLC cells. Taken together, our data highlight the pivotal role of miR-1976 in the progression of NSCLC. Thus, miR-1976 may be a potential prognostic marker and of treatment relevance for NSCLC progression intervention. PMID:27063799

  10. Anti-epidermal or anti-vascular endothelial growth factor as first-line metastatic colorectal cancer in modified Glasgow prognostic score 2' patients

    OpenAIRE

    Dréanic, Johann; Dhooge, Marion; Barret, Maximilien; Brezault, Catherine; Mir, Olivier; Chaussade, Stanislas; Coriat, Romain

    2015-01-01

    Background In metastatic colorectal cancer, the modified Glasgow prognostic score (mGPS) has been approved as an independent prognostic indicator of survival. No data existed on poor prognosis patients treated with molecular-targeted agents. Methods From January 2007 to February 2012, patients with metastatic colorectal cancer and poor predictive survival score (mGPS = 2), treated with 5-fluorouracil-based chemotherapy in addition to an anti-epidermal growth factor receptor (EGFR) or anti-vas...

  11. Status of cellular immunity lacks prognostic significance in vulvar squamous carcinoma

    NARCIS (Netherlands)

    de Jong, R.A.; Toppen, N. L.; ten Hoor, K. A.; Boezen, H. M.; Kema, I. P.; Hollema, H.; Nijman, H. W.

    2012-01-01

    Objective. It is generally recognized that the immune system has an important role in regulating cancer development. Evidence indicating a prognostic role of the immune system in vulvar carcinoma is scarce. This study investigated the presence and prognostic significance of several aspects of the im

  12. Prognostic value of 18-fluorodeoxyglucose positron emission tomography-computed tomography in resectable colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Jang Eun Lee; Sang Woo Kim; Jin Su Kim; Kyu Yong Choi; Won Kyung Kang; Seong Taek Oh; Ie Ryung Yoo

    2012-01-01

    AIM:To assess the prognostic value of preoperative 18 fluorodeoxyglucose positron emission tomography (FDG-PET)/computed tomography (CT) in patients with resectable colorectal cancer.METHODS:One hundred sixty-three patients with resectable colorectal cancer who underwent FDG-PET/CT before surgery were included.Patient data including pathologic stage at presentation,histology,treatment,disease-free survival and the maximum standardized uptake value (SUVmax) of the primary tumor on FDGPET/CT were retrospectively analyzed.Median follow up duration was 756 (range,419-1355).The primary end point was disease-free survival.RESULTS:Twenty-five of 163 patients (15.3%) had recurrences.The median SUVmax values of the recurrence and no-recurrence groups were 8.9 (range,5-24) and 8.2 (range,0-23,P =0.998).Receiver operating characteristic (ROC) curve analysis showed no significant association between SUVmax and recurrence (area under the curve =0.5,P =0.998,95%CI:0.389-0.611).Because a statistically significant value was not found,SUVmax was dichotomized at its median of 8.6.The disease-free survival curve was analyzed using the median SUVmax (8.6) as the cut off.Univariate and multivariate analysis did not provide evidence that disease-free survival rates for the subgroups defined by the median SUVmax were significantly different (P =0.52,P =0.25).CONCLUSION:Our study suggests that the high FDG uptake of primary mass in resectable colorectal cancer doesn't have a significant relationship with tumor recurrence and disease-free survival.

  13. Expression analysis and prognostic significance of the SRA1 gene, in ovarian cancer

    International Nuclear Information System (INIS)

    The SR-related-CTD-associated-factors (SCAFs) have the ability to interact with the C-terminal domain of the RNA polymerase II, linking this way transcription to splicing. SRA1 (SR-A1) gene, encoding for a human high-molecular weight SCAF protein, is located on chromosome 19, between the IRF3 and the R-RAS oncogene and it has been demonstrated from members of our group that SRA1 is constitutively expressed in most of the human tissues, while it is overexpressed in a subset of ovarian tumors. In this study, we examine the expression of SRA1 gene in 111 ovarian malignant tissues and in the human ovarian carcinoma cell lines OVCAR-3, TOV21-G, and ES-2, using a semi-quantitative RT-PCR method. SRA1 gene was overexpressed in 61/111 (55%) of ovarian carcinomas. This higher expression was positively associated to the size of the tumor (p < 0.001), the grade and the stage of the disease (p = 0.003 and p = 0.006, respectively), and the debulking success (p < 0.001). Kaplan-Meier survival analysis revealed that lower SRA1 expression increases the probability of both the longer overall and the progression free survival of the patients. Multivariate Cox regression analysis revealed that SRA1 may be used as an independent prognostic biomarker in ovarian cancer. Our results suggest that SRA1 is associated with cancer progression and may possibly be characterized as a new marker of unfavorable prognosis for ovarian cancer

  14. Concurrent cisplatin and radiotherapy for inoperable bladder cancer: long term results and prognostic predictors of local control and survival

    International Nuclear Information System (INIS)

    Therapeutic strategies for muscle invasive bladder cancer are currently evolving. A recent European randomized study has shown that neo-adjuvant chemotherapy does not improve the chance of cure or of conservative treatment. Concurrent chemotherapy and radiotherapy would provide better results but these is a need to identify by prognostic factors patients who may benefit from such a conservative strategy. Concurrent cisplatin and radiation therapy is a potentially locally curative treatment for 43 % of patients with muscle-invasive bladder cancer not candidates for radical surgery. Clinical T-stage and hydronephrosis have a significant and independent prognostic value on local control but appears not discriminant enough to select patients for conservative treatment. (authors)

  15. Prognostic Value of Cancer Stem Cells Markers in Triple-Negative Breast Cancer

    OpenAIRE

    Collina, Francesca; Di Bonito, Maurizio; Li Bergolis, Valeria; De Laurentiis, Michelino; Vitagliano, Carlo; Cerrone, Margherita; Nuzzo, Francesco; Cantile, Monica; Botti, Gerardo

    2015-01-01

    Triple-negative breast cancer (TNBC) has a significant clinical relevance of being associated with a shorter median time to relapse and death and does not respond to endocrine therapy or other available targeted agents. Increased aggressiveness of this tumor, as well as resistance to standard drug therapies, may be associated with the presence of stem cell populations within the tumor. Several stemness markers have been described for the various histological subtypes of breast cancer, such as...

  16. Prognostic Role of Multiple Cardiac Biomarkers in Newly Diagnosed Acute Coronary Syndrome Patients.

    Science.gov (United States)

    Rahman, M M; Alam, M M; Jahan, N A; Shila, J S; Arslam, M I

    2016-04-01

    Acute coronary syndrome includes unstable angina and myocardial infarction with or without ST-segment elevation, is life-threatening disorders that remain a source of high morbidity and mortality despite advances in treatment. The aim of the study was to evaluate the prognostic role of serum cTnI, CK-MB, hsCRP, MPO and BNP in newly diagnosed acute coronary syndrome patients. This cohort study was carried out in the Department of Biochemistry, Bangabandhu Sheikh Mujib Medical University in cooperation with the Department of Cardiology, BSMMU and NICVD during the period of March 2013 to February 2014. A total 100 newly diagnosed acute coronary syndrome patients were purposively enrolled in this study within 24 hours of attacked, among them 30 were NSTEMI, 65 were STEMI and 5 were unstable angina. Serum cTnI, CK-MB, hsCRP, MPO and BNP concentrations were measured at enrollment and grouping of the study subjects were done on the basis of their empirical cut off values into two groups. In cTnI: Group I (n=20) having cTnI ratio analysis showed significantly worse outcome in Group II acute coronary syndrome patients in comparison to Group I. In case of cTnI RR - 1.85 at 95% CI 1.19-2.88, in case of CK-MB RR- 1.88 at 95% CI 1.21-2.92, in case of hsCRP RR- 2.05 at 95% CI 1.30-3.25, in case of MPO RR- 2.59, at 95% CI 1.49-4.49, and in case of BNP RR- 3.47 at 95% CI 2.5-5.36. It was concluded from this study that base line serum cTnI, CK-MB, hsCRP, MPO, and BNP can be used clinically as prognostic biomarkers of acute coronary syndrome. PMID:27277367

  17. Sox17 promoter methylation in plasma DNA is associated with poor survival and can be used as a prognostic factor in breast cancer.

    Science.gov (United States)

    Fu, Deyuan; Ren, Chuanli; Tan, Haosheng;