scholarly journals Emerging Role of Inhibin as a Biomarker for Ovarian Cancer

2005 ◽  
Vol 1 (1) ◽  
pp. 51-57 ◽  
Author(s):  
David M Robertson ◽  
Martin K Oehler

Ovarian cancer is the most lethal gynecological malignancy as it is diagnosed at a late clinical stage in more than 80% of patients. The development of diagnostic tests that can detect all types of ovarian cancers with high specificity and sensitivity, and at an early stage would improve survival rates. Serum inhibin is an ovarian hormone involved in the regulation of fertility, decreasing to undetectable levels after menopause. Certain ovarian malignancies, such as mucinous carcinomas and granulosa cell tumors, continue to produce inhibin, which is detectable in serum. A test for serum inhibin has been developed which is able to diagnose granulosa cell tumors and mucinous carcinomas with high accuracy. When the inhibin assay is used in conjunction with the CA125 test, which detects epithelial ovarian carcinomas, the two tests detect the majority of ovarian cancers with high sensitivity (95%) and specificity (95%). This article discusses the application of the inhibin test in ovarian cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e16527-e16527
Author(s):  
Sakina Sekkate ◽  
Mouna Kairouani ◽  
Badr Serji ◽  
Brahim el Ghissassi ◽  
Hind Mrabti ◽  
...  

e16527 Background: The granulosa cell tumors are malignancies with a relatively favorable prognosis. They are characterized by prolonged natural history and tendency to late recurrences. The aim of this study is to investigate the epidemiological and pathological characteristics of granulosa cell tumors, and the prognosis factor for recurrences in the national institute of oncology in Rabat in Morocco. Methods: The clinical data of patients with adult granulosa cell tumors of the ovary treated from January 2003 to december 2010 was investigated retrospectively. Data of age, clinical manifestation, imaging, diagnosis, treatment and follow up of the patients were reviewed and analyzed. Histology was obtained in postoperative for all patients. Results: Twenty-seven cases were retrieved. The median age was 53 years. The most common clinical manifestations at diagnosis were: abdominal pain, vaginal bleeding, abdominal distension and hormonal manifestations. The mean tumor size was 14 cm. The majority of patients had stage I (62,96%, n = 17), while (18,51%, n = 5) had stage III, (7,4%, n = 2) had stage IV, and (11,11%, n = 3) of patients had unknown stage.8 patients received adjuvant chemotherapy (4 : bleomycin etoposide, cisplatin (BEP); 1: bleomycin vepeside cisplatin (BVP); 1: endoxan cisplatin; 1: paclitaxel cisplatin; 1: tamoxifene), and 2 patients received chemotherapy for metastatic disease.For a median follow up of 63,44 months, 5 (18,51%) of patients relapsed. The median time to relapse was 41,8 months, (range : 18-62 months).The overall 5-year survival and 9-year survival rates for all stages were 91.3% and 77.3%, respectively. Following univariate Cox regression modeling, the survival depends on stage, it’s better in localized stages (p = 0,05). Conclusions: Granulosa cell tumor of the ovary is an uncommon neoplasm. The adult form progresses slowly and often is diagnosed in an early stage of disease. Surgery is indicated. A prolonged post therapeutic follow-up is necessary because of the risk of recurrences, late and exceptional for the adult form.


2011 ◽  
Vol 2011 ◽  
pp. 1-17 ◽  
Author(s):  
Brandon J. D. Rein ◽  
Sajal Gupta ◽  
Rima Dada ◽  
Joelle Safi ◽  
Chad Michener ◽  
...  

This paper reviews current screening techniques as well as novel biomarkers and their potential role in early detection of ovarian cancer. Ovarian cancer is one of the most common reproductive cancers and has the highest mortality rate amongst gynecologic cancers. Because most ovarian cancer diagnoses occur in the late stages of the disease, five-year survival rates fall below 20%. To improve survival rates and to lower mortality rates for ovarian cancer, improved detection at early stages of the disease is needed. Current screening approaches include tumor markers, ultrasound, or a combination. Efforts are underway to discover new biomarkers of ovarian cancer in order to surmount the obstacles in early-stage diagnosis. Among serum protein markers, HE4 and mesothelin can augment CA125 detection providing higher sensitivity and specificity due to the presence of these proteins in early-stage ovarian cancer. Detection testing that includes methylation of the MCJ gene and increased expression of vascular endothelial growth factor is correlated to poor prognosis and may predict patient survival outcome. Detection testing of biomarkers with long-term stability and combination panels of markers, will likely lead to effective screening strategies with high specificity and sensitivity for early detection of ovarian cancer.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16571-e16571
Author(s):  
T. Sawasaki ◽  
Y. Katsube

e16571 Background: The purpose of this study was to examine the expression of splice variants of the Ep-CAM gene in normal ovarian epithelial tissue and ovarian carcinoma and further to associate the expression of Ep-CAM with clinicopathologic characteristics if such an association exists. Methods: Ep-CAM expression was examined by semiquantitative PCR in 122 ovarian tumors (92 adenocarcinomas, 10 low malignant potential (LMP) tumors, and 10 adenomas) and 10 normal ovaries. Results: In carcinomas as well as LMP tumors and adenomas, Ep-CAM mRNA expression was significantly elevated compared to that in normal ovary samples. Ep-CAM mRNA expression level in carcinomas was significantly elevated compared to that in adenomas and Ep-CAM mRNA expression level in advanced clinical stage diseases was significantly higher than that in early stage diseases in ovarian carcinomas. With regard to histological type, Ep-CAM mRNA expression level in mucinous adenocarcinomas was significantly higher than those in the other tissue subtypes. Conclusions: These features imply that Ep-CAM expression may play an important role in ovarian cancer development and progression, and this may be useful as a diagnostic marker. No significant financial relationships to disclose.


2019 ◽  
Vol 65 (1) ◽  
pp. 56-62
Author(s):  
Alisa Villert ◽  
Larisa Kolomiets ◽  
Natalya Yunusova ◽  
Yevgeniya Fesik

High-grade ovarian carcinoma is a histopathological diagnosis, however, at the molecular level, ovarian cancer represents a heterogeneous group of diseases. Studies aimed at identifying molecular genetic subtypes of ovarian cancer are conducted in order to find the answer to the question: can different molecular subgroups influence the choice of treatment? One of the achievements in this trend is the recognition of the dualistic model that categorizes various types of ovarian cancer into two groups designated high-grade (HG) and low-grade (LG) tumors. However, the tumor genome sequencing data suggest the existence of 6 ovarian carcinoma subtypes, including two LG and four HG subtypes. Subtype C1 exhibits a high stromal response and the lowest survival. Subtypes C2 and C4 demonstrate higher number of intratumoral CD3 + cells, lower stromal gene expression and better survival than sybtype C1. Subtype C5 (mesenchymal) is characterized by mesenchymal cells, over-expression of N-cadherin and P-cadherin, low expression of differentiation markers, and lower survival rates than C2 and C4. The use of a consensus algorithm to determine the subtype allows identification of only a minority of ovarian carcinomas (approximately 25%) therefore, the practical importance of this classification requires additional research. There is evidence that it makes sense to randomize tumors into groups with altered expression of angiogenic genes and groups with overexpression of the immune response genes, as in the angiogenic group there is a comparative superiority in terms of survival. The administration of bevacizumab in the angiogenic group improves survival, while the administration of bevacizumab in the immune group even worsens the outcome. Molecular subtypes with worse survival rates (proliferative and mesenchymal) also benefit most from bevacizumab treatment. This review focuses on some of the advances in understanding molecular, cellular, and genetic changes in ovarian carcinomas with the results achieved so far regarding the formulation of molecular subtypes of ovarian cancer, however further studies are needed.


2003 ◽  
Vol 19 (1) ◽  
pp. 11-17 ◽  
Author(s):  
Cristina Rodríguez-Burford ◽  
David C. Chhieng ◽  
Cecil R. Stockard ◽  
Marc J. Kleinberg ◽  
Mack N. Barnes ◽  
...  

Ovarian cancer has a high mortality rate largely due to the limited number of ovarian carcinomas detected at an early stage. Understanding the molecular changes occurring during the progression of ovarian carcinoma would aid in the development of therapies that may inhibit or target metastasis. Primary and metastatic lesions from 54 and 40 patients with advanced ovarian carcinoma, respectively (including matched primary and metastatic lesions from 30 patients) were evaluated for nuclear accumulation of p53 (clone BP53-12-1) and cytoplasmic and membranous immunostaining of p185 erbB-2 (clone 3B5) by immunohistochemistry. No differences in the immunostaining of p53 and p185erbB-2 (cytoplasm or membrane) were observed between primary and metastatic lesions of the matched cases. Similarly, no differences in the proportion of positive cases of p53 between primary and metastatic lesions of the matched cases was observed. Thus, novel therapies that target p53 or p185erbB-2 can utilize specimens from either primary or metastatic lesions to characterize these targets prior to therapy. Spearman correlations between p53 and p185erbB-2 (cytoplasm or membrane) immunohistochemistry scores were insignificant for the matched cases, all primary lesions, and all metastatic lesions. Also, no significant associations occurred between nuclear accumulation of p53 (positive versus negative) and phenotypic expression of p185erbB-2 (cytoplasm or membrane) immunostaining scores for the matched cases, all primary lesions, and all metastatic lesions. Thus, the nuclear accumulation of p53 and immunostaining of p185erbB-2 in the cytoplasm or on the cellular membranes are independent.


2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Zihui Xu ◽  
Hui Wang ◽  
Ling Gao ◽  
Hongfeng Zhang ◽  
Xiangyang Wang

Background. Colorectal cancer (CRC) is one of the most common cancers worldwide. Surgical operation is routinely applied to patients with CRC. An important part of postoperative care for patients is to assess the prognosis of patients, especially those with early-stage cancers. However, effective biomarkers for CRC prognosis remain inadequate. The purpose of this study was to assess the prognostic potential of Yes-associated protein (YAP) and carcinoembryonic antigen (CEA) in early-stage CRC. Methods. A total of 116 matched pairs of CRC tissues and adjacent normal mucosae as well as 73 cases of metastatic lymph nodes were analyzed. Results. The results show that CRC tissues exhibited higher YAP expression compared with the adjacent normal mucosae. Immunohistochemical analysis shows that YAP expression in the CRC or lymphatic metastatic tissues was clearly higher than that in normal mucosae (P<0.01), whereas that in CRC tissues with lymphatic metastasis was higher than that in tissues without lymphatic metastasis (P<0.05). YAP expression is associated with serosal invasion, lymphatic metastasis, lymph node ratio, remote metastasis, Dukes stage, and CEA levels (P<0.05). YAP and CEA are independent predictors of the survival of CRC patients (P<0.05 and P<0.01). YAP predicted CRC prognosis primarily for patients with late-clinical-stage CRC (P=0.002), but not for patients with early-clinical-stage CRC (P=0.083). However, patients with high YAP and high CEA levels exhibited lower overall survival rates than those with low YAP expression in early-clinical-stage CRC (P<0.001). Conclusion. High YAP levels in the cancer tissues combined with high plasma CEA levels are potential biomarkers for predicting CRC prognosis in the early clinical stage.


BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Hanna Engqvist ◽  
Toshima Z. Parris ◽  
Anikó Kovács ◽  
Szilárd Nemes ◽  
Elisabeth Werner Rönnerman ◽  
...  

Abstract Background Ovarian cancer is the main cause of gynecological cancer-associated death. However, 5-year survival rates differ dramatically between the five main ovarian carcinoma histotypes. Therefore, we need to have a better understanding of the mechanisms that promote histotype-specific ovarian carcinogenesis and identify novel prognostic biomarkers. Methods Here, we evaluated the prognostic role of 29 genes for early-stage (I and II) ovarian carcinomas (n = 206) using immunohistochemistry (IHC). Results We provide evidence of aberrant protein expression patterns for Collagen type III alpha 1 chain (COL3A1), G protein-coupled receptor 158 (GPR158) and PITH domain containing 1 (PITHD1). Kaplan-Meier survival analysis revealed that COL3A1 expression was associated with shorter overall survival in the four major histotypes of epithelial ovarian carcinoma patients (P value = 0.026, HR = 2.99 (95% CI 1.089–8.19)). Furthermore, GPR158 and PITHD1 were shown to be histotype-specific prognostic biomarkers, with elevated GPR158 expression patterns in mucinous ovarian carcinoma patients with unfavorable overall survival (P value = 0.00043, HR = 6.13 (95% CI 1.98–18.98)), and an association with lower PITHD1 protein expression and unfavorable overall and disease-specific survival in clear-cell ovarian carcinoma patients (P value = 0.012, HR = 0.22 (95% CI 0.058–0.80); P value = 0.003, HR = 0.17 (95% CI 0.043–0.64)). Conclusions The novel biomarkers identified here may improve prognostication at the time of diagnosis and may assist in the development of future individualized therapeutic strategies for ovarian carcinoma patients.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15548-e15548
Author(s):  
Ritvi K Bagadia ◽  
Vishal Uchila Shishir Rao ◽  
Ajay Balakrishnan ◽  
Abhijith George ◽  
Prashant Kumar

e15548 Background: Around 90% of cancer-related mortalities are caused by tumor metastasis. CTC clusters, which constitute an intermediate stage of metastasis, have not been studied extensively in head & neck cancers. The mortality rate of oral cancers remains alarmingly high, despite multimodality treatment. The aim of the study is to identify the presence of CTC clusters in patients with Oral Squamous Cell Carcinoma (OSCC) and to correlate their presence with clinical and pathological factors. Methods: Fifty patients diagnosed with histologically proven OSCC, treatment naïve, and underwent surgery at HCG Cancer Centre, Bangalore, were consented and enrolled in the study. An IRB-approved protocol allowed for the collection of 10 ml of blood from central (jugular) and peripheral veins intra-operatively, prior to tumor removal. The culturing of CTC clusters was done using ellipsoidal microwell plates maintained at hypoxic conditions, at the Institute of Bioinformatics, Bangalore. After fourteen days of culturing, the cells were fixed and stained for DAPI, Pan-CK and CD45. The CTC clusters were classified into Loose, Tight and very Tight based on the median gray values obtained from DAPI staining on ImageJ software. Clinical data was collected from patient records and subjected to analysis using Descriptive statistics. Results: From the 50 patients included in the study, 22 (44%) patients exhibited tight clusters in central blood, while only 13 (26%) patients exhibited tight clusters in peripheral blood. A higher clinical stage was observed in a greater percentage of patients with tight clusters in central blood (early: 45.5% versus late: 54.5%), but the same findings could not be inferred with pathological staging (early stage: 59.1% versus late stage: 40.1%). No significant correlation with adverse pathological features was noted. Conclusions: This observational study provides an insight into the varying biological behaviours of similarly grouped cancers, which is based on the standard TNM staging. The study forms the basis for the hypothesis of tight clusters in the central and peripheral circulation, correlating with loco-regional and distant metastasis respectively, thus leading to poorer disease-free and overall survival rates.


2004 ◽  
Vol 22 (4) ◽  
pp. 678-685 ◽  
Author(s):  
Andreas Scorilas ◽  
Carla A. Borgoño ◽  
Nadia Harbeck ◽  
Julia Dorn ◽  
Barbara Schmalfeldt ◽  
...  

PurposeHuman kallikrein 13 (hK13; encoded by the KLK13 gene) is a secreted serine protease expressed in endocrine tissues, including the prostate, testis, breast, and ovary. We have previously reported steroid hormone regulation of the KLK13 gene and its clinical value as a marker of favorable prognosis in breast cancer at the mRNA level. We hypothesized that hK13 may represent a potential biomarker for ovarian carcinomas.Patients and MethodsUsing a newly developed enzyme-linked immunosorbent assay (ELISA), hK13 levels were quantified in 131 ovarian tumor extracts and correlated with various clinicopathological variables and outcome (progression-free survival [PFS], overall survival [OS]), over a median follow-up period of 42 months.ResultshK13 concentration in ovarian tumor cytosols ranged from 0 to 18.4 ng/mg of total protein. An optimal cutoff value of 0.13 ng/mg (67thpercentile) was selected, based on the ability of hK13 values to predict the PFS of the study population, to categorize tumors as hK13-positive or negative. Women with hK13-positive tumors most often had early stage (stage I/II) disease, no residual tumor after surgery and optimal debulking success (P < .05). Univariate and multivariate Cox regression analyses revealed that patients with hK13-positive tumors had a significantly longer PFS and OS than hK13-negative patients (P < .05). Kaplan-Meier survival curves further confirmed a reduced risk of relapse and death in women with hK13-positive tumors (P = .007 and P = .002, respectively).ConclusionThese results indicate that hK13 is an independent marker of favorable prognosis in ovarian cancer.


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