Immunohistochemical molecular markers in type I and type II ovarian carcinomas and their correlation with survival

Abstract

This study aims to evaluate the expression of immunohistochemical markers in carcinomas and borderline ovarian tumors. Ovarian cancer is the leading cause of death among gynecological malignancies, even though ranking only fifth in prevalence of gynecological tumors. Malignant epithelial tumors represent approximately ninety per cent of ovarian tumors. Each subtype is associated with a multiplicity of genetic factors and specific molecular events during oncogenesis. Even though there is a histological heterogeneity, in most cases, these tumors are treated similarly, leading to different responses to treatment and prognosis. Recent evidence suggests that a new classification model that considers two groups of malignant epithelial tumors should be considered: type I carcinomas including low grade serous carcinomas, primarymucinous ovarian carcinomas, endometroid carcinomas and clear cell carcinomas, usually restricted to the ovary at diagnosis and with indolent behavior; and Type II tumors, composed of high-grade serous carcinomas and undifferentiated carcinomas, usually with high expression of P53, which are aggressive and often detected in advanced stages. The genetic changes can be identified indirectly through immunohistochemical methods that identify prognostic markers and aid in diagnosis. The specific objective of this study is to evaluate the immunohistochemical expression of p53, Ki67, WT1, beta-catenin and BRCA1/2 in type I and II primary invasive epithelial ovarian tumors, according to stage and disease-free interval and overall survival. Subjects and methods: This is an observational retrospective cohort study. Paraffin blocks of 250 women with primary malignant epithelial ovarian tumors will be selected from medical records of patients who attended medical consultations at the Women´s Hospital of the State University of Campinas (CAISM) between 1993-2013. Patients should not have received neoadjuvant chemotherapy and/or radiotherapy. Biomarkers expression will be ascertained using immunohistochemistry after tissue microarray construction (TMA). Marker expression will be compared in type I and type II tumors, controlled for disease stage and disease-free interval and overall survival. Sample size was estimated from the difference in the overall survival of patients with ovarian carcinoma, considering Ki67 as a prognostic factor, classified as expressed in less than 10% and greater than 10%. From this information and adopting an alpha of 5% and 90% power, the estimated sample size is 250 patients.