Characterization of the molecular differences between ovarian endometrioid carcinoma and ovarian serous carcinoma

Abstract

The histopathological diagnosis of high-grade endometrioid and serous carcinoma of the ovary is poorly reproducible under the current morphology based classification system, especially for anaplastic, high-grade tumours. The transcription factor Wilms' tumour-1 (WT1) is differentially expressed among the gynaecological epithelia from which epithelial ovarian cancers (EOCs) are believed to originate. In EOCs, WT1 protein is observed in the majority of serous carcinomas and in up to 30% of endometrioid carcinomas. It is unclear whether the latter is a reflection of the actual incidence of WT1 protein expression in endometrioid carcinomas, or whether a significant number of high-grade serous carcinomas have been misclassified as endometrioid carcinoma. Several genetic aberrations are reported to occur in EOCs. These include mutation of the TP53 gene, aberrant activation of beta-catenin signalling and loss of PTEN protein expression, among others. It is unclear whether these aberrations are histotype-specific. The aim of this study was to better define the molecular characteristics of serous and endometrioid carcinomas in an attempt to address the problems with the current histopathological classification methods. Gene expression profiles were analysed to identify reproducible gene expression phenotypes for endometrioid and serous carcinomas. Tissue microarrays (TMA) were used to assess the incidence of TP53, beta-catenin and PTEN aberrations in order to correlate their occurrence with WT1 as an immunohistochemistry based biomarker of serous histotype. It was found that nuclear WT1 protein expression can identify misclassified high-grade endometrioid carcinomas and these tumours should be reassigned to serous histotype. Although low-grade endometrioid carcinomas rarely progress to high-grade carcinomas, a combined WT1-negative, TP53-positive immunophenotype may identify an uncommon high-grade subtype of ovarian endometrioid carcinoma. GEO database: array data accession number GSE6008.