Premium
Characterization of the molecular differences between ovarian endometrioid carcinoma and ovarian serous carcinoma
Author(s) -
Madore Jason,
Ren Fengge,
FilaliMouhim Ali,
Sanchez Lilia,
Köbel Martin,
Tonin Patricia N,
Huntsman David,
Provencher Diane M,
MesMasson AnneMarie
Publication year - 2010
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.2659
Subject(s) - pten , serous fluid , serous carcinoma , immunohistochemistry , pathology , biology , carcinoma , cancer research , clear cell , ovarian carcinoma , cancer , ovarian cancer , medicine , pi3k/akt/mtor pathway , signal transduction , biochemistry , genetics
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 β‐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, β‐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 . Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.