Gene expression analysis identifies two groups of ovarian high-grade serous carcinomas with different prognosis

Inigo Espinosa, Lluis Catasus, Belén Canet, Emanuela D'Angelo, Josefina Mũoz, Jaime Prat

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21 Citations (Scopus)

Abstract

Gene expression profiling is an important tool to evaluate genetic heterogeneity in carcinomas and is useful to develop expression-based classifications for many types of cancer, as well as markers of disease outcome. In this study, we have investigated the expression profile of 22 genes involved in the PI3K-AKT pathway in 26 high-grade ovarian carcinomas (19 serous and 7 clear cell carcinomas). Unsupervised hierarchical clustering divided high-grade ovarian carcinomas into three groups. Although all clear cell carcinomas clustered in one group, high-grade serous carcinomas were segregated into two separate groups with different prognosis (P=0.05). High expression of CASP3, XIAP (X-linked inhibitor of apoptosis), NFKB1, FAS, and GSK3B mRNAs identified high-grade serous carcinomas with better prognosis. In multivariate analysis, these cluster groups were of prognostic significance independent of age, tumor size, and tumor stage (P=0.008). To validate the mRNA expression data, we studied the immunohistochemical expression of caspase-3 and XIAP on a tissue microarray. Immunoreaction for caspase-3 was concordant with the results obtained by mRNA expression analysis (Spearman r=0.762, P=0.000). Caspase-3 was exclusively expressed by the macrophages. Furthermore, co-expression of caspase-3 and XIAP identified high-grade serous carcinomas with different prognosis (P=0.03). Our results suggest that there are different biological subtypes of high-grade serous carcinomas. © 2011 USCAP, Inc. All rights reserved.
Original languageEnglish
Pages (from-to)846-854
JournalModern Pathology
Volume24
Issue number6
DOIs
Publication statusPublished - 1 Jun 2011

Keywords

  • clustering analysis
  • high-grade serous carcinomas
  • outcome
  • PI3K-AKT pathway

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