Gene Expression Analysis Identifies Two Groups of Ovarian High-Grade Serous Carcinomas with Different Prognosis.
Inigo Espinosa, Lluis Catasus, Belen Canet, Emanuela D'Angelo, Fina Munoz, Jaime Prat. Hospital de la Santa Creu i Sant Pau. Institute of Biomedical Research (IIB Sant Pau), Autonomous University of Barcelona, Barcelona, Spain
Background: Gene expression profiling is an important tool to evaluate genetic heterogeneity in carcinomas and is useful for developing expression-based classifications of many cancers as well as markers of disease outcome.
Design: We have examined by Taqman Low-Density Array (TLDA) the expression profiling of 22 genes involved in the PI3K-AKT pathway in 26 high-grade ovarian carcinomas (19 serous and 7 clear cell carcinomas). Gene expression pattern was analyzed by hierarchical clustering analysis and results were correlated with clinicopathological features. To validate the gene expression data, we selected two markers (caspase-3 and XIAP) and investigated their protein expression in 18 high-grade serous carcinomas.
Results: Unsupervised hierarchical clustering divided high-grade ovarian carcinomas into three groups. All clear cell carcinomas clustered into one group. In contrast, high-grade serous carcinomas were segregated into two clusters with different prognosis (P=0.05). High expression of CASP3, XIAP, NFKB1, FAS, and GSK3B mRNAs identified high-grade serous carcinomas with better prognosis. These cluster groups were of prognostic significance independent of age, tumor size, and tumor stage in multivariate analysis (P=0.008). Immunoreaction for caspase-3 was concordant with the results obtained by gene expression analysis (Spearman r=0.762, P=0.000). Furthermore, co-expression of caspase-3 and XIAP identified cases with different prognosis (P=0.03).
Conclusions: Our results suggest that there are different subtypes of high-grade serous carcinomas with different biological behavior.
Category: Gynecologic & Obstetrics
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 96, Tuesday Afternoon