Multiple Gene Expression Analysis by Taqman Low-Density Array in High-Grade Endometrial Adenocarcinomas
Ll Catasus, A Gallardo, M Cuatrecasas, J Prat. Hospital de la Santa Creu i Sant Pau. Autonomous University of Barcelona, Barcelona, Spain
Background: Gene expression profiling is an important tool to evaluate genetic heterogeneity in carcinomas and to identify tumor-specific genes.
Design: mRNA level expression was analyzed in 22 endometrial carcinomas (9 EEC, 8 NEEC, and 5 mixed carcinomas EEC-NEEC). Gene expression analyses was performed at mRNA level by Taqman low-density array (TLDA). We were configured the TLDA card with 22 genes involved in PIK3/AKT signaling pathway and apoptosis, and two housekeeping genes, GAPDH and ABL-1. PCR amplification was performed using an Applied Biosystems 7900HT PCR system. Hierarchical cluster analysis was performed with Cluster program and visualized with the TreeView program from Stanford (http://rana.lbl.gov/EisenSoftware.html). The results of the mRNA expression were correlated with MI, PTEN, PIK3CA, p53, K-RAS, CTNNB1 and with clinical, pathologic parameters, and patients' follow-up.
Results: Hierarchical cluster analysis revealed two subgroups of high grade endometrial carcinomas: one group of 15 tumors showed overexpression of genes involved in PIK3/AKT signaling pathway (AKT1, AKT2, FAK, PAK1, GSK3B, and mTOR), and apoptosis (XIAP, p53, NFKB, and caspase 3). The other group of 7 tumors showed lower expression of these markers. Interestingly, in the first group there was high frequency of exon 20 PIK3CA or PTEN mutations (10/15) whereas the second group had p53 alterations (6/7). Coexpression of AKT1 and AKT2 and correlation with exon 20 PIK3CA mutations were found. There was no correlation with histological type or clinicopathological features. However, all tumors were high-grade carcinomas.
Conclusions: Hierarchical cluster association in multiple gene expression analysis for the PIK3/AKT and apoptosis showed two groups of high-grade endometrial carcinomas: one correlated with exon 20 PIK3CA or PTEN mutations and the other with p53 alterations.
Wednesday, March 11, 2009 1:00 PM
Poster Session VI # 152, Wednesday Afternoon