Gene expression profiling of tamoxifen-associated uterine cancers: evidence for two molecular classes of endometrial carcinoma

Objective. Endometrial cancers associated with tamoxifen exposure potentially represent a unique resource for investigating the molecular mechanisms of estrogen-induced tumorigenesis. The purpose of this study was to test the hypothesis that tamoxifen-associated endometrial carcinomas have a distinct gene expression profile compared to matched cases not associated with this exposure. Methods. Microarray-based expression profiling was performed on a series of tamoxifen-associated (N = 10) and matched sporadic cases (N = 29) of endometrial carcinoma. Results. Supervised class comparison revealed no statistically significant difference between the two groups (P = 0.48). However, unsupervised hierarchical Clustering of the entire sample of tumors revealed two groups with extremely diverse molecular profiles that were independent of tamoxifen exposure. Of recognized clinicopathological factors, histologic grade correlated best with these two molecular classes. Conclusions. These data suggest that the molecular profile of tamoxifen-associated endometrial,cancers is not different from that of endometrial carcinomas generally, and further, that there exist two highly distinct molecular subtypes of endometrial carcinoma. (C) 2003 Elsevier Inc. All rights reserved.