Molecular profiling of estrogen receptor α and progesterone receptor transcript variants in endometrial cancer.

The human genes coding for estrogen receptor alpha (ERα) and progesterone receptor (PR) express multiple receptor splice variants. Some of these receptor variants previously have been shown to exert distinct functions in cancer cells and might therefore differentially affect individual prognosis or therapy response. To examine the role of ERα- and PR-isoforms in endometrial cancer, we compared the expression of 19 ERα transcripts and 15 PR mRNA isoforms in human endometrium and in endometrioid endometrial cancer. Expression of seven ERα splice variants, total PR and of five PR transcript isoforms was found to be significantly decreased in endometrial cancer. In endometrioid G3 tumors, expression of 17 ERα and 10 PR splice variants was reduced when compared to normal tissue. Notably, only 13% of G3 tumors did not express any ERα variant and only in 25% of G3 samples no PR transcripts were expressed. Seven splice variants were preferentially expressed in G1 and G2 tumors. In G1 tumors, a higher number of different ERα and PR splice variants was expressed than in normal endometrium, G2 or G3 tumors. Expression of total PR and of single PR splice variants was found to be positively associated with PTEN. Our results encourage further studies to elucidate to what extent the heterogeneous co-expression profiles we found in endometrial cancer patients differentially affect both individual prognosis and therapy response.