Changes in expression of estrogen receptors alpha and beta in relation to progesterone receptor and pS2 status in normal and malignant endometrium

To clarify changes in estrogen receptor (ER) alpha and ER beta during endom etrial tumorigenesis, 48 endometrial carcinomas (endometrioid type), as web as 40 samples of normal endometrial tissue, were investigated using a comb ination of reverse-transcription and polymerase chain reaction with Souther n blot hybridization and western blot assays, and the results were compared with findings for progesterone receptor (PR) and pS2 mRNA status. In addit ion, 166 carcinomas were also examined for immunohistochemistry; along with 171 normal specimens. Relative amounts of ER alpha at both mRNA and protei n levels were significantly greater than those for ER beta in normal and ma lignant endometrial lesions. ER alpha mRNA showed a stepwise decrease from normal or grade (G) 1 through to G3 tumor lesions, in line with changes in the protein levels, in contrast to ER beta mRNA or protein expression, whic h did not alter, suggesting a shift in the ratio of the two ER subtypes dur ing endometrial tumorigenesis. PR mRNA expression was significantly correla ted with ER alpha, but not ER beta mRNA status. Although significantly high er expression of pS2 mRNA or protein was observed in carcinomas than in the normal cases, there was no apparent association with the ER status. The fi ndings suggest that alteration in estrogen signaling pathways may occur dur ing endometrial tumorigenesis, and provide evidence that ER alpha expressio n may play an important role in the regulation of PR, but not pS2 expressio n in normal and malignant endometrium.