Changes in Expression of Estrogen Receptors α and β in Relation to Progesterone Receptor and pS2 Status in Normal and Malignant Endometrium

To clarify changes in estrogen receptor (ER) α and ERβ during endometrial tumorigenesis, 48 endometrial carcinomas (endometrioid type), as well as 40 samples of normal endometrial tissue, were investigated using a combination of reverse‐transcription and polymerase chain reaction with Southern blot hybridization and western blot assays, and the results were compared with findings for progesterone receptor (PR) and pS2 mRNA status. In addition, 166 carcinomas were also examined for immunohistochemistry, along with 171 normal specimens. Relative amounts of ERα at both mRNA and protein levels were significantly greater than those for ERβ in normal and malignant endometrial lesions. ERα 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 ERβ mRNA or protein expression, which did not alter, suggesting a shift in the ratio of the two ER subtypes during endometrial tumorigenesis. PR mRNA expression was significantly correlated with ERα, but not ERβ mRNA status. Although significantly higher 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 findings suggest that alteration in estrogen signaling pathways may occur during endometrial tumorigenesis, and provide evidence that ERα expression may play an important role in the regulation of PR, but not pS2 expression in normal and malignant endometrium.