hMLH1 promoter methylation status causes different expression patterns of estrogen receptor protein with endometrial lesion progression.

Mismatch repair (MMR) deficiency is reported to be an important factor in the early process of endometrial carcinogenesis. Although estrogen exposure is a crucial risk factor for endometrial carcinoma (EMCa), estrogen function is mediated by the estrogen receptor (ER). However, the relationship between ER and MMR, such as hMLH1 (human mutL homolog 1) activity, remains undetermined. In this study, we investigated the relationship between ER expression and hMLH1 promoter methylation status in atypical hyperplasia (AEH) and EMCa. ER expression was examined by immunohistochemical staining and the hMLH1 methylation status was evaluated using a methylation-specific PCR method. ER expression was significantly high in AEH, and extremely decreased with progression to EMCa. The hMLH1 methylation status allowed classification into methylated and unmethylated groups. Regarding the relationship between ER expression and hMLH1 methylation status, ER expression differed significantly between AEH and EMCa, and decreased with progression of the lesion in the unmethylated group, while it did not decrease with progression in the methylated group. These findings suggest that for a precursor lesion with hMLH1 unmethylated status, a decrease in ER expression is important for the development of carcinogenesis, while progression of a lesion with hMLH1 methylated status is not affected by ER expression.