Down-regulation of estrogen receptor by the methylation of the estrogen receptor gene in endometrial carcinoma.

摘要

BACKGROUND: Human uterine endometrial carcinomas are composed of estrogen receptor (ER)-positve and ER-negative subgroups, though the mechanisms that down-regulate the ER expression are not understood. The present study was undertaken to examine the involvement of methylation of the ER gene on the ER status. MATERIALS AND METHODS: DNA was extracted from 25 cases of endometrial carcinoma. Polymerase chain reaction (PCR), using the extracted DNA and methylation-sensitive restriction enzymes (Hpa II, Hha I), was performed to detect the methylation of a CpG island in the ER (alpha) gene. The results were compared with the ER expression by immunostaining. RESULTS: In the 25 endometrial carcinomas, methylation at the Hpa II site, or at both the Hpa II and Hha I sites, was found in 6 cases, while methylation was not found in the remaining 19 cases. Immunohistochemically, 5 of the 6 methylation-positive cases were negative for ER, whereas 14 of the 19 methylation-negative cases were ER-positive (p=0.02). CONCLUSION: Methylation of the CpG island of the ER gene is inversely correlated with ER expression in a subset of endometrial carcinomas.