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


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).


CONCLUSIONS
Methylation of the CpG island of the ER gene is inversely correlated with ER expression in a subset of endometrial carcinomas.
Shiozawa
Tanri
T
Department of Obstetrics and Gynecology, Shinshu University School of Medicine, Matsumoto, Japan. tanri@hsp.md.shinshu-u.ac.jp
Itoh
Kazuko
K
Horiuchi
Akiko
A
Konishi
Ikuo
I
Fujii
Shingo
S
Nikaido
Toshio
T
D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D047628:Estrogen Receptor alpha; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000096:biosynthesis / Q000235:genetics*; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D047628:Estrogen Receptor alpha; D012333:RNA, Messenger; D011960:Receptors, Estrogen