title: Effects of tamoxifen on the endometrium and its mechanism of carcinogenicity.
abstract: This study was conducted to clarify the clinicopathological characteristics of tamoxifen-associated endometrial carcinomas and its mechanisms of carcinogenesis. Seven patients with tamoxifen-associated endometrial carcinomas (TAM group) and 28 with sporadic endometrioid adenocarcinomas (EMC group) were included in the study. The clinicopathological factors, such as FIGO stage, histological type, grade, lymph node metastases, vascular invasion and the coexistence of hyperplasia, were investigated in both groups. The protein expression of p53, PTEN, hMLH1 and hMSH2 was investigated by immunohistochemistry. Microsatellite instability (MSI), k-ras and p53 mutation were also examined. In the TAM group, the histological types included five endometrioid, one endometrioid combined with serous and one clear cell type. The rates of coexistence with hyperplasia (five of seven cases) and vascular invasion (four cases) were significantly higher in the TAM group. The rates of stage III/IV (four cases) and lymph node metastasis (three cases) tended to be higher in the TAM group. Although there were no significant differences in PTEN, hMLH1 and hMSH2 expression between the two groups, p53 mutation was more frequent in three out of five cases (60%) in the TAM group compared with 2 of 15 cases in the EMC group (13.3%). No significant differences were observed concerning MSI and k-ras mutation in either group. These results suggested that TAM-associated endometrial carcinomas have overlapping biological characteristics of type I and type II endometrial carcinomas. This might explain the somewhat worse prognosis of these tumors than sporadic endometrioid carcinomas.
authors.affiliation: Department of Obstetrics and Gynecology, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Yasue
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Hasegawa
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Udagawa
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D016889:Endometrial Neoplasms / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53 / Q000235:genetics; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D053842:Microsatellite Instability; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000378:metabolism; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D020845:Selective Estrogen Receptor Modulators / Q000009:adverse effects*; D013629:Tamoxifen / Q000009:adverse effects*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D020845:Selective Estrogen Receptor Modulators; D016159:Tumor Suppressor Protein p53; D013629:Tamoxifen; D051059:PTEN Phosphohydrolase; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein