Alterations of the K-ras and p53 genes in Tamoxifen-associated endometrial carcinoma.
To better understand the molecular mechanisms of carcinogenesis induced in uterine endometrium by therapeutic anti-estrogenic Tamoxifen (TAM) exposure, 27 uterine tumors (4 benign endometrial polyps and 23 carcinomas) associated with TAM exposure were analyzed for the presence and spectrum of p53 and K-ras mutations. Although there was no significant difference between TAM-associated endometrial carcinomas and sporadic endometrial tumors in the frequency of these mutations, the spectrum of p53 mutations was characteristically unique to the TAM-associated tumors. The median duration of TAM exposure was significantly longer in patients with p53 mutations than those without p53 mutations (62 vs. 30 months, p=0.028). Our observation suggests that prolonged TAM exposure may directly inactivate the p53 gene by acting as a mutagen in a significant fraction of TAM-associated endometrial carcinomas.
Fujiwara
Kazuko
K
Department of Obstetrics and Gynecology, Osaka University, Graduate School of Medicine, Faculty of Medicine, Osaka 565-0871, Japan.
Enomoto
Takayuki
T
Fujita
Masami
M
Kanda
Takayoshi
T
Fujii
Shingo
S
Ito
Kimihiko
K
Wakasa
Kenichi
K
Ishiko
Osamu
O
Ueda
Masatsugu
M
Yamaguchi
Satoshi
S
Kimura
Tadashi
T
Umesaki
Naohiko
N
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects*; D002277:Carcinoma / Q000139:chemically induced* / Q000378:metabolism*; D016889:Endometrial Neoplasms / Q000139:chemically induced* / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D011905:Genes, ras; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D013629:Tamoxifen / Q000009:adverse effects*
D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen