K-ras Mutations Common In Tamoxifen-related Endometrial Polyps

NEW YORK (Reuters Health) - Tamoxifen may influence the development of endometrial cancer by causing mutations in the K-ras gene, according to a report in the November 1st issue of Cancer.

Postmenopausal breast cancer patients treated with tamoxifen face an increased risk of endometrial carcinoma, the authors explain, but it is not known whether these tumors result from tamoxifen adducts to DNA or because of the estrogenic nature or both.

Because K-ras mutations are thought to occur at an early stage of endometrial oncogenesis, Dr. Toru Hachisuga and colleagues from Fukuoka University, Japan sought mutations in K-ras in 11 frozen endometrial polyps from tamoxifen-treated patients with breast cancer.

Seven of the 11 tamoxifen-related endometrial polyps contained mutations in codon 12 of K-ras, the authors report. All of the mutations were in the second base of codon 12.

"Among the observed mutations in codon 12 of K-ras, four were identified as GGT to GAT mutations and two were identified as GGT to GCT mutations," the researchers note. "In contrast, in previous studies, GGT to GTT was found to be the most common mutation in sporadic endometrial hyperplasias."

Immunohistochemical findings included high expression levels of estrogen receptor-alpha in the glandular epithelium and progesterone receptor-A in both the glandular epithelium and the stroma, whereas estrogen receptor-beta was expressed at lower levels and progesterone receptor-B expression was high in the glandular epithelium and low in the stroma.

"These histochemical findings were consistent with the findings for hormone receptors in glandular epithelium in the proliferative phase," the investigators explain.

Dr. Hachisuga told Reuters Health that the team suspects that endometrial cancer might be initiated from cooperation with mutagenic activity of tamoxifen-DNA adducts and the estrogenic effect of tamoxifen. K-ras mutation may be one manifestation of the pathway of carcinogenesis of tamoxifen-related endometrium, he said.

Dr. Hachisuga cautioned that the study was small, and said that the next step is to examine K-ras mutations in larger numbers of tamoxifen-related endometriums.

Source: Cancer 2003;09:1890-1897. [ Google search on this article ]

MeSH Headings: Genital Neoplasms, Female : Neoplasms : Neoplasms by Site : Genes, ras : Urogenital Neoplasms : Uterine Neoplasms : Endometrial Neoplasms : Diseases