K-ras mutation in tamoxifen-related endometrial polyps.

Abstract

K-ras mutation is thought to occur at an early stage of neoplastic progression in the endometrium. The authors investigated mutations in codon 12 of K-ras in tamoxifen (TAM)-related endometrial polyps. DNA was extracted from 11 frozen endometrial polyps from TAM-treated patients with breast carcinoma. Mutations were detected using the mutant allele-specific amplification method. The results subsequently were analyzed for correlations with immunohistochemical data that were obtained using antibodies against estrogen receptors (ERs; alpha and beta forms), progesterone receptors (PRs; A and B forms), and Ki-67. Mutations in codon 12 of K-ras were observed in 7 of 11 TAM-related endometrial polyps. Expression levels of ER-alpha and PR-B were high in the glandular epithelium and low in the stroma. PR-A expression was high in both the glandular epithelium and the stroma. In the glandular epithelium, expression of ER-beta appeared to be lower than expression of ER-alpha. The Ki-67 index in the glandular epithelium ranged from 2 to 38, whereas the index ranged from 0 to 4 in the stroma (P < 0.01). The incidence of mutations in codon 12 of K-ras in TAM-related endometrial polyps (64%) was greater than the incidence of these same mutations in sporadic endometrial hyperplasias (4.5-23%). High expression levels of ER-alpha, PR-A, and PR-B in the glandular epithelium were observed in all polyps, regardless of K-ras codon 12 mutation status and Ki-67 index. The authors' findings may support the hypothesis that the polyp-carcinoma sequence partly indicates the development of endometrial carcinoma in postmenopausal women who have been treated with TAM.