K-ras mutation in tamoxifen-related endometrial polyps.
BACKGROUND
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Hachisuga
Toru
T
Department of Obstetrics and Gynecology, School of Medicine, Fukuoka University, Fukuoka, Japan. hachisug@fukuoka-u.ac.jp
Miyakawa
Takashi
T
Tsujioka
Hiroshi
H
Horiuchi
Shinji
S
Emoto
Makoto
M
Kawarabayashi
Tatsuhiko
T
D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000178:diet therapy; D003062:Codon; D016889:Endometrial Neoplasms / Q000139:chemically induced / Q000235:genetics*; D005260:Female; D011905:Genes, ras; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009154:Mutation; D011127:Polyps / Q000139:chemically induced / Q000235:genetics*; D011230:Precancerous Conditions / Q000235:genetics; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D013629:Tamoxifen / Q000009:adverse effects*
D018931:Antineoplastic Agents, Hormonal; D003062:Codon; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen