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.
Department of Obstetrics and Gynecology, School of Medicine, Fukuoka University, Fukuoka, Japan. hachisug@fukuoka-u.ac.jp
Toru
T
Hachisuga
Takashi
T
Miyakawa
Hiroshi
H
Tsujioka
Shinji
S
Horiuchi
Makoto
M
Emoto
Tatsuhiko
T
Kawarabayashi
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