K‐ras mutation in tamoxifen‐related endometrial polyps

• Published in: Cancer 2003-11, Vol.98 (9), p.1890-1897
• Main Authors: Hachisuga, Toru, Miyakawa, Takashi, Tsujioka, Hiroshi, Horiuchi, Shinji, Emoto, Makoto, Kawarabayashi, Tatsuhiko
• Format: Article
• Language: English
• Subjects: Aged; Antineoplastic Agents, Hormonal - adverse effects; Biological and medical sciences; Breast Neoplasms - diet therapy; Codon; Drug toxicity and drugs side effects treatment; Endometrial Neoplasms - chemically induced; Endometrial Neoplasms - genetics; endometrial polyp; estrogen receptor; Female; Genes, ras; Humans; Immunohistochemistry; K-ras gene; K‐ras; Medical sciences; Middle Aged; Miscellaneous (drug allergy, mutagens, teratogens...); Mutation; Pharmacology. Drug treatments; Polyps - chemically induced; Polyps - genetics; Precancerous Conditions - genetics; Receptors, Estrogen - analysis; Receptors, Progesterone - analysis; tamoxifen; Tamoxifen - adverse effects
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.11728

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; α and β 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‐α 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‐β appeared to be lower than expression of ER‐α. 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‐α, 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. Cancer 2003. © 2003 American Cancer Society. Mutations in codon 12 of K‐ras were observed in 7 of 11 tamoxifen (TAM)‐related endometrial polyps. 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.