GENOMIC CHANGES IN ENDOMETRIAL POLYPS ASSOCIATED WITH TAMOXIFEN SHOW NO EVIDENCE FOR ITS ACTION AS AN EXTERNAL CARCINOGEN

Eighty-eight endometrial specimens from 36 postmenopausal breast cance r patients treated with tamoxifen were investigated cytogenetically an d molecularly using fluorescence in situ hybridization with appropriat e probes for the HMGIC and HMGIY genes. Twenty control specimens, IO e ndometrial polyps, and 10 endometrial biopsy specimens were investigat ed in the same way. Of the 88 specimens, 44 were from endometrial poly ps; 3 were from endocervical polyps; 7 were from cystic endometrium; 3 0 were from normal or atrophic endometrium, normal endocervix, or myom etrium; and 4 were from endometrial carcinomas, Chromosome investigati on of the endometrial polyps showed the nature of the chromosome chang es in tamoxifen-induced polyps to he the same as that in the controls and in sporadic endometrial polyps described in the literature. HMGIC and HMGIY gene rearrangements in both groups were identical as shown b y fluorescence in situ hybridization, which also allowed for the detec tion of seven hidden paracentric inversions involving 12q15, one of wh ich occurred in a cystic endometrium. The carcinomas did not exhibit a ny of these changes. Because abnormal expression of HMGIC or HMGIY as a consequence of structural chromosome changes in 12q15 or 6p21, respe ctively, is invariably associated with benign neoplasia, tamoxifen-ass ociated endometrial polyps are unlikely to undergo further malignant t ransformation, and a mode of action of tamoxifen as an external carcin ogen is unlikely.