Atypical endometrial hyperplasia shares genomic abnormalities with endometrioid carcinoma by comparative genomic hybridization

Endometrial hyperplasia is a common disorder that is no cv observed with in creasing frequency in women treated with hormonal replacement therapy or wi th tamoxifen. This study was undertaken to determine whether genomic featur es of various forms of endometrial hyperplasias would allow their classific ation as a benign, premalignant, or malignant abnormality. Comparative geno mic hybridization (CGH) was performed on endometrial glands microdissected by laser capture microscope from 19 archival endometrial samples, comprisin g 5 normal endometria, 1 polyp, 2 simple hyperplasias, 5 hyperplasias with nuclear abnormalities (atypical hyperplasias), and 4 low-grade and 2 high-g rade endometrioid carcinomas, 1 with squamous component (adenoacanthoma). G enomic DNA, extracted from the glands and the squamous component in I case, was amplified by degenerate olignonucleotide-primed polymerase chain react ion (DOP-PCR) and compared with sex-matched DNA by CGH. No genomic imbalanc es were observed in the normal samples, the polyp, or the simple hyperplasi as. However, in atypical hyperplasia, regardless of the level of cytologic atypia, genomic abnormalities were observed that;also occurred in endometri oid carcinomas. Chromosomes 1, 8, and 10 were most often affected. The resu lts are compared with molecular genetic abnormalities recently reported in these lesions. This study strongly suggests that atypical endometrial hyper plasias are closely related to endometrioid carcinoma and should be conside red precancerous lesions, contrary to simple hyperplasia, which is a benign disorder. The squamous component of one of the high-grade carcinomas showe d genetic abnormalities similar to those of endometrioid carcinoma and ther efore does not represent squamous metaplasia but is an integral part of the malignant process. Copyright (C) 2001 by W.B. Saunders Company.