Genetic imbalances in endometrial hyperplasia and endometrioid carcinoma detected by comparative genomic hybridization Hamza M. Muslumanoglu a , U. Oner b , S. Ozalp c , M.F. Acikalin b , O.T. Yalcin c , M. Ozdemir a , S. Artan a, * a Department of Medical Genetics, Osmangazi University Medical Faculty, 26480 Eskisehir, Turkey b Department of Pathology, Osmangazi University Medical Faculty, Eskisehir, Turkey c Department of Obstetrics and Gynecology, Osmangazi University Medical Faculty, Eskisehir, Turkey Received 12 February 2004; received in revised form 28 May 2004; accepted 5 August 2004 Abstract Objective: To evaluate the sequential genomic copy alterations related to the development of precursor lesions and endometrioid-type endometrial carcinomas, and its association with cellular atypia. Study design: Paraffin-embedded tissue specimens from 32 cases of endometrial hyperplasia, 15 of endometrial carcinoma, and 20 of normal endometrial tissue were retrospectively evaluated by the comparative genomic hybridization (CGH) technique. The average number of copy alterations (ANCA) index was used to define the incidence of genomic imbalances in each tissue group. Identified sequential genetic abnormalities were compared with the final histopathological diagnosis and the cellular atypia. Results: Detectable and consistent chromosomal imbalances were found in 13 hyperplasia and 9 carcinoma specimens. There was a significant correlation between ANCA value and degree of cellular atypia and tumor grade. While 1p36-pter, 20q deletions, and 4q overrepresentation were the most prevalent imbalances detected in both complex hyperplasia and complex atypical hyperplasia, 17q22-qter deletion and amplification of 2p34 were only seen in hyperplasia with atypical cells. Overrepresentations of chromosomes 8q, 1q, and 3q are the most frequent aberrations in endometrial carcinomas, but were absent from all the precursor lesions except one. Underrepresentations of chromosomes 1p36-pter and 10q are the other commonly seen aberrations in carcinomas, the latter being more frequent in moderately differentiated than in poorly differentiated lesions. Conclusions: Different patterns of chromosomal aberrations are seen in precursor lesions than in endometrial carcinomas, except for the loss of 1p36-pter. The presence of 1p deletion in both endometrial hyperplasia and cancer specimens suggests that this is an early event in the development of carcinoma. These results support a stepwise mode of tumorigenesis with accumulation of a series of genomic copy alterations in endometrial carcinogenesis. # 2004 Elsevier Ireland Ltd. All rights reserved. Keywords: Genomic copy aberrations; Endometrial hyperplasia; Endometrial carcinoma; Comparative genomic aberrations; Endometrial carcinogenesis 1. Introduction Endometrial carcinoma is the most common malignancy of the female genital tract. In the past two decades, clinicopathological, immunohistochemical, and molecular genetic studies have provided new data, allowing for the development of a dualistic model of endometrial carcino- genesis. In this model, atypical hyperplasia is recognized as the precursor for the endometrioid type of endometrial carcinoma, and endometrial intraepithelial carcinoma, as the precursor for serous carcinoma [1]. On the other hand, Mutter et al. [2] have proposed that endometrial prolifera- tions be broadly divided into monoclonal and polyclonal subgroups on the basis of the molecular genetic analysis of clonality. Polyclonal proliferations are designated ‘hyper- plasia’, and monoclonal proliferations, ‘endometrial intrae- pithelial neoplasia’ (EIN) and have an elevated risk of progression to carcinoma. However, because clonality cannot be routinely performed on diagnostic specimens, www.elsevier.com/locate/ejogrb European Journal of Obstetrics & Gynecology and Reproductive Biology 120 (2005) 107–114 * Corresponding author. Tel.: +90 222 239 3771; fax: +90 222 239 2986. E-mail address: sartan@ogu.edu.tr (S. Artan). 0301-2115/$ – see front matter # 2004 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ejogrb.2004.08.015