This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kiechle, M. Articles by Arnold, N. Search for Related Content PubMed PubMed Citation Articles by Kiechle, M. Articles by Arnold, N.

(American Journal of Pathology. 2000;156:1827-1833.)
© 2000 American Society for Investigative Pathology

Short Communications

Genetic Imbalances in Precursor Lesions of Endometrial Cancer Detected by Comparative Genomic Hybridization

Marion Kiechle^*, Maren Hinrichs^*, Anja Jacobsen^*, Jutta Lüttges, Jacobus Pfisterer^*, Friedrich Kommoss and Norbert Arnold^*

From the Departments of Gynecology and Obstetrics^*
and Pathology,
University of Kiel, Kiel; and the Department of Pathology,
University of Mainz, Mainz, Germany

Endometrial hyperplasia is regarded as a precursor lesion of endometrioid adenocarcinomas of the endometrium. The genetic events involved in the multistep process from normal endometrial glandular tissue to invasive endometrial carcinomas are primarily unknown. We chose endometrial hyperplasia as a model for identifying chromosomal aberrations occurring during carcinogenesis. Comparative genomic hybridization (CGH) was performed on 47 formalin-fixed, paraffin-embedded specimens of endometrial hyperplasia using the microdissection technique to increase the number of tumor cells in the samples and reduce contamination from normal cells. CGH analysis revealed that 24 out of 47 (51%) samples had detectable chromosomal imbalances, whereas 23 (49%) were in a genetically balanced state. The incidence of aberrant CGH profiles tended to parallel dysplasia grade, ranging from 22% aberrant profiles in simple hyperplasia to 67% in complex hyperplasia with atypia. The most frequent imbalances were 1p, 16p, and 20q underrepresentations and 4q overrepresentations. Copy number changes in 1p were more frequent in atypical complex hyperplasia than in complex lesions without atypical cells or simple lesions (42% versus 20% and 0%). Our results show that endometrial hyperplasia reveals recurrent chromosomal imbalances which tend to increase with the presence of atypical cells. The most frequent aberrations in endometrial cancer, 1q and 8q overrepresentations, are not present or are rare in its precursor lesions. This analysis provides evidence that tumorigenesis proceeds through the accumulation of a series of genetic alterations and suggests a stepwise mode of tumorigenesis.

This article has been cited by other articles:

				A. Hirasawa, D. Aoki, J. Inoue, I. Imoto, N. Susumu, K. Sugano, S. Nozawa, and J. Inazawa Unfavorable Prognostic Factors Associated with High Frequency of Microsatellite Instability and Comparative Genomic Hybridization Analysis in Endometrial Cancer Clin. Cancer Res., November 15, 2003; 9(15): 5675 - 5682. [Abstract] [Full Text] [PDF]

				C. L. Andersen, O. Monni, U. Wagner, J. Kononen, M. Barlund, C. Bucher, P. Haas, A. Nocito, H. Bissig, G. Sauter, et al. High-Throughput Copy Number Analysis of 17q23 in 3520 Tissue Specimens by Fluorescence in Situ Hybridization to Tissue Microarrays Am. J. Pathol., July 1, 2002; 161(1): 73 - 79. [Abstract] [Full Text] [PDF]

				R. L. Arnett-Mansfield, A. deFazio, G. V. Wain, R. C. Jaworski, K. Byth, P. A. Mote, and C. L. Clarke Relative Expression of Progesterone Receptors A and B in Endometrioid Cancers of the Endometrium Cancer Res., June 1, 2001; 61(11): 4576 - 4582. [Abstract] [Full Text] [PDF]

				L. A. Loeb A Mutator Phenotype in Cancer Cancer Res., April 1, 2001; 61(8): 3230 - 3239. [Abstract] [Full Text]