This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted 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 Hirasawa, A. Articles by Inazawa, J. Search for Related Content PubMed PubMed Citation Articles by Hirasawa, A. Articles by Inazawa, J.

Unfavorable Prognostic Factors Associated with High Frequency of Microsatellite Instability and Comparative Genomic Hybridization Analysis in Endometrial Cancer

¹ Department of Molecular Cytogenetics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo;
² Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo;
³ Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama; and
⁴ Oncogene Research Unit/Cancer Prevention Unit, Tochigi Cancer Center Research Institute, Tochigi, Japan

Purpose: Although many articles have been published regarding chromosomal instability (CI) and microsatellite instability (MI) in endometrial adenocarcinoma, the relationship between prognostic factors and the biological mechanisms accounting for genetic instability in these tumors has not yet been precisely defined. To do that, it will be necessary to clarify the molecular mechanisms involved in endometrial carcinogenesis.

Experimental Design: Tissue samples from 43 human primary endometrioid endometrial adenocarcinomas (EACs) were analyzed for CI and MI status using comparative genomic hybridization and 11 microsatellite loci, respectively. Methylation status of the promoter of MLH1 was also determined. We analyzed all three of these parameters in relation to each other and to clinicopathological factors.

Results: Sixty-five percent of the EACs we examined had detectable CI. Frequent copy number gains were seen at 1q25–41 (23%), 8q11.1-q21.1 (23%), 8q21.3-qter (21%); 28% of these tumors exhibited high-frequency MI (MSI-H); Methylation of the MLH1 promoter was observed in 92% of EACs with MSI-H. Southern blotting showed amplification of MYCN in one tumor, which has been documented for the first time in a primary human EAC.

Conclusions: MSI-H was correlated with histological grade, International Federation of Gynecologists and Obstetricians (FIGO) stage, myometrial invasion, and lymphonode metastasis. Our comparative genomic hybridization results demonstrated that the number of chromosomes involved in genomic alterations in EACs was distinctively fewer than those in other types of tumor. The carcinogenetic process leading to EAC appears to be highly complex; for example, MI and CI may act synergistically, whereas CI and/or MI are likely to be linked with tumor heterogeneity.

This article has been cited by other articles:

				J. I. Risinger, G. L. Maxwell, G. V.R. Chandramouli, O. Aprelikova, T. Litzi, A. Umar, A. Berchuck, and J. C. Barrett Gene Expression Profiling of Microsatellite Unstable and Microsatellite Stable Endometrial Cancers Indicates Distinct Pathways of Aberrant Signaling Cancer Res., June 15, 2005; 65(12): 5031 - 5037. [Abstract] [Full Text] [PDF]

				T. Iwata, T. Fujita, N. Hirao, Y. Matsuzaki, T. Okada, H. Mochimaru, N. Susumu, E. Matsumoto, K. Sugano, N. Yamashita, et al. Frequent Immune Responses to a Cancer/Testis Antigen, CAGE, in Patients with Microsatellite instability-Positive Endometrial Cancer Clin. Cancer Res., May 15, 2005; 11(10): 3949 - 3957. [Abstract] [Full Text] [PDF]