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 Stefansson, I. Articles by Salvesen, H. B. Search for Related Content PubMed PubMed Citation Articles by Stefansson, I. Articles by Salvesen, H. B.

Loss of hMSH2 and hMSH6 Expression Is Frequent in Sporadic Endometrial Carcinomas with Microsatellite Instability

A Population-based Study¹

Department of Pathology, The Gade Institute [I. S., L. A. A., H. B. S.]; Department of Gynecology and Obstetrics, Haukeland University Hospital, N-5021 Bergen, Norway [H. B. S.]; Gynaecology Cancer Research Unit, Department of Gynaecological Oncology, St. Bartholomew’s Hospital and The Royal London Hospital School of Medicine and Dentistry, London EC1A 7BE, United Kingdom [N. M., A. R., I. J. J.]; and Department of Human Genetics, The University of Chicago, Chicago, Illinois 60637 [S. D.]

Microsatellite instability (MSI) seems to be important in the development of various human cancers including sporadic endometrial cancer. It has previously been shown that alterations in the mismatch repair gene hMLH1 seem to be important for the development of MSI in these tumors. The role of the other mismatch repair genes hMSH2 and hMSH6 has been less well studied, but investigations on patients with hereditary nonpolyposis colorectal cancer indicate that these genes also may be involved. We therefore wanted to investigate the pattern of hMSH2 and hMSH6 expression in a prospective and population-based series of endometrial carcinomas with known hMLH1 expression and MSI status. A total of 138 patients were studied, and pathological staining was seen in 19 cases (14%) for hMLH1, 26 cases (19%) for hMSH2, and 17 cases (12.3%) for hMSH6. Pathological hMLH1 expression was more frequent among tumors with high MSI (those positive for four to five of five markers), whereas pathological expression of hMSH2 and hMSH6 was more frequent among tumors with intermediate MSI (those positive for two to three of five markers). MSI was significantly correlated with pathological expression of hMLH1 (P < 0.001), hMSH2 (P = 0.04), and hMSH6 (P = 0.001). In the group with high MSI, 14 of 16 tumors (88%) showed pathological expression for at least one of the markers. The expression of hMLH1, hMSH2, or hMSH6 did not significantly influence survival. In conclusion, pathological expression of hMLH1 does not seem to account for all tumors with a MSI-positive phenotype in this population-based series of endometrial carcinomas. Our data indicate that the other mismatch repair genes hMSH2 and hMSH6 are also involved, especially in cases with intermediate MSI.

This article has been cited by other articles:

				J. Yu, M. A. Mallon, W. Zhang, R. R. Freimuth, S. Marsh, M. A. Watson, P. J. Goodfellow, and H. L. McLeod DNA Repair Pathway Profiling and Microsatellite Instability in Colorectal Cancer Clin. Cancer Res., September 1, 2006; 12(17): 5104 - 5111. [Abstract] [Full Text] [PDF]

				N. P. Taylor, M. A. Powell, R. K. Gibb, J. S. Rader, P. C. Huettner, S. N. Thibodeau, D. G. Mutch, and P. J. Goodfellow MLH3 Mutation in Endometrial Cancer. Cancer Res., August 1, 2006; 66(15): 7502 - 7508. [Abstract] [Full Text] [PDF]

				M. Ollikainen, W. M. Abdel-Rahman, A.-L. Moisio, A. Lindroos, R. Kariola, I. Jarvela, M. Poyhonen, R. Butzow, and P. Peltomaki Molecular Analysis of Familial Endometrial Carcinoma: A Manifestation of Hereditary Nonpolyposis Colorectal Cancer or a Separate Syndrome? J. Clin. Oncol., July 20, 2005; 23(21): 4609 - 4616. [Abstract] [Full Text] [PDF]

				B. M. Buttin, M. A. Powell, D. G. Mutch, J. S. Rader, T. J. Herzog, R. K. Gibb, P. Huettner, T. B. Edmonston, and P. J. Goodfellow Increased Risk for Hereditary Nonpolyposis Colorectal Cancer-Associated Synchronous and Metachronous Malignancies in Patients with Microsatellite Instability-Positive Endometrial Carcinoma Lacking MLH1 Promoter Methylation Clin. Cancer Res., January 15, 2004; 10(2): 481 - 490. [Abstract] [Full Text] [PDF]

				P. J. Goodfellow, B. M. Buttin, T. J. Herzog, J. S. Rader, R. K. Gibb, E. Swisher, K. Look, K. C. Walls, M.-Y. Fan, and D. G. Mutch Prevalence of defective DNA mismatch repair and MSH6 mutation in an unselected series of endometrial cancers PNAS, May 13, 2003; 100(10): 5908 - 5913. [Abstract] [Full Text] [PDF]