Published online before print June 13, 2008

This Article Full Text (Rapid PDF) All Versions of this Article: jmoldx.2008.080062v1 10/4/301    most recent 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 Google Scholar Articles by Zhang, L. PubMed PubMed Citation Articles by Zhang, L. Related Collections Related Article

Copyright © 2008 American Society for Investigative Pathology
Journal of Molecular Diagnostics, doi:10.2353/jmoldx.2008.080062

Accepted for publication April 28, 2008.

Article

Immunohistochemistry versus Microsatellite Instability Testing for Screening Colorectal Cancer Patients at Risk for Hereditary Nonpolyposis Colorectal Cancer Syndrome. Part II. The Utility of Microsatellite Instability Testing

From the Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York

^@ To whom correspondence should be addressed. E-mail: zhangl2{at}mskcc.org.

	Abstract

Germline mutations in the mismatch repair genes mutL homolog 1 (MLH1) and mutS homolog 2 (MSH2), MSH6, and postmeiotic segregation increased 2 (PMS2) lead to the development of hereditary nonpolyposis colorectal cancer (HNPCC). Diagnosis of HNPCC relies on the compilation of a thorough family history of cancer, documentation of pathological findings, tumor testing for microsatellite instability (MSI) and immunohistochemistry (IHC), and germline mutation analysis of the suspected genes. As a hallmark of HNPCC, microsatellite instability is widely accepted as a primary method for identifying individuals at risk for HNPCC. It serves as an excellent, easy-to-evaluate marker of mismatch repair deficiency. Recent improvements in MSI testing have significantly enhanced the accuracy and reduced its cost. Proficiency testing for MSI is available, and laboratory-to-laboratory reproducibility of such testing can be easily evaluated. In addition, the combination of microsatellite instability testing, MLH1 promoter methylation analysis, and BRAF (V600E) mutation analysis can distinguish a sporadic colorectal cancer from one associated with HNPCC, helping to avoid costly molecular genetic testing for germline mutations in mismatch repair genes. In this article, we discuss the development of MSI markers used for HNPCC screening and focus on the advantages and disadvantages of MSI testing in screening for HNPCC patients. We conclude that MSI is as sensitive and specific as IHC, given its excellent reproducibility and its potential capability to indicate mutations not be detected by IHC. MSI has been used and will continue to prevail as the primary screening tool for identifying HNPCC patients.

This article has been cited by other articles:

				W. He, Y. Zhao, C. Zhang, L. An, Z. Hu, Y. Liu, L. Han, L. Bi, Z. Xie, P. Xue, et al. Rad9 plays an important role in DNA mismatch repair through physical interaction with MLH1 Nucleic Acids Res., November 1, 2008; 36(20): 6406 - 6417. [Abstract] [Full Text] [PDF]