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Disease Markers
Volume 20, Issue 4-5, Pages 225-236

MSI-Testing in Hereditary Non-Polyposis Colorectal Carcinoma (HNPCC)

Annegret Müller,1 Tina Bocker Edmonston,2 Wolfgang Dietmaier,3 Reinhard Büttner,4 Richard Fishel,5 and Josef Rüschoff6

1Department of General Surgery, University of Göttingen, Göttingen, Germany
2Department of Pathology, Thomas Jefferson University, Philadelphia, PA, USA
3Department of Pathology, University of Regensburg, Germany
4Department of Pathology, University of Bonn, Germany
5Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, PA, USA
6Department of Pathology, Klinikum Kassel, Kassel, Germany

Received 26 October 2004; Accepted 26 October 2004

Copyright © 2004 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Genomic instability at simple repeated sequences, termed microsatellite instability (MSI), plays an important role in the analysis of sporadic and hereditary colon cancers. In hereditary non-polyposis colorectal cancer syndrome (HNPCC) more than 90% of cases show MSI, whereas only 10–15% of sporadic colorectal cancers do so. Thus, microsatellite analysis is commonly used as the first diagnostic screening test for HNPCC. In 1997, an international collaborative workshop sponsored by the National Cancer Institute (NCI) proposed a set of guidelines for MSI-testing to improve reliability and reproducibility of the analysis as well to allow comparisons between different studies and different laboratories. In this review we assess the value of current protocols forMSI-testing and discuss some diagnostic pitfalls. Our findings support continued use of the MSI marker panel recommended in 1997. Additionally, MSI-testing should be improved by use of microdissection, which helps to identify additional patients with MSI due to enrichment of tumor cells and therefore increased sensitivity. In our view, immunohistochemical staining for mismatch repair protein expression is not a substitute for MSI-analysis but complements MSI screening and helps direct further testing. In summary, MSI-analysis is a highly sensitive and reliable screening method for HNPCC, that requires a well-equipped laboratory as well as an experienced pathologist. Integration of family history and histo-pathological features is also critical.