Affiliations: Department of General Surgery, University of
Göttingen, Göttingen, Germany | Department of Pathology, Thomas Jefferson University,
Philadelphia, PA, USA | Department of Pathology, University of Regensburg,
Germany | Department of Pathology, University of Bonn,
Germany | Kimmel Cancer Institute, Thomas Jefferson University,
Philadelphia, PA, USA | Department of Pathology, Klinikum Kassel, Kassel,
Germany
Note: [] Corresponding author: Prof. Dr. Josef Rüschoff, Intsitute of
Pathology, Klinikum Kassel, Moenchebergstr. 41-43, D-34125 Kassel, Germany.
Tel.: +49 561 980 4001; Fax: +49 561 980 6983; E-mail:
ruesch@klinikum-kassel.de
Abstract: 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.
