title: MSI-testing in hereditary non-polyposis colorectal carcinoma (HNPCC).
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 for MSI-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.
authors.affiliation: Department of General Surgery, University of Göttingen, Göttingen, Germany.
authors.forename: Annegret
authors.initials: A
authors.lastname: Müller
authors.forename: Tina Bocker
authors.initials: TB
authors.lastname: Edmonston
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Dietmaier
authors.forename: Reinhard
authors.initials: R
authors.lastname: Büttner
authors.forename: Richard
authors.initials: R
authors.lastname: Fishel
authors.forename: Josef
authors.initials: J
authors.lastname: Rüschoff
mesh_terms: D000236:Adenoma / Q000235:genetics; D014408:Biomarkers, Tumor; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis* / Q000235:genetics*; D017931:DNA Primers / Q000737:chemistry; D043243:DNA Sequence, Unstable; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D006801:Humans; D007150:Immunohistochemistry; D042282:Microdissection; D018895:Microsatellite Repeats; D008954:Models, Biological; D008957:Models, Genetic; D000074081:MutS Homolog 3 Protein; D009154:Mutation; D010641:Phenotype; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D017931:DNA Primers; D004268:DNA-Binding Proteins; C078444:MSH3 protein, human; D000074081:MutS Homolog 3 Protein