Diagnostic microsatellite instability: Definition and correlation with mismatch repair protein expression

  • Dietmaier W
  • Wallinger S
  • Bocker T
 et al. 
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Abstract

Alterations of the length of simple repetitive genomic sequences (microsatellite instability, MSI) characterize a distinct mechanism of colorectal carcinogenesis. Such MSI has been found to be associated with hereditary nonpolyposis colorectal cancer (HNPCC) that involves mutation of the human mismatch repair genes hMSH2 and hMLH1 as well as many sporadic cancers of most tissue types. Although the study of MSI status is a useful tool for HNPCC screening and for the determination of tumor prognosis in sporadic cases of colorectal cancer, the reliability of MSI diagnosis is still a subject of debate. Here we have examined 58 primary colorectal tumors (selected from a cohort of 200) using 31 microsatellite markers that comprised the most frequent simple repeat types. The expression of the hMSH2 and hMLH1 mismatch repair proteins was studied by immunohistochemistry, and most patients were surveyed for at least 2 years. Reproducibility of gel interpretation, as well as diagnostic sensitivity and specificity of the MSI status, were determined. We found that unambiguous determination of band shifts as well as MSI diagnosis were closely related to the type of the marker repeat and that MSI could be subdivided into "high" MSI (>20% unstable loci), "low" MSI (

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