Microsatellite Instability and hMLH1 and hMSH2 expression analysis in familial and sporadic colorectal cancer

Lab Invest. 2001 Apr;81(4):535-41. doi: 10.1038/labinvest.3780262.


Immunohistochemical expression analysis of mismatch repair gene products has been suggested for the prediction of hereditary nonpolyposis colorectal cancer (HNPCC) carrier status in cancer families and the selection of microsatellite instability (MSI)-positive tumors in sporadic colorectal cancer. In this study, we aimed to evaluate hMSH2 and hMLH1 immunohistochemistry in familial and sporadic colorectal cancer. We found that immunohistochemistry allowed us to identify patients with germline mutations in hMSH2 and many cases with germline mutations in hMLH1. However, some missense and truncating mutations may be missed. In addition, hMLH1 promoter methylation, commonly occurring in familial and sporadic MSI-positive colorectal cancer, can complicate the interpretation of immunohistochemical expression analyses. Our results suggest that immunohistochemistry cannot replace testing for MSI to predict HNPCC carrier status or identify MSI-positive sporadic colorectal cancer.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • Colorectal Neoplasms / diagnosis*
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms, Hereditary Nonpolyposis / diagnosis*
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics*
  • Colorectal Neoplasms, Hereditary Nonpolyposis / metabolism
  • DNA Methylation
  • DNA, Neoplasm / chemistry
  • DNA-Binding Proteins*
  • Gene Expression Regulation, Neoplastic
  • Germ-Line Mutation
  • Humans
  • Immunohistochemistry
  • Microsatellite Repeats*
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / immunology
  • Nuclear Proteins
  • Promoter Regions, Genetic
  • Proto-Oncogene Proteins / biosynthesis
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / immunology
  • Tumor Cells, Cultured


  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • DNA, Neoplasm
  • DNA-Binding Proteins
  • MLH1 protein, human
  • Neoplasm Proteins
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • MSH2 protein, human
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein