Immunohistochemistry versus microsatellite instability testing in phenotyping colorectal tumors

J Clin Oncol. 2002 Feb 15;20(4):1043-8. doi: 10.1200/JCO.2002.20.4.1043.


Purpose: To compare microsatellite instability (MSI) testing with immunohistochemical (IHC) detection of hMLH1 and hMSH2 in colorectal cancer.

Patients and methods: Colorectal cancers from 1,144 patients were assessed for DNA mismatch repair deficiency by two methods: MSI testing and IHC detection of hMLH1 and hMSH2 gene products. High-frequency MSI (MSI-H) was defined as more than 30% instability of at least five markers; low-level MSI (MSI-L) was defined as 1% to 29% of loci unstable.

Results: Of 1,144 tumors tested, 818 showed intact expression of hMLH1 and hMSH2. Of these, 680 were microsatellite stable (MSS), 27 were MSI-H, and 111 were MSI-L. In all, 228 tumors showed absence of hMLH1 expression and 98 showed absence of hMSH2 expression: all were MSI-H.

Conclusion: IHC in colorectal tumors for protein products hMLH1 and hMSH2 provides a rapid, cost-effective, sensitive (92.3%), and extremely specific (100%) method for screening for DNA mismatch repair defects. The predictive value of normal IHC for an MSS/MSI-L phenotype was 96.7%, and the predictive value of abnormal IHC was 100% for an MSI-H phenotype. Testing strategies must take into account acceptability of missing some cases of MSI-H tumors if only IHC is performed.

Publication types

  • Comparative Study
  • Evaluation Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Base Pair Mismatch / genetics*
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Cost-Benefit Analysis
  • DNA Mutational Analysis
  • DNA Repair
  • DNA, Neoplasm / genetics*
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Microsatellite Repeats / genetics*
  • Middle Aged
  • Phenotype
  • Polymerase Chain Reaction
  • Predictive Value of Tests
  • Sensitivity and Specificity


  • DNA, Neoplasm