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J Clin Oncol. 2002 Feb 15;20(4):1043-8.

Immunohistochemistry versus microsatellite instability testing in phenotyping colorectal tumors.

Author information

1
Department of Medical Genetics, Mayo Foundation, Rochester, MN 55905, USA. nlindor@mayo.edu

Abstract

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.

PMID:
11844828
DOI:
10.1200/JCO.2002.20.4.1043
[Indexed for MEDLINE]

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