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Immunohistochemistry for MSH2 and MHL1: a method for identifying mismatch repair deficient colorectal cancer
  1. J G Stone1,
  2. D Robertson2,
  3. R S Houlston1
  1. 1Section of Cancer Genetics, Institute of Cancer Genetics, Sutton, Surrey SM2
  2. 2Section of Cell Biology and Experimental Pathology, Institute of Cancer Genetics
  1. Dr Houlston r.houlston{at}


Colorectal cancers with DNA mismatch repair (MMR) gene mutations characteristically display a high rate of replication errors in simple repetitive sequences detectable as microsatellite instability (MSI). Most are the result of somatic MMR dysfunction; however, a subset are caused by germline mutations. The availability of commercial antibodies for MSH1 and MLH2 offers an alternative strategy to molecular methods for identifying MMR deficient cancers. To evaluate immunohistochemistry, MLH1 and MSH2 expression was studied using monoclonal antibodies in formalin fixed, paraffin wax embedded cancers. The immunohistochemical staining patterns of 23 cancers displaying MSI, including four cases with germline mutations, were compared with 23 microsatellite stable (MSS) cancers. All MSS cancers exhibited staining with both antibodies. Twenty two of the MSI cases showed absent MMR expression with either anti-MSH1 or anti-MLH2. The high sensitivity and predictive value of immunohistochemistry in detecting MMR deficiency offers a method of discriminating between MSI and MSS cancers caused by MSH1 and MLH2 dysfunction. The application and suitability of immunohistochemistry for the detection of MSI and as a strategy for prioritising the mutational analysis of MMR genes in routine clinical practice is discussed.

  • colorectal cancer
  • mismatch repair
  • MSH2
  • MLH1
  • hereditary non-polyposis colorectal cancer
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  • Correction

    In the text the MSH2 and MLH1 genes were sometimes mistakenly written as MSH1 and MHL2, respectively. The authors apologise for this error.


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