Immunohistochemistry for MSH2 and MHL1: a method for identifying mismatch repair deficient colorectal cancer

Colorectal cancers with DNA mismatch repair (MMR) gene mutations characteri stically display a high rate of replication errors in simple repetitive seq uences detectable as microsatellite instability (MSI). Most are the result of somatic MMR dysfunction; however, a subset are caused by germline mutati ons. The availability of commercial antibodies for MSH1 and MLH2 offers an alternative strategy to molecular methods for identifying MMR deficient can cers. To evaluate immunohistochemistry, MLH1 and MSH2 expression was studie d using monoclonal antibodies in formalin fixed, paraffin wax embedded canc ers. The immunohistochemical staining patterns of 23 cancers displaying MSI , including four cases with germline mutations, were compared with 23 micro satellite stable (MSS) cancers. All MSS cancers exhibited staining with bot h antibodies. Twenty two of the MSI cases showed absent MMR expression with either anti-MSH1 or anti-MLH2. The high sensitivity and predictive value o f immunohistochemistry in detecting MMR deficiency offers a method of discr iminating between MSI and MSS cancers caused by MSH1 and MLH2 dysfunction. The application and suitability of immunohistochemistry for the detection o f MSI and as a strategy for prioritising the mutational analysis of MMR gen es in routine clinical practice is discussed.