MMR/MSI for colon cancer

• IHC refers to staining tumor tissue for protein expression of the four MMR genes known to be mutated in LS (MLH1, MSH2, MSH6, and PMS2)
•  A normal IHC test implies that all four MMR proteins are normally expressed (retained).
• Loss (absence) of expression of one or more of the four DNA MMR proteins is often reported as abnormal or positive IHC.
• When IHC is reported as positive, caution should be taken to ensure that positive refers to absence of mismatch expression and not presence of expression.
• Normal is the presence of positive protein staining (retained/intact) and abnormal is negative or loss of staining of protein.
• Loss of protein expression by IHC in any one of the MMR genes guides further genetic testing (mutation detection to the genes where the protein expression is not observed)
• Abnormal MLH1 IHC should be followed by tumor testing for BRAF V600E mutation or MLH1 promoter methylation.
• The presence of BRAF V600E mutation or MLH1 promoter methylation is consistent with sporadic cancer
• However, caution should be exercised in excluding cases from germline screening based on BRAF V600E mutations in the setting of a strong family history