From:  Resistance to immune checkpoint inhibitors in colorectal cancer with deficient mismatch repair/microsatellite instability: misdiagnosis, pseudoprogression and/or tumor heterogeneity?

Methods for dMMR/MSI testing

MethodCharacteristics
Immunohistochemistry (IHC)

  • Detects loss of expression of MMR proteins in tumor specimens

  • Uses antibodies directed against MLH1, PMS2, MSH2, MSH6

  • Staining pattern useful for screening of the Lynch syndrome

Polymerase chain reaction (PCR)

  • Detects the altered length of microsatellite loci as consequence of functional failure of MMR proteins

  • Available reference panels use different mononucleotide and/or dinucleotide markers

  • Usually, an MSI phenotype is defined by the presence of at least two unstable markers compared with healthy tissue or at least three unstable markers in the absence of healthy tissue

Next generation sequencing (NGS)

  • MSI usually determined by analyzing a large number of DNA markers

  • Less standardized as compared with IHC and PCR

Return to article view

MMR: mismatch repair; dMMR: deficient MMR; MLH1: mutL homologue 1; PMS2: postmeiotic segregation increased 2; MSH2: mutS homologue 2; MSI: microsatellite instability; IHC: immunohistochemistry