Testing microsatellite instability in solid tumors: the ideal versus what is real

Virgilio Souza E. Silva, Louise De Brot, Rachel P. Riechelmann


The mismatch repair (MMR) genes MLH1, MSH2, MSH6, and PMS2 are responsible for correcting the nucleotide base mispairings and small insertions or deletions that occur during DNA replication. Defects of the MMR system, resulting from mutations in any of the MMR genes, lead to microsatellite instability (MSI) (1), which is observed in approximately 2% to 3% of solid tumors, particularly in metastatic colorectal cancer (mCRC) and other Lynch Syndrome related tumors, such as endometrial carcinoma (2,3). The deficient MMR system results in tumors with a large number of mutations, and consequently the surge of neoantigens and the so-called “immune phenotype”. MMR deficiency is one of the strongest predictive biomarkers of response to treatment with immune checkpoint inhibitors (ICI) (4,5).