A Comprehensive Study of Microsatellite Instability Testing And Its Comparison With Immunohistochemistry In Gastric And Colorectal Cancers

Abstract Background Microsatellite instability (MSI) testing was comprehensively analyzed and compared with immunohistochemistry (IHC) for the mismatch repair (MMR) protein in gastric cancer (GC) and colorectal cancer (CRC). Methods PCR-based MSI testing was performed to compare the tumor and non-neoplastic normal tissues using five microsatellites consisting of two mononucleotide (BAT-26, BAT-25) and three dinucleotide (D5S346, D2S123, and D17S250) in 5,676 GC and 2,553 CRC cases. IHC for the MMR protein MLH1 was done in GCs, and IHC for four MMR proteins (MLH1, MSH2, MSH6, and PMS2) was performed in CRCs. Reviews were carried out for discordant or indeterminate IHC cases (such as focal loss of expression, equivocal expression, or abnormal expression patterns). Results MSI-high (MSI-H) and MMR-deficient (dMMR) expression was observed in 521 (9.2%) GC and 171 (6.7%) CRC cases. Discordance between MSI testing and IHC as well as indeterminate IHC cases accounted for 54 (0.9%) and 29 (1.1%) cases out of all GC and CRC cases, respectively, but accounted for 9.4% and 14.1% out of 575 GC and 205 CRC cases, respectively, excluding unequivocal microsatellite stable/MSI-low and MMR-proficient (pMMR) expression cases. pMMR expression was observed in most of the MSI-H GCs and CRCs consisting of only one unstable BAT-25 mononucleotide marker or solely of dinucleotide markers. ConclusionsConsidering the low incidence of MSI-H or dMMR expression, discordant or indeterminate IHC and/or MSI results were occasionally identified in GC and CRC cases, requiring complementary testing. These findings provide evidence for MSI testing and MMR IHC in routine clinical practice.