Microsatellite instability (MSI) is reflective of a deficient mismatch repair (dMMR) system, which is mostly associated with the methylation of mismatch repair (MMR) genes and BRAF mutations in sporadic colorectal cancers (CRCs). We performed a retrospective study to analyze the clinicopathological features of dMMR CRCs and their association with the BRAF V600E mutation. The incidence of dMMR CRCs in our cohort was 7.4 % (118/1603). Immunohistochemistry (IHC) revealed four common dMMR IHC patterns in 116 dMMR CRCs from 110 patients. dMMR type 1 (MLH1-/PMS2-) CRCs were the most frequent pattern, usually showing typical proximal location and MSI histology. The BRAF V600E mutation was almost exclusively observed in dMMR type 1 (32 of 72) and dMMR type 2 (PMS- only, 7 of 18) CRCs (p = 0.001). Patients with dMMR type 3 (MSH2-/MSH6-) CRCs were usually diagnosed at younger ages (p < 0.001) and had the strongest family history of Lynch syndrome-associated tumors (p = 0.002). dMMR type 3 CRCs frequently presented at advanced stages (p = 0.005) with perineural invasion (p = 0.021). We also found a significant positive association of dMMR type 1 and type 3 with advanced stages of CRC, whereas dMMR types 2 and 4 (MSH6- only) were usually diagnosed at early stages of CRC (p < 0.001). In conclusion, BRAF V600E mutations almost exclusively occurred in dMMR type 1 and 2 CRCs. Patterns of MMR protein expression display distinct associations with tumor staging and age at diagnosis.
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