Phenotypic attributes and survival in mismatch repair deficient/microsatellite instability-high colorectal carcinomas

BACKGROUND Mismatch repair deficient/microsatellite instability-high (MMR-D/MSI-H) colorectal cancers (CRCs) possess a distinctive genomic profile that results in a spectrum of phenotypic attributes setting them apart from their mismatch repair proficient (MMR-P) or microsatellite stable (MSS) counterparts. CRCs have several prognostic factors, including stage, tumor differentiation, location, lymphovascular and perineural invasion, tumor budding, tumor infiltrating lymphocytes, lymph node yield (LNY), and lymph node ratio (LNR). AIM To determine the unique phenotypic characteristics of MMR-D/MSI-H CRCs and leverage the conventional wisdom of LNY and LNR with the distinctive characteristics of MMR-D/MSI-H CRCs. METHODS This retrospective analysis involved 223 stage I-III CRC patients who underwent surgical resection without neoadjuvant treatment. Clinical and histological features were obtained from patient records and by re-examining the hematoxylin and eosin-stained slides. MMR/MSI status was evaluated for all patients using either MMR immunohistochemistry or MSI testing. RESULTS Of the 223 patients in our study, 87 (39.01%) were MMR-D/MSI-H CRCs while 136 (60.99%) were MMR-P/MSS CRCs. The MMR-D/MSI-H CRCs exhibited significant statistical differences compared to the MMR-P/MSS CRCs in several factors, including location, stage, tumor budding, lymphovascular and perineural invasion, lymphocytic response, LNY, LNR, and size of uninvolved lymph nodes. LNY and LNR were significantly higher in MMR-D/MSI-H group compared with the MMR-P/MSS group (P = 0.003 and P < 0.001, respectively). Also, the interquartile range of the largest uninvolved lymph node was 1 cm (0.8 cm-1.2 cm) in MMR-D/MSI-H CRCs compared to 0.7 cm (0.6 cm-0.97 cm) in MMR-P/MSS CRCs. The overall survival for the MMR-P/MSS CRC group was 71% at five years, and the MMR-D/MSI-H CRC group was 92% at five years (P < 0.001). CONCLUSION MMR-D/MSI-H CRCs possess a unique genomic profile that leads to distinct phenotypic characteristics, including an enhanced immune response. This distinctive profile underscores the substantial prognostic and predictive value of MMR-D/MSI-H status in CRC.