Prognostic and predictive impact of DNA mismatch repair in the management of colorectal cancer

Colorectal cancers develop via two major pathways that include chromosomal instability and microsatellite instability. Microsatellite instability occurs due to deficient DNA mismatch repair (MMR), which can be caused by epigenetic silencing of the MLH1 MMR gene in sporadic colorectal cancers or germline mutations in MMR genes that result in Lynch syndrome. While the molecular origin of deficient MMR differs, sporadic and Lynch syndrome tumors share similar pathological features and have a more favorable stage-adjusted prognosis compared with MMR-proficient cases. While controversy remains, there is evidence to suggest that deficient MMR may predict a lack of benefit from 5-fluorouracil-based adjuvant chemotherapy. The focus of this article is on the MMR phenotype and its prognostic and predictive implications for the management of patients with colorectal cancer.