Deficient mismatch repair in colorectal cancer: current perspectives on patient management and future directions

摘要

Molecular aberrations leading to colorectal cancer are diverse and heterogeneity exists both at a molecular level and in clinical behavior. Defective mismatch repair (dMMR) is a feature of 15% of colorectal cancers. These are hypermutated tumors, mostly right sided and histopathologically elicit a marked immune response. A proportion of these arise due to germline mutation of a mismatch repair gene giving rise to Lynch syndrome, while the majority arise sporadically due to somatic alteration of the MLH1 mismatch repair gene. Although dMMR is associated with an excellent patient prognosis, as tumor stage advances the frequency of dMMR declines and the association with improved prognosis dissipates. It is apparent that dMMR tumors do not represent a unique molecular subset. As the knowledge of the underlying biology evolves, the hope is for individualized therapy that goes well beyond the crude and oversimplified categorization of dMMR versus proficient MMR.