Molecular and prognostic heterogeneity of microsatellite-unstable colorectal cancer

摘要

Colorectal cancers(CRCs)with a high level of microsatellite instability(MSI-H)are clinicopathologically distinct tumors characterized by predominance in females,proximal colonic localization,poor differentiation,mucinous histology,tumor-infiltrating lymphocytes,a Crohn’s-like lymphoid reaction and a favorable prognosis.In terms of their molecular features,MSI-H CRCs are heterogeneous tumors associated with various genetic and epigenetic alterations,including DNA mismatch repair deficiency,target microsatellite mutations,BRAF mutations,a CpG island methylator phenotype-high(CIMP-H)status,and a low level of genomic hypomethylation.The molecular heterogeneity of MSI-H CRCs also depends on ethnic differences;for example,in Eastern Asian countries,relatively low frequencies of CIMP-H and BRAF mutations have been observed in MSI-H CRCs compared to Western countries.Although the prognostic features of MSI-H CRCs include a favorable survival of patients and low benefit of adjuvant chemotherapy,there may be prognostic differences based on the molecular heterogeneity of MSI-H CRCs.Here,we have reviewed and discussed the molecular and prognostic features of MSI-H CRCs,as well as several putative prognostic or predictive molecular markers,including HSP110 expression,beta2-microglobulin mutations,myosin 1a expression,CDX2/CK20 expression,SMAD4expression,CIMP status and LINE-1 methylation levels.