Open AccessMolecular and prognostic heterogeneity of microsatellite-unstable colorectal cancer
Author(s) -
Tae-You Kim,
Gyeong Hoon Kang
Publication year - 2014
Publication title -
world journal of gastroenterology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.427
H-Index - 155
eISSN - 2219-2840
pISSN - 1007-9327
DOI - 10.3748/wjg.v20.i15.4230
Subject(s) - microsatellite instability , colorectal cancer , mlh1 , dna methylation , biology , epigenetics , cancer research , lymphovascular invasion , cdx2 , methylation , cancer , genetic heterogeneity , dna mismatch repair , oncology , phenotype , medicine , microsatellite , genetics , allele , gene , gene expression , metastasis , homeobox
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, SMAD4 expression, CIMP status and LINE-1 methylation levels.