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Molecular and prognostic heterogeneity of microsatellite-unstable colorectal cancer Kim JH; Kang GHWorld J Gastroenterol 2014[Apr]; 20 (15): 4230-43Colorectal 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.|*Gene Expression Regulation, Neoplastic[MESH]|*Microsatellite Instability[MESH]|*Mutation[MESH]|CDX2 Transcription Factor[MESH]|Cell Differentiation[MESH]|Colorectal Neoplasms/*genetics/metabolism[MESH]|CpG Islands[MESH]|DNA Methylation[MESH]|DNA Repair[MESH]|Epigenesis, Genetic[MESH]|Germ-Line Mutation[MESH]|Homeodomain Proteins/metabolism[MESH]|Humans[MESH]|Long Interspersed Nucleotide Elements/genetics[MESH]|Microsatellite Repeats/*genetics[MESH]|Phenotype[MESH]|Prognosis[MESH]|Proto-Oncogene Proteins B-raf/metabolism[MESH]|Proto-Oncogene Proteins p21(ras)[MESH]|Proto-Oncogene Proteins/metabolism[MESH]|Smad4 Protein/metabolism[MESH]|Treatment Outcome[MESH]|ras Proteins/metabolism[MESH] |
