Molecular and prognostic heterogeneity of microsatellite-unstable colorectal cancer.
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.
Jung Ho Kim, Department of Pathology, SMG-SNU Boramae Medical Center, Seoul 156-707, South Korea.
Jung Ho
JH
Kim
Jung Ho Kim, Department of Pathology, SMG-SNU Boramae Medical Center, Seoul 156-707, South Korea.
Gyeong Hoon
GH
Kang
D000071616:CDX2 Transcription Factor; D002454:Cell Differentiation; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D018899:CpG Islands; D019175:DNA Methylation; D004260:DNA Repair; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D018095:Germ-Line Mutation; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics; D053842:Microsatellite Instability; D018895:Microsatellite Repeats / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D048493:Proto-Oncogene Proteins B-raf / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras); D051901:Smad4 Protein / Q000378:metabolism; D016896:Treatment Outcome; D018631:ras Proteins / Q000378:metabolism
D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D018398:Homeodomain Proteins; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C497796:SMAD4 protein, human; D051901:Smad4 Protein; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
Adjuvant chemotherapy; Colorectal cancer; CpG islands; DNA methylation; DNA mismatch repair; Microsatellite instability; Prognosis