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Prognostic implications of CpG island hypermethylator phenotype in colorectal cancers

Cited 106 time in Web of Science Cited 112 time in Scopus
Authors
Kim, Jung Ho; Shin, So Hyun; Kwon, Hyeong Ju; Cho, Nam Yun; Kang, Gyeong Hoon
Issue Date
2009-12
Publisher
SPRINGER
Citation
VIRCHOWS ARCHIV; Vol.455 6; 485-494
Keywords
Colon cancerMicrosatellite instabilityCpG island methylator phenotypeDNA methylation
Abstract
CpG island methylator phenotype (CIMP) refers to a subset of colorectal cancers (CRCs) that are characterized by concordant hypermethylation of multiple CpG island loci. CIMP+ CRCs have peculiar clinicopathological features. However, controversy exists over prognostic implications of CIMP in CRCs. We analyzed 320 cases of CRCs for their CIMP status using the MethyLight assay and determined clinicopathological features and prognostic implications of CIMP alone or in combination with microsatellite instability (MSI). With methylation of five or more markers among eight markers examined, CIMP+ tumors were significantly associated with female gender, proximal tumor location, poor differentiation, nodal metastasis, more advanced cancer, BRAF mutations, MSI, and poor prognosis (all P values < 0.05). Ogino`s combined eight-marker panel outperformed the Ogino and the Laird five-marker panels in detecting these features. Of the four molecular subtypes generated by the combination of CIMP and MSI status, the CIMP+/MSI- subtype showed the worst clinical outcome (P = 0.0003). However, poor prognosis of CIMP+/MSI- subtype was found to be attributed to BRAF mutation. In conclusion, the CIMP+/MSI- subtype tends to present with distinct clinicopathological and molecular features and shows the worst clinical outcome among the four molecular subtypes of CRCs.
ISSN
0945-6317
Language
English
URI
https://hdl.handle.net/10371/76609
DOI
https://doi.org/10.1007/s00428-009-0857-0
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College of Medicine/School of Medicine (의과대학/대학원)Pathology (병리학전공)Journal Papers (저널논문_병리학전공)
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