Clinicopathological features of CpG island methylator phenotype-positive colorectal cancer and its adverse prognosis in relation to KRAS/BRAF mutation

Sun Lee, Nam Yun Cho, Minhee Choi, Eun J. Yoo, Jung Ho Kim, Gyeong H. Kang

Research output: Contribution to journalArticlepeer-review

137 Citations (Scopus)

Abstract

CpG island methylator phenotype (CIMP) is a recently described subset of colorectal cancers (CRC) with widespread methylation of multiple promoter CpG islands. But the prognostic implication of CIMP in CRC has not been clarified. Thus, the aim of the present study was to differentiate the unique characteristics of CIMP from those of microsatellite instability (MSI)-high CRC, especially with regard to prognosis. CIMP, MSI, and mutations of KRAS codons 12 and 13 and of BRAF codon 600 were evaluated in 134 sporadic CRC. Patient survival and other clinicopathological variables were correlated with CIMP or genetic changes. High CIMP, high MSI, and mutations in KRAS or BRAF were detected in 31.3%, 14.2%, 33.6%, and 4.5% of overall CRC, respectively. High CIMP was closely associated with MSI and BRAF mutation but not with KRAS mutation. CIMP-high, microsatellite-stable (MSS) CRC were significantly associated with proximal location and nodal metastasis and had close but non-significant associations with liver metastasis. A worse clinical outcome was found for CIMP-high, MSS CRC with KRAS/BRAF mutation but not for those lacking KRAS/BRAF mutation. The findings support the contention that CIMP-high CRC have distinct clinicopathological and epidemiological features and suggest that the alleged poor clinical outcome of CIMP-high CRC patients is closely associated with the presence of KRAS/BRAF mutation.

Original languageEnglish
Pages (from-to)104-113
Number of pages10
JournalPathology International
Volume58
Issue number2
DOIs
Publication statusPublished - Feb 2008

Keywords

  • BRAF
  • Colorectal cancer
  • CpG islands
  • DNA methylation
  • KRAS
  • Microsatellite instability

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