title: Prognostic implication of the CpG island methylator phenotype in colorectal cancers depends on tumour location.
abstract: BACKGROUND
  Colorectal cancer (CRC) is usually categorised as proximal or distal CRC. Recently, many researchers have tried to determine the molecular heterogeneity of CRCs along bowel subsites. However, the differential effects of the CpG island methylator phenotype (CIMP) and microsatellite instability (MSI) on the clinical outcome according to tumour location are not well-known.
  
  
  METHODS
  We analysed clinicopathologic and molecular characteristics, including CIMP, MSI, KRAS and BRAF mutations, in 734 CRCs according to bowel subsites. And the prognostic value of CIMP and MSI was analysed according to tumour location.
  
  
  RESULTS
  We found a linear increase of female predominance, T, N category, stage, differentiation, absence of luminal necrosis, tumour -infiltrating lymphocytes, Crohn's-like lymphoid reaction, serration and mucin production from the rectum to caecum. CpG island methylator phenotype -high and MSI-high gradually increased from the rectum to caecum. CpG island methylator phenotype is a poor prognostic factor of overall survival (hazard ratio (HR): 4.13, 95% confidence interval (CI): 1.27-13.46) and disease-free survival (HR: 2.90, 95% CI: 1.04-8.08) in rectal cancers.
  
  
  CONCLUSIONS
  Clinicopathologic and molecular profiles of CRCs gradually change along bowel subsites, and the prognostic implication of CIMP is different according to tumour location.
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul 110-744, Korea.
authors.forename: J M
authors.initials: JM
authors.lastname: Bae
authors.forename: J H
authors.initials: JH
authors.lastname: Kim
authors.forename: N-Y
authors.initials: NY
authors.lastname: Cho
authors.forename: T-Y
authors.initials: TY
authors.lastname: Kim
authors.forename: G H
authors.initials: GH
authors.lastname: Kang
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D003110:Colonic Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D004273:DNA, Neoplasm / Q000378:metabolism*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D016246:Lymphocytes, Tumor-Infiltrating / Q000473:pathology; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D010641:Phenotype; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D012004:Rectal Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology; D012737:Sex Factors; D055815:Young Adult; D018631:ras Proteins / Q000235:genetics
chemical_list: D004273:DNA, Neoplasm; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
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