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Methylation patterns define two types of hyperplastic polyp associated with colorectal cancer
  1. C V A Wynter1,
  2. M D Walsh1,
  3. T Higuchi3,
  4. B A Leggett1,
  5. J Young1,
  6. J R Jass2
  1. 1Conjoint Gastroenterology Laboratory, Royal Brisbane and Women’s Hospital Research Foundation, Bancroft Centre, Queensland, Australia
  2. 2Department of Pathology, McGill University, Montreal, Canada
  3. 3Department of Digestive Surgery, Tokyo Medical and Dental University, Tokyo, Japan
  1. Correspondence to:
    Dr C V A Wynter
    Conjoint Gastroenterology Laboratory, Queensland Institute of Medical Research, 300 Herston Rd, Herston Queensland, 4029 Australia;


Aim: Hyperplastic polyps (HP) of the colorectum have traditionally been regarded as non-neoplastic lesions. Recent data implicate HP in the pathogenesis of colorectal cancers (CRC) characterised by extensive DNA methylation and microsatellite instability. The aim of this study was to identify morphological and molecular features that may characterise subtypes of HP with potential for neoplastic progression.

Materials and methods: HP (22) clustering around distal CRC (group I) were compared with HP (58) in subjects with hyperplastic polyposis (group II). DNA methylation was tested in methylated in tumour (MINT) loci (1, 2, 12, 31) and genes HPP1, MGMT, p14ARF, p16INK4a, and hMLH1.

Results: Group II HP showed significantly more methylation than group I HP at all loci except MINT1 and MGMT. Group I showed the lowest frequency of DNA methylation but the highest frequency of K-ras mutation. Group II HP (termed HP variant) had the morphological features of the recently described “sessile serrated adenomas”. Methylation of hMLH1 was found most frequently in group II polyps that included foci of dysplasia (7/10) and in no group I lesions.

Conclusion: The findings support the existence of morphological and molecular heterogeneity among HP and highlight a subset that is likely to have significant malignant potential.

  • hyperplastic polyposis
  • CpG methylation
  • colon cancer
  • microsatellite instability
  • ACF, aberrant crypt foci
  • AD, adenoma
  • CIMP, CpG island methylator phenotype
  • COBRA, combined bisulphite restriction analysis
  • CRC, colorectal cancer
  • HP, hyperplastic polyps
  • HP variant, hyperplastic polyp variant
  • MGMT, O-6-methylguanine DNA methyltransferase
  • MINT, methylated in tumour
  • MP, mixed polyps
  • MSI, microsatellite instability
  • MSI-H, high level MSI
  • MSI-L, low level MSI
  • MSP, methylation specific polymerase chain reaction
  • MSS, microsatellite stable
  • PCR, polymerase chain reaction
  • SA, serrated adenomas
  • VA, villous adenoma

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