Serrated polyposis syndrome: molecular, pathological and clinical aspects

World J Gastroenterol. 2012 May 28;18(20):2452-61. doi: 10.3748/wjg.v18.i20.2452.

Abstract

Hyperplastic polyps have traditionally been considered not to have malignant potential. New pathological classification of serrated polyps and recent discoveries about the serrated pathway of carcinogenesis have revolutionized the concepts and revitalized the research in this area. Until recently, it has been thought that most colorectal cancers arise from conventional adenomas via the traditional tumor suppressor pathway initiated by a mutation of the APC gene, but it has been found that this pathway accounts for only approximately 70%-80% of colorectal cancer (CRC) cases. The majority of the remaining colorectal cancer cases follow an alternative pathway leading to CpG island methylator phenotype carcinoma with BRAF mutation and with or without microsatellite instability. The mechanism of carcinomas arising from this alternative pathway seems to begin with an activating mutation of the BRAF oncogene. Serrated polyposis syndrome is a relatively rare condition characterized by multiple and/or large serrated polyps of the colon. Clinical characteristics, etiology and relationship of serrated polyposis syndrome to CRC have not been clarified yet. Patients with this syndrome show a high risk of CRC and both sporadic and hereditary cases have been described. Clinical criteria have been used for diagnosis and frequent colonoscopy surveillance should be performed in order to prevent colorectal cancer. In this review, we try to gather new insights into the molecular pathogenesis of serrated polyps in order to understand their possible clinical implications and to make an approach to the management of this syndrome.

Keywords: Colorectal cancer; CpG island methylator phenotype; Hyperplastic polyps; Serrated pathway; Serrated polyposis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / pathology*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology*
  • CpG Islands / genetics
  • Humans
  • Intestinal Polyposis / genetics
  • Intestinal Polyposis / pathology*
  • Methylation
  • Proto-Oncogene Proteins B-raf / genetics*

Substances

  • Proto-Oncogene Proteins B-raf