Update on the serrated pathway to colorectal carcinoma

Hum Pathol. 2011 Jan;42(1):1-10. doi: 10.1016/j.humpath.2010.06.002. Epub 2010 Sep 24.


Adenocarcinoma of the large intestine can no longer be considered one disease but rather a family of diseases with different precursor lesions, different molecular pathways, and different end-stage carcinomas with varying prognoses. Approximately 60% of colorectal carcinomas arise from conventional adenomas via the suppressor pathway leading to microsatellite stable carcinomas. These carcinomas represent the pathway that has been the target of screening and prevention programs to date. However, approximately 35% of carcinomas arise along the serrated pathway developing from the precursor lesion known as the sessile serrated adenoma (also referred to as the sessile serrated polyp). Sessile serrated adenomas/polyps lead to carcinomas with extensive CpG island promoter methylation (CpG island methylated phenotype positive carcinomas), which can be either microsatellite instable high or microsatellite stable. The remaining 5% of carcinomas arise from conventional adenomas in patients with germ line mutations of mismatch repair genes (Lynch syndrome), leading to CpG island methylated phenotype negative microsatellite instable carcinomas. Carcinomas arising from sessile serrated adenomas/polyps are not prevented by removing conventional adenomas and hence may be missed in routine screening programs. In addition, a subset of these lesions may potentially progress rapidly to carcinoma; hence, it is likely that these lesions will require a different screening strategy from that used for conventional adenomas. This article reviews the various pathways to colorectal carcinoma with emphasis on the serrated pathway and evaluates the implications of this pathway for colorectal carcinomas screening programs.

Publication types

  • Review

MeSH terms

  • Adenocarcinoma / pathology
  • Adenoma / genetics
  • Adenoma / pathology
  • Colonic Polyps / genetics
  • Colonic Polyps / pathology
  • Colorectal Neoplasms / etiology*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology*
  • CpG Islands
  • Humans
  • Precancerous Conditions / pathology