Colorectal serrated adenocarcinoma

Histopathology. 2007 Jan;50(1):131-50. doi: 10.1111/j.1365-2559.2006.02548.x.


Colorectal cancer (CRC) ranks among the three most common cancers in terms of both cancer incidence and cancer-related deaths in most Western countries. Serrated adenocarcinoma is a recently described, distinct variant of CRC, accounting for about 7.5% of all CRCs and up to 17.5% of most proximal CRCs. It has been postulated that about 10-15% of sporadic CRCs would have their origin in serrated polyps that harbour a significant malignant potential. These lesions include hyperplastic-type aberrant crypt foci, hyperplastic polyps, sessile serrated adenomas, admixed polyps and serrated adenomas, and constitute the so-called 'serrated pathway', which is distinct from both the conventional adenoma-carcinoma pathway and the mutator pathway of hereditary non-polyposis CRC and is characterized by early involvement of oncogenic BRAF mutations, excess CpG island methylation (CIM) and subsequent low- or high-level DNA microsatellite instability (MSI). Methylation of hMLH1 is likely to explain the increased frequency of high-level MSI (16%) and methylation of MGMT is postulated to explain the low-level MSI (29%) in serrated adenocarcinomas. Reproducible histopathological criteria for serrated adenocarcinoma have recently been established and they have been qualified by DNA expression analysis for 7928 genes, showing clustering of serrated adenocarcinomas into a molecular entity apart from conventional adenocarcinoma, and representing with distinct down-regulation of EPHB2, PTCH and up-regulation of HIF1alpha.

Publication types

  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology*
  • Adenoma / genetics
  • Adenoma / pathology*
  • Carrier Proteins / genetics
  • Colonic Polyps / genetics
  • Colonic Polyps / pathology*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology*
  • CpG Islands
  • DNA Methylation
  • DNA Modification Methylases
  • DNA Repair Enzymes
  • Humans
  • Microsatellite Instability
  • MutL Protein Homolog 1
  • Mutation
  • Nuclear Proteins / genetics
  • Precancerous Conditions / genetics
  • Precancerous Conditions / pathology
  • Proto-Oncogene Proteins B-raf / genetics
  • Tumor Suppressor Protein p14ARF / genetics
  • Tumor Suppressor Proteins


  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • MLH1 protein, human
  • Nuclear Proteins
  • Tumor Suppressor Protein p14ARF
  • Tumor Suppressor Proteins
  • DNA Modification Methylases
  • MGMT protein, human
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • MutL Protein Homolog 1
  • DNA Repair Enzymes