Identification of histologically distinct conventional adenomas that arise predominately in patients with sessile serrated adenomas

Am J Surg Pathol. 2010 Mar;34(3):355-63. doi: 10.1097/PAS.0b013e3181c6b9dd.

Abstract

We have recently shown that a study population of patients with at least 1 sessile serrated adenoma (SSA) are 4 times more likely to harbor synchronous serrated polyps [SSAs, traditional serrated adenomas (TSAs) and right sided hyperplastic polyps] than a unselected population of patients. However, 35% of the polyps in the study patients were conventional adenomas (CAds). We hypothesized that the CAds in these study patients would have histologic and molecular differences compared with CAds from a control population without sessile serrated adenomas. To this end, 104 study and 79 control CAds were analyzed according to 9 histologic criteria. A subset of these polyps was also screened for BRAF mutations, KRAS mutations, CpG island methylation, and MUC6 expression. A total of 31 study CAds and 2 control CAds had atypical histologic features (bright cytoplasmic eosinophilia +/- focal serrations and crypt dilatation). None of the adenomas tested had mutations in BRAF or KRAS. Evidence of low levels of CpG island methylation was seen in 35% of the atypical CAds and in only 4.5% of the typical CAds. In addition, these atypical CAds were more likely to express MUC6. Thus, the presence of cytoplasmic eosinophilia with or without focal serrations and crypt dilatation identifies a subset of CAds with characteristics of the serrated neoplasia pathway. These atypical CAds occur more commonly in patients predisposed to developing SSAs and suggest the presence of a mucosal field defect in these patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma / chemistry
  • Adenoma / classification
  • Adenoma / genetics
  • Adenoma / pathology*
  • Aged
  • Case-Control Studies
  • Colonic Neoplasms / chemistry
  • Colonic Neoplasms / classification
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / pathology*
  • Colonic Polyps / chemistry
  • Colonic Polyps / classification
  • Colonic Polyps / genetics
  • Colonic Polyps / pathology*
  • CpG Islands
  • DNA Methylation
  • DNA Mutational Analysis
  • Dilatation, Pathologic
  • Eosinophilia / pathology
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Hyperplasia
  • Immunohistochemistry
  • Intestinal Mucosa / pathology
  • Male
  • Middle Aged
  • Mucin-6 / analysis
  • Mutation
  • Precancerous Conditions / chemistry
  • Precancerous Conditions / classification
  • Precancerous Conditions / genetics
  • Precancerous Conditions / pathology*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins / genetics

Substances

  • KRAS protein, human
  • MUC6 protein, human
  • Mucin-6
  • Proto-Oncogene Proteins
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins