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

Academic Article

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.
  • Keywords

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

    Author List

  • Pai RK; Mackinnon AC; Joseph L; Noffsinger A; Hart J
  • Start Page

  • 355
  • End Page

  • 363
  • Volume

  • 34
  • Issue

  • 3