Gastric Proteins MUC5AC and TFF1 as Potential Diagnostic Markers of Colonic Sessile Serrated Adenomas/Polyps

Am J Clin Pathol. 2016 Nov 1;146(5):530-537. doi: 10.1093/ajcp/aqw142.

Abstract

Objectives: A subset of colon cancers originates from sessile serrated adenomas/polyps (SSA/Ps). Our goal was to identify markers for SSA/Ps that could aid in distinguishing them from hyperplastic polyps (HPs).

Methods: We performed immunostaining for gastric proteins MUC5AC and TFF1 in formalin-fixed, paraffin-embedded (FFPE) samples of HPs (n = 47), SSA/Ps (n = 37), and normal colon (n = 30).

Results: Control mucosa expressed only trace amounts of MUC5AC and TFF1. HPs exhibited an 11.3- and 11.4-fold increase in MUC5AC and TFF1 expression confined to the upper segments of the crypts near the luminal surface of the polyps. SSA/Ps displayed on average 1.6-fold (MUC5AC, P < .008) and 1.4-fold (TFF1, P < .03) higher signal intensity for these markers than HPs, with a dramatic coexpression of MUC5AC and TFF1 typically occupying the entire length of the crypt. Immunoperoxidase results were similar to immunofluorescence staining for both MUC5AC and TFF1.

Conclusions: Our results suggest that the analysis of expression of MUC5AC and TFF1 may be useful for differentiating SSA/Ps from HPs. We also suggest the possibility that crypt morphology may be at least partly due to overproduction of highly viscous gastric mucins and that these proteins may play a role in the serrated pathway to colon carcinogenesis.

Keywords: Colon cancer; Hyperplastic polyps; MUC5AC; Serrated polyps; Sessile serrated adenomas/polyps; TFF1.

MeSH terms

  • Adenoma / diagnosis*
  • Adenoma / metabolism
  • Adenoma / pathology
  • Biomarkers, Tumor / analysis*
  • Colon / metabolism
  • Colon / pathology
  • Colonic Neoplasms / diagnosis*
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • Colonic Polyps / diagnosis*
  • Colonic Polyps / metabolism
  • Colonic Polyps / pathology
  • Diagnosis, Differential
  • Humans
  • Hyperplasia / diagnosis
  • Hyperplasia / metabolism
  • Hyperplasia / pathology
  • Immunohistochemistry
  • Mucin 5AC / analysis*
  • Trefoil Factor-1 / analysis*

Substances

  • Biomarkers, Tumor
  • MUC5AC protein, human
  • Mucin 5AC
  • TFF1 protein, human
  • Trefoil Factor-1