Reduced expression of αGlcNAc in Barrett's oesophagus adjacent to Barrett's adenocarcinoma--a possible biomarker to predict the malignant potential of Barrett's oesophagus

Histopathology. 2014 Mar;64(4):536-46. doi: 10.1111/his.12296. Epub 2013 Nov 23.

Abstract

Aims: Gastric gland mucin contains O-glycans exhibiting terminal α1,4-linked N-acetylglucosamine residues (αGlcNAc). Recently we demonstrated that mice deficient in αGlcNAc in gastric gland mucin develop gastric adenocarcinoma spontaneously, indicating that αGlcNAc is a tumour suppressor for gastric cancer. However, the role of αGlcNAc in Barrett's oesophagus (BO) remains unknown. In this study, we investigated whether reduced αGlcNAc expression in BO is associated with development of Barrett's adenocarcinoma (BAC).

Methods and results: Thirty-five BO lesions adjacent to BAC were examined by immunohistochemistry for αGlcNAc, MUC6 and CDX2. As controls, 35 BO lesions without BAC obtained from patients with oesophageal squamous cell carcinoma were also analysed. Expression of αGlcNAc relative to its scaffold MUC6 in BO adjacent to BAC was reduced significantly compared to control BO. Decreased αGlcNAc expression in BO adjacent to BAC was particularly significant in patients with smaller tumour size (<20 mm) and minimal invasion of tumour cells to the superficial muscularis mucosae. There was also a significant inverse correlation between αGlcNAc and CDX2 expression in BO adjacent to BAC.

Conclusions: Decreased expression of αGlcNAc compared with MUC6 in BO is a possible hallmark in predicting BAC development.

Keywords: Barrett's adenocarcinoma; O-glycan; immunohistochemistry; mucin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylglucosamine / metabolism*
  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology*
  • Aged
  • Aged, 80 and over
  • Animals
  • Barrett Esophagus / metabolism*
  • Barrett Esophagus / pathology*
  • Biomarkers, Tumor / metabolism
  • CDX2 Transcription Factor
  • Case-Control Studies
  • Disease Progression
  • Esophageal Neoplasms / metabolism*
  • Esophageal Neoplasms / pathology*
  • Female
  • Homeodomain Proteins / metabolism
  • Humans
  • Immunohistochemistry
  • Male
  • Mice
  • Middle Aged
  • Mucin-6 / metabolism
  • Polysaccharides / metabolism

Substances

  • Biomarkers, Tumor
  • CDX2 Transcription Factor
  • CDX2 protein, human
  • Homeodomain Proteins
  • MUC6 protein, human
  • Mucin-6
  • Polysaccharides
  • Acetylglucosamine

Supplementary concepts

  • Adenocarcinoma Of Esophagus