Evolution of oesophageal adenocarcinoma from metaplastic columnar epithelium without goblet cells in Barrett's oesophagus

Gut. 2016 Jun;65(6):907-13. doi: 10.1136/gutjnl-2015-310748. Epub 2015 Dec 23.


Objective: Barrett's oesophagus commonly presents as a patchwork of columnar metaplasia with and without goblet cells in the distal oesophagus. The presence of metaplastic columnar epithelium with goblet cells on oesophageal biopsy is a marker of cancer progression risk, but it is unclear whether clonal expansion and progression in Barrett's oesophagus is exclusive to columnar epithelium with goblet cells.

Design: We developed a novel method to trace the clonal ancestry of an oesophageal adenocarcinoma across an entire Barrett's segment. Clonal expansions in Barrett's mucosa were identified using cytochrome c oxidase enzyme histochemistry. Somatic mutations were identified through mitochondrial DNA sequencing and single gland whole exome sequencing.

Results: By tracing the clonal origin of an oesophageal adenocarcinoma across an entire Barrett's segment through a combination of histopathological spatial mapping and clonal ordering, we find that this cancer developed from a premalignant clonal expansion in non-dysplastic ('cardia-type') columnar metaplasia without goblet cells.

Conclusion: Our data demonstrate the premalignant potential of metaplastic columnar epithelium without goblet cells in the context of Barrett's oesophagus.


Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / pathology*
  • Barrett Esophagus / complications*
  • Biopsy
  • Electron Transport Complex IV
  • Epithelium / pathology
  • Esophageal Neoplasms / pathology*
  • Exome
  • Female
  • Goblet Cells / pathology*
  • Humans
  • Metaplasia / pathology
  • Middle Aged
  • Mitochondria
  • Mutation
  • Sequence Analysis, DNA


  • Electron Transport Complex IV

Supplementary concepts

  • Adenocarcinoma Of Esophagus