Analysis of the premalignant stages of Barrett's oesophagus through to adenocarcinoma by comparative genomic hybridization

Eur J Gastroenterol Hepatol. 2002 Nov;14(11):1179-86. doi: 10.1097/00042737-200211000-00004.


Objectives: Barrett's oesophagus is a pre-neoplastic lesion, which develops as a complication of chronic gastro-oesophageal reflux disease and predisposes the patient to oesophageal adenocarcinoma. Our aim was to characterize karyotypic changes that may occur during the progression of Barrett's metaplasia through low-grade dysplasia and high-grade dysplasia to adenocarcinoma.

Methods: The technique of comparative genomic hybridization was used to characterize genome-wide changes in biopsies from patients with low-grade dysplasia, low-grade dysplasia plus high-grade dysplasia, high-grade dysplasia or adenocarcinoma. Both fresh and archival material was examined.

Results: Comparative genomic hybridization revealed a large amount of widespread chromosome instability at the high-grade dysplasia stage. No significant chromosome changes were detectable by comparative genomic hybridization in patients with low-grade dysplasia. Karyotypic changes in the adenocarcinoma patients were more specific than those found in the high-grade dysplasia patients. Chromosome 4 was amplified most often in high-grade dysplasia and chromosome 8q was amplified most frequently in the adenocarcinomas.

Conclusions: These data demonstrate that high-grade dysplasia is the stage exhibiting widespread chromosome instability, which is detectable by comparative genomic hybridization. This instability is undetectable in low-grade dysplasia. The chromosome variation seen at high-grade dysplasia may be the source of more specific karyotypes that progress to adenocarcinoma. Importantly, we have identified chromosome 4 amplification as being heavily involved in the initiation of Barrett's progression. Specific chromosome changes (4 and 8q) may represent important regions on which to focus attention in future studies, with a view to identifying diagnostic markers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology*
  • Barrett Esophagus / genetics
  • Barrett Esophagus / pathology*
  • Chromosome Mapping
  • DNA Mutational Analysis
  • Esophageal Neoplasms / genetics
  • Esophageal Neoplasms / pathology*
  • Gene Deletion
  • Genetic Predisposition to Disease
  • Humans
  • Neoplasm Staging
  • Nucleic Acid Amplification Techniques
  • Nucleic Acid Hybridization / methods
  • Precancerous Conditions / genetics
  • Precancerous Conditions / pathology*