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Barrett oesophagus: lessons on its origins from the lesion itself

Nature Reviews Gastroenterology & Hepatology volume 12, pages 50–60 (2015)Cite this article

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Abstract

Barrett oesophagus develops when the lower oesophageal squamous epithelium is replaced with columnar epithelium, which shows both intestinal and gastric differentiation. No consensus has been reached on the origin of Barrett oesophagus. Theories include a direct origin from the oesophageal-stratified squamous epithelium, or by proximal migration of the gastric cardiac epithelium with subsequent intestinalization. Variations of this theory suggest the origin is a distinctive cell at the squamocolumnar junction, the oesophageal gland ducts, or circulating bone-marrow-derived cells. Much of the supporting evidence comes from experimental models and not from studies of Barrett mucosa. In this Perspectives article, we look at the Barrett lesion itself: at its phenotype, its complexity, its clonal architecture and its stem cell organization. We conclude that Barrett glands are unique structures, but share many similarities with gastric glands undergoing the process of intestinal metaplasia. We conclude that current evidence most strongly supports an origin from stem cells in the cardia.

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Figure 1: The structure of a typical Barrett gland.
Figure 2: Phenotypes seen in Barrett epithelium.
Figure 3: Niche succession and gland fission in Barrett oesophagus and intestinal metaplasia of the stomach.
Figure 4: The potential sources of Barrett epithelium.
Figure 5: Morphologic evolution of the glandular phenotype along the length of a Barrett segment.

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Acknowledgements

S.A.C.M. acknowledges funding from CORE, the MRC and Barts Charity. N.A.W. acknowledges funding from Cancer Research UK. M.J. acknowledges funding from the Dutch Cancer Society. The funders had no influence on the design or content of this Perspectives.

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Authors and Affiliations

  1. Centre for Tumour Biology, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, EC1 2AD, UK

    Stuart A. C. McDonald, Danielle Lavery, Nicholas A. Wright & Marnix Jansen

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  1. Stuart A. C. McDonald
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  2. Danielle Lavery
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All authors contributed equally to all aspects of this article.

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Supplementary information

Supplementary Figure 1

Stained Barrett glands. (PDF 231 kb)

Supplementary Figure 2

Intestinal metaplastic glands from the human stomach and Barrett glands are clonal. (PDF 296 kb)

Supplementary Figure 3

a | A large patch of >10 Cytochrome c oxidase (CCO)-deficient Barrett oesophagus glands before laser capture microdissection. (PDF 186 kb)

Supplementary Figure 4

a | (i) A sample of Barrett metaplasia from a patient who has undergone ablative therapy. (PDF 293 kb)

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McDonald, S., Lavery, D., Wright, N. et al. Barrett oesophagus: lessons on its origins from the lesion itself. Nat Rev Gastroenterol Hepatol 12, 50–60 (2015). https://doi.org/10.1038/nrgastro.2014.181

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