Goblet cells in Barrett’s oesophagus: cancer precursor, risk marker, or irrelevance?

It is popularly held that cancer risk in Barrett's oesophagus is conferred by intestinal metaplasia (IM), defined by goblet cells. This belief is difficult to test, partly because it is impossible to prove an absence of goblet cells in a particular oesophagus: no matter how many biopsies without them have been examined, it is always possible there may be some in the very next biopsy.Also, little is known about the spatial distribution and temporal drift of the intestinal phenotype in Barrett's oesophagus; and ignorance of relationships between duration, extent and phenotypic diversity in a Barrett segment on the one hand, and dysplasia and its progression on the other is a problem.Cancer-related genetic and epigenetic abnormalities in non-intestinal glandular mucosa further call in question the belief that intestinalized mucosa alone is at increased risk of malignancy.Accurate determination of patient-specific cancer risk in Barrett's oesophagus will require more sophisticated understanding of how mucosal phenotype is determined (cell fate specification) and how dysplasia evolves than presently available, and is unlikely to be reducible to whether intestinal metaplasia is ‘present’ or ‘absent’. That intestinal metaplasia is a necessary precondition for Barrett's adenocarcinoma is a dogma hindering understanding of carcinogenesis in metaplastic oesophageal mucosa and at the oesophago-gastric junction, and has no value in the definition of Barrett's oesophagus.