Abstract
Has a histologic transition from gastroesophageal reflux disease–damaged epithelium to columnar metaplasia ever been seen in humans? The answer to this question seems to be that it has but that we either do not readily recognize it or it is not readily recognizable with regular light microscopy. There are at least 3 possible mechanisms for the genesis of Barrett esophagus. The first is ulceration at the gastroesophageal junction with subsequent repair by an epithelium that differentiates into Barrett epithelium. The second is metaplasia through multilayered epithelium. The third is creeping columnar metaplasia at the Z-line proximally followed by intestinalization. These 3 hypotheses may not be mutually exclusive, and all may be operative, depending on the local circumstances, amount of inflammation, erosion, ulcers, healing, acid and alkaline reflux, and use of proton pump inhibitors. Any of the epithelial types involved could be stable and not progress. They might even be reversible, which may also in part explain the mosaic of epithelial types that typify Barrett esophagus, and may be modified by any of the molecular mechanisms that turn protein transcription on and off (eg, promoter methylation, mutations). These mechanisms ultimately may also be involved in the genesis of neoplastic transformation.
Multilayered epithelium in a rat model and human Barrett's esophagus: Similar expression patterns of transcription factors and differentiation markers
