Barrett's esophagus: a model premalignant lesion for adenocarcinoma

Barrett's esophagus is a condition in which the lower esophagus is lined with metaplastic columnar epithelium rather than normal stratified squamous epithelium. It is associated with an increased risk of cancer. Cancers developing in Barrett's epithelium are adenocarcinomas rather than the usual squamous cell esophageal cancers. Barrett's is somewhat unique among premalignant lesions, since it represents an entirely different epithelium from the normal and can therefore be histologically identified with certainty. The abnormal mucosa can be safely accessed repeatedly and its extent quantitated by endoscopy, thereby allowing serial follow-up studies and intervention trials. We are studying Barrett's esophagus as a model premalignant lesion for adenocarcinoma. Ornithine decarboxylase activity was increased in this lesion especially when dysplastic changes were present. Interestingly there was no relationship between polyamine levels and the increased ODC activity. Flow cytometric abnormalities have been demonstrated in Barrett's mucosa. Their significance remains to be determined. Epithelial cells from this lesion have been cultured and characterized. Clonal cytogenetic abnormalities were detected in some specimens. The cultured cells were used to test the effect of drugs on their growth. The ornithine decarboxylase inhibitor, alpha-difluoromethylornithine, significantly inhibited growth even at low concentrations. A clinical intervention trial using 13-cis-retinoic acid has produced no change in the extent of the lesion in 11 evaluable patients. Nevertheless, the successful performance of this clinical study confirms that this lesion can be used for intervention trials aimed at reversing premalignant lesions.