Barrett's esophagus, dysplasia, and adenocarcinoma

Abstract

In Barrett's esophagus the normal stratified squamous epithelium lining the esophagus becomes replaced by metaplastic columnar epithelium containing goblet cells; it develops as a complication of chronic gastroesophageal reflux disease and predisposes the patient to adenocarcinoma. The frequency with which it leads to adenocarcinoma is not established with certainty, but the reported prevalence averages approximately 10% when the diagnosis of Barrett's esophagus is first made. The estimated incidence of adenocarcinoma varies from one in 152 to one in 441 cases per patient year, or a 30- to 125-fold excess risk. Esophageal adenocarcinoma arises only in patients with metaplastic columnar epithelium. Dysplasia precedes adenocarcinoma in Barrett's esophagus and arises from the metaplastic epithelium; it has been proposed as a marker for detecting patients at high risk for developing carcinoma. Problems with the use of dysplasia as a marker for cancer risk include difficulty in differentiating it from reactive change, variability in diagnosis and grading between observers and when the same observer interprets the sections on different occasions, and lack of understanding of its natural history. Methods other than dysplasia for detecting patients at highest risk for developing carcinoma have been sought, but flow cytometric analysis of DNA content is the only one proven to be valuable to date. Flow cytometric abnormalities correlate well with histological progression in Barrett's esophagus. The prevalence of elevated S phase and G 2/tetraploid fractions and of aneuploid cell populations increases with histological progression from metaplasia to indefinite/low grade dysplasia to high grade dysplasia and cancer. Flow cytometric abnormalities in endoscopic biopsy specimens identify those patients with a higher risk of progression to high grade dysplasia or adenocarcinoma.