Accumulation of genetic abnormalities during neoplastic progression in Barrett's esophagus.

Sex chromosome status, ploidy, and proliferation rate were evaluated in archival material of 73 Barrett's esophagus patients (48 males and 25 females). Diagnosis in esophageal mucosa samples ranged from intestinal metaplasia with no dysplasia to invasive esophageal adenocarcinoma; also, four lymph node metastases were studied. Chromosomal and ploidy aberrations were determined by in situ hybridization with repetitive DNA probes specific for chromosomes Y, X, and 1. Proliferation index (Ki-67 protein expression) was assessed by immunohistochemistry. Proliferation rate was elevated in all stages of dysplasia and in the adenocarcinomas. Aneuploidy (hyperdiploidy) and loss of the Y chromosome correlated with the advancing stages toward neoplasia (P < 0.001) and reached high prevalences (70-100%) in high-grade dysplasia and adenocarcinoma. Abnormalities of the X chromosome were not seen. These data suggest that in Barrett's esophagus, genetic perturbations may be generated in relation to a high proliferation rate.