Programs in Cancer Biology, Gastrointestinal Oncology, and Biostatistics, and Divisions of Human Biology

OBJECTIVES: Most patients with Barrett’s esophagus do not progress to cancer, but those who do seem to have markedly increased survival when cancers are detected at an early stage. Most surveillance programs are based on histological assessment of dysplasia, but dysplasia is subject to observer variation and transient diagnoses of dysplasia increase the cost of medical care. We have previously validated flow cytometric increased 4N fractions and aneuploidy as pre-dictors of progression to cancer in Barrett’s esophagus. However, multiple somatic genetic lesions develop during neoplastic progression in Barrett’s esophagus, and it is likely that a panel of objective biomarkers will be required to manage the cancer risk optimally. METHODS: We prospectively evaluated endoscopic biopsies from 325 patients with Barrett’s esophagus, 269 of whom had one or more follow-up endoscopies, by a robust plat-form for loss of heterozygosity (LOH) analysis, using base-line 17p (p53) LOH as a predictor and increased 4N, aneu-ploidy, high-grade dysplasia, and esophageal adenocarcinoma as outcomes. RESULTS: The prevalence of 17p (p53) LOH at baseline increased from 6 % in negative for dysplasia to 57 % in high-grade dysplasia (p 0.001). Patients with 17p (p53) LOH had increased rates of progression to cancer (relative risk [RR] 16, p 0.001), high-grade dysplasia (R