Anti-p53 antibodies in patients with Barrett's esophagus or esophageal carcinoma can predate cancer diagnosis

Background and Aims: We previously discovered anti-p53 antibodies predating a cancer diagnosis in subjects at increased risk for liver, lung, breast, and prostate cancer. Recently, we reported a significant correlation (P < 0.017) between p53 antibodies and p53 mutations in patients with late- stage esophageal carcinoma. Because others have reported p53 mutations and overexpression of p53 protein in Barrett's esophagus, we studied p53 antibodies in plasma of 88 serially endoscoped patients: 36 with Barrett's metaplasia, 23 with esophageal squamous cell carcinoma, 10 with esophageal adenocarcinoma, and 19 with esophagitis or normal esophagus. Methods: We used enzyme immunoassay, immunoblotting, and immunoprecipitation assays for p53 antibodies; polymerase chain reaction, denaturant gradient gel electrophoresis, and sequencing for p53 mutations; and immunohistochemistry for p53 protein. Results: p53 antibodies were detected in 4 patients with Barrett's esophagus, including 1 with dysplasia that later progressed to adenocarcinoma, and in 10 cancer patients (P = 0.002) (8 squamous and 2 adenocarcinoma), 2 of whom (1 squamous, 1 adenocarcinoma) had antibodies before cancer was diagnosed. Other patient groups were too small for informative statistical analysis. Six antibody-positive cancer patients had p53 mutations, whereas 2 patients with cancer and 1 with Barrett's esophagus with antibodies had p53 protein overexpressed in esophageal tissues. Conclusions: Patients with Barrett's esophagus and esophageal cancer can develop p53 antibodies that may predate the clinical diagnosis of malignancy.