ANTI-P53 ANTIBODIES IN PATIENTS WITH BARRETTS-ESOPHAGUS OR ESOPHAGEAL-CARCINOMA CAN PREDATE CANCER-DIAGNOSIS

Background & Aims: We previously discovered anti-p53 antibodies predat ing a cancer diagnosis in subjects at increased risk for liver, lung, breast, and prostate cancer. Recently, we reported a significant corre lation (P < 0.017) between p53 antibodies and p53 mutations in patient s with late-stage esophageal carcinoma. Because others have reported p 53 mutations and overexpression of p53 protein in Barrett's esophagus, we studied p53 antibodies in plasma of 88 serially endoscoped patient s: 36 with Barrett's metaplasia, 23 with esophageal squamous cell carc inoma, 10 with esophageal adenocarcinoma, and 19 with esophagitis or n ormal esophagus. Methods: We used enzyme immunoassay, immunoblotting, and immunoprecipitation assays for p53 antibodies; polymerase chain re action, denaturant gradient gel electrophoresis, and sequencing for p5 3 mutations; and immunohistochemistry for p53 protein. Results: p53 an tibodies were detected in 4 patients with Barrett's esophagus, includi ng 1 with dysplasia that later progressed to adenocarcinoma, and in 10 cancer patients (P 0.002) (8 squamous and 2 adenocarcinoma), 2 of who m (1 squamous, 1 adenocarcinoma) had antibodies before cancer was diag nosed. Other patient groups were too small for informative statistical analysis. Six antibody-positive cancer patients had p53 mutations, wh ereas 2 patients with cancer and 1 with Barrett's esophagus with antib odies 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.