Early Diagnosis of Columnar Metaplasia at the Esophagogastric Junction (EGJ) Using a Monoclonal Antibody and Its Reversibility with Proton-Pump Inhibitor (PPI) Therapy

Abstract

Purpose: Barrett's esophagus (BE) is a known pre-malignant complication of gastroesophageal reflux disease (GERD), and once developed, it is resistant to PPI therapy. A biomarker that might help early diagnosis of metaplasia and allow early initiation of chemoprevention is very much needed. We developed a novel monoclonal antibody, mAb Das-1, that reacts to BE with 100% sensitivity and specificity. It does not react with normal esophagus, EGJ and stomach epithelium. With the use of mAb Das-1, we examined the reversibility of the metaplastic process with PPI therapy. Methods: We have prospectively followed up to 2 years a cohort of 12 patients with GERD who, at initial endoscopic biopsy, showed positive reactivity with mAb Das-1. All patients were treated with PPI. Histological and phenotypic changes on yearly follow-up endoscopy were examined using formalin fixed specimens from the EGJ biopsy tissue. mAb Das-1 reactivity was detected by a sensitive immunoperoxidase assay. Results: Initially, only 5 of 12 patients had histologic columnar metaplasia (CM) and 7 did not, although each of these 12 patients were mAb Das-1 positive. Among these 5 patients with CM, we observed the disappearance of both antibody reactivity and CM in 2 patients. The remaining 3 patients with CM on initial histology continued to have antibody reactivity, although in 2 of the 3 CM disappeared at follow-up biopsy. In only 1 of the 5 patients, CM and mAb Das-1 reactivity persisted during the follow-up. The cohort of 7 of 12 patients exhibited mAb Das-1 reactivity in the absence of CM on initial endoscopy and histology. Five of 7 patients had disappearance of antibody reactivity and there was no CM in subsequent follow-up biopsy. Each of the 5 patients were treated with a PPI, and the treatment course was continuous in 3 and intermittent in 2 patients. Two of the 7 patients with no CM on entry into the study continued to be antibody positive at the time of follow-up. Conclusions: CM, as evidenced by mAb Das-1 reactivity, is present in some patients with symptomatic reflux in the absence of histological evidence of CM. PPI therapy may alter the disease course of this metaplasia if introduced at an early stage and probably with continued therapy.