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Molecular Changes at the Esophagogastric Junction (EGJ) in Patients with Symptomatic Gastroesophageal Reflux Disease (GERD) in the Absence of Histological Columnar Metaplasia (CM)


Bhandari, Bhavik M. MD; Pickett, Octavia E. MD; Amenta, Peter S. MD; Das, Kiron M. MD

American Journal of Gastroenterology: September 2006 - Volume 101 - Issue - p S61–S62
Abstracts: ESOPHAGUS

Medicine/GI, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ and Pathology, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ.

Purpose: We developed a novel monoclonal antibody, mAb Das-1, that recognizes Barrett's epithelium (BE) with 100% sensitivity and specificity. mAb Das-1 reacts with normal colon epithelium but does not react with normal esophagus, EGJ epithelium, gastric or small intestinal epithelium. COX-2 is expressed in the presence of inflammation and in BE. However, expression of these markers at the EGJ in patients with symptomatic GERD with normal histology is unknown.

Methods: Patients with symptomatic GERD (N = 86) were enrolled prospectively and 3 to 4 quadrantic biopsy specimens were taken from EGJ during endoscopy. Using immunoperoxidase assays, mAb Das-1 and anti-COX-2 antibody reactivity was assessed in serial sections of paraffin blocks of EGJ biopsy tissue. Thirty-six patients had normal histology, 50 had esophagitis and none had CM. Fourteen samples with adenocarcinoma of the esophagus were included. Normal biopsy specimens from the esophagus (N = 6), small bowel (N = 10) and colon (N = 15) were included as controls.

Results: mAb Das-1 reactivity at EGJ was observed in 4 of 36 (11%) patients with normal histology and 7 of 50 (14%) with esophagitis. COX-2 reactivity was found in 9 of 36 (25%) with normal histology and 20 of 50 (40%) with esophagitis. All 14 patients with adenocarcinoma reacted with both mAb Das-1 and anti-COX-2. Three of 4 (75%) patients with mAb Das-1 positivity with normal histology were also reactive to COX-2. COX-2 expression was absent in all control specimens. However, mAb Das-1 reactivity was present in colon epithelium but absent from esophagus and small bowel epithelium.

Conclusions: A metaplastic process expressing colonic phenotype of epithelium is found in 13% of EGJ biopsy tissue of symptomatic GERD patients in the absence of histologic CM. COX-2 expression was found in 34% of EGJ tissue of symptomatic GERD patients without CM. These data indicate that subclinical molecular changes at the EGJ, including metaplastic process, occur in some patients with GERD. This strongly supports the existence of a “pre-Barrett's” metaplastic stage. Such molecular diagnosis of early metaplastic process may allow initiation of early interventional treatment against further progression with PPI or other therapy.

© The American College of Gastroenterology 2006. All Rights Reserved.