Background: Little is known about the role of COX-2 in gastroesophageal reflux disease (GERD) and development of Barrett's metaplasia. The objectives of this study were to further analyze COX-2 expression in patients with GERD compared to Barrett's esophagus and Barrett's cancer.
Methods: Tissue samples were obtained at endoscopy from 3 patient groups: group 1: squamous epithelium of the distal esophagus from patients with typical clinical symptoms indicative of GERD (n=43); group 2: specialized intestinal metaplasia (n=20), and group 3: esophageal adenocarcinoma in Barrett's esophagus (n=47). For normal tissue controls for each study group paired biopsies from the proximal esophagus were obtained. Expression levels of COX-2 were measured by quantitative real-time reverse trancriptase - polymerase chain reaction (RT-PCR). Also, 24h pH-monitoring was performed in all patients of the GERD study group and the DeMeester composite score was used to match COX-2 mRNA expression levels with the severity of acid exposure in the lower esophagus.
Results: We could confirm a significant (p <0.001) progressive COX-2 mRNA upregulation within the metaplasia-dysplasia-adenocarcinoma (MDA) sequence. COX-2 mRNA levels of the squamous epithelium in the distal esophagus from patients with GERD and a pathologic mean DeMeester score > 14.72 were significantly (p < 0.01) higher than in the group with normal DeMeester scores. Squamous epithelium from the proximal esophagus showed significantly lower COX-2 mRNA levels that did not differ between both groups (p = 0.18; DeMeester score ≤ 14.72 versus > 14.72).
Conclusion: Our findings demonstrate significant upregulation of COX-2 mRNA expression in the acid exposed squamous epithelium of the distal esophagus compared to non-exposed epithelium in the cervical esophagus in patients with GERD and a pathologic DeMeester score. This early COX-2 increase in GERD patients however, is further upregulated in Barrett's MDA sequence for yet unknown reasons.