Cyclooxygenase 2 expression in Barrett's esophagus and adenocarcinoma: Ex vivo induction by bile salts and acid exposure

Background & Aims: Barrett's esophagus (BE) results from chronic, severe ga stroesophageal reflux and predisposes to:esophageal adenocarcinoma. Cycloox ygenase (COX)-2 is involved in chronic inflammation and epithelial cell gro wth. We investigated COX-2 expression in BE and esophageal adenocarcinoma t o explore a potential relation between COX-2 expression and metaplasia or c arcinogenesis. Methods: Endoscopic mucosal biopsy specimens of Barrett's in testinal metaplasia (n = 30), Barrett's dysplasia (n = 11), and esophageal adenocarcinoma (n = 5) were compared with normal esophagus (n = 46) and duo denum (n = 46) and analyzed by Western blotting and immunohistochemistry, R esults: Immunoblots revealed constitutive expression of COX-2 in normal eso phagus and duodenum. COX-2 protein expression was significantly higher in p atients with Barrett's metaplasia, dysplasia, and adenocarcinoma compared w ith normal squamous esophageal or columnar duodenal epithelia and was heter ogenous in different regions of the BE surface. Immunohistochemistry reveal ed prominent staining in the glands of BE, dysplasia, and adenocarcinoma an d faint staining in the basal layers of squamous esophagus and the surface of the duodenum. In response to pulses of acid or bile salts in an ex vivo organ culture system, COX-2 expression increased significantly in BE tissue s, and this effect was attenuated by the selective COX-2 inhibitor NS-398. Conclusions: The results show COX-2 expression in normal esophagus, which i ncreases significantly in BE and esophageal adenocarcinoma, COX-2 is regula ted ex vivo by exposure to acid or bile salts.