Increased Expression of Inducible Nitric Oxide Synthase and Cyclooxygenase-2 in Barrett's Esophagus and Associated Adenocarcinomas1

Barrett's esophagus is a premalignant condition arising in response to chronic reflux esophagitis. Inducible nitric oxide synthase (¡NOS;NOS-2) and cyclooxygenase-2 (COX-2) are mediators of inflammation and regu lators of epithelial cell growth. Expression levels of ¡NOSand COX-2 are high in colorectal adenomas and carcinomas, and COX-2 expression is elevated in gastric cancers. To determine the involvement of ¡NOSand COX-2 in Barrett's-associated neoplasia, we measured expression of these genes in metaplastic Barrett's and esophageal adenocarcinomas. We de tected elevated ¡NOSand COX-2 niKNA levels in Barrett's mucosa com pared with paired gastric control tissues in 16 of 21 (76%) and 17 of 21 (80%) patients, respectively (/' < 0.001 for both genes). In esophageal adenocarcinomas, ¡NOSand COX-2 inKNA levels were increased in four of five and five of five cases, respectively. Furthermore, in 10 of 10 Barrett's patients, immunohistochemical staining for ¡NOSand COX-2 expression was strongly positive and higher than in matched gastric controls. Increased COX-2 expression was confirmed by Western blotting. These findings support the hypothesis that ¡NOSand COX-2 are involved early and often in Barrett's-associated neoplastic progression.