INCREASED EXPRESSION OF INDUCIBLE NITRIC-OXIDE SYNTHASE AND CYCLOOXYGENASE-2 IN BARRETTS-ESOPHAGUS AND ASSOCIATED ADENOCARCINOMAS

Barrett's esophagus is a premalignant condition arising in response to chronic reflux esophagitis, Inducible nitric oxide synthase (iNOS; NO S-2) and cyclooxygenase-2 (COX-2) are mediators of inflammation and re gulators of epithelial cell growth. Expression levels of iNOS and COX- 2 are high in colorectal adenomas and carcinomas, and COX-2 expression is elevated in gastric cancers, To determine the involvement of iNOS and COX-2 in Barrett's-associated neoplasia, we measured expression of these genes in metaplastic Barrett's and esophageal adenocarcinomas. We detected elevated iNOS and COX-2 mRNA levels in Barrett's mucosa co mpared with paired gastric control tissues in 16 of 21 (76%) and 17 of 21 (80%) patients, respectively (P < 0.001 for both genes). In esopha geal adenocarcinomas, iNOS and COX-2 mRNA levels were increased in fou r of five and five of five cases, respectively. Furthermore, in 10 of 10 Barrett's patients, immunohistochemical staining for iNOS and COS-2 expression was strongly positive and higher than in matched gastric c ontrols. Increased COX-2 expression was confirmed by Western blotting. These findings support the hypothesis that iNOS and COX-2 are involve d early and often in Barrett's-associated neoplastic progression.