Prognostic significance of elevated cyclooxygenase 2 expression in patients with adenocarcinoma of the esophagus

Background & Aims: Use of nonsteroldal anti-inflammatory drugs (NSAIDs) is associated with a reduced risk of cancer In the digestive tract. Cyclooxygenase (COX) is the best-known target of NSAIDs, and expression of the COX-2 isoform is elevated In esophageal carcinomas but its clinical significance remains unclear. We examined COX-2 expression In esophageal adenocarcinomas and its relation to clinicopathologic parameters. Methods: Tumor sections from 145 consecutive patients undergoing Intentionally curative surgery for an adenocarcinoma arising from a Barrett's esophagus were Immunohistochemically stained using a COX-2-speclflc anti-human monoclonal antibody. The specimens were scored based on the intensity and extent of COX-2 Immunopositivity. Results: COX-2 immunoreactivity was negative to weak In 21% (COX-2 low) and moderate to strong In 79% (COX-2 high) of the carcinomas. Patients with high COX-2 expression were more likely to develop distant metastases (P = 0.02) and local recurrences (P = 0.05), and survival was significantly reduced (P = 0.002, logrank test) among patients with high COX-2 expression when compared with the COX-2 low group. Five-year survival rates were 35% (95% confidence Interval [Cl], 23-47) and 72% (95% Cl, 53-90) in COX-2 high and COX-2 low categories, respectively. Furthermore, expression of COX-2 was recognized as an Independent prognostic factor by multivariate analysis (relative risk, 3.5; 95% Cl, 1.6-7.9). Conclusions: Elevated expression of COX-2 protein Is associated with significantly reduced survival of patients undergoing surgery for esophageal adenocarcinoma. These findings support the effort to Initiate clinical studies to Investigate the effect of COX-2 inhibitors as a novel (adjuvant) chemotherapeutic modality for the treatment of adenocarcinoma arising from Barrett's esophagus.