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

Christianne J. Buskens, Bastiaan P. Van Rees, Anna Sivula, Johannes B. Reitsma, Caj Haglund, Piter J. Bosma, G. JohanA Offerhaus, J. Janb Van Lanschot, Ari Ristimäki

Research output: Contribution to journalArticle

Abstract

Background & Aims: Use of nonsteroidal 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 immunohisto chemically stained using a COX-2-specific 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.

Original languageEnglish (US)
Pages (from-to)1800-1807
Number of pages8
JournalGastroenterology
Volume122
Issue number7
StatePublished - 2002
Externally publishedYes

ASJC Scopus subject areas

  • Gastroenterology

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    Buskens, C. J., Van Rees, B. P., Sivula, A., Reitsma, J. B., Haglund, C., Bosma, P. J., Offerhaus, G. J., Van Lanschot, J. J., & Ristimäki, A. (2002). Prognostic significance of elevated cyclooxygenase 2 expression in patients with adenocarcinoma of the esophagus. Gastroenterology, 122(7), 1800-1807.