TY - JOUR
T1 - Prognostic significance of elevated cyclooxygenase 2 expression in patients with adenocarcinoma of the esophagus
AU - Buskens, Christianne J.
AU - Van Rees, Bastiaan P.
AU - Sivula, Anna
AU - Reitsma, Johannes B.
AU - Haglund, Caj
AU - Bosma, Piter J.
AU - Offerhaus, G. JohanA
AU - Van Lanschot, J. Janb
AU - Ristimäki, Ari
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
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M3 - Article
C2 - 12055587
AN - SCOPUS:0036083347
SN - 0016-5085
VL - 122
SP - 1800
EP - 1807
JO - Gastroenterology
JF - Gastroenterology
IS - 7
ER -