Prognostic significance of elevated cyclooxygenase 2 expression in patients with adenocarcinoma of the esophagus.
OBJECTIVE
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 immunohistochemically 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, log-rank 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 [CI], 23-47) and 72% (95% CI, 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% CI, 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.
Buskens
Christianne J
CJ
Department of Surgery, Academic Medical Center, University of Amsterdam, The Netherlands.
Van Rees
Bastiaan P
BP
Sivula
Anna
A
Reitsma
Johannes B
JB
Haglund
Caj
C
Bosma
Piter J
PJ
Offerhaus
G Johan A
GJ
Van Lanschot
J Jan B
JJ
Ristimäki
Ari
A
D000230:Adenocarcinoma / Q000201:enzymology* / Q000209:etiology / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001471:Barrett Esophagus / Q000150:complications; D015331:Cohort Studies; D051546:Cyclooxygenase 2; D004938:Esophageal Neoplasms / Q000201:enzymology* / Q000209:etiology / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D013194:Staining and Labeling; D016019:Survival Analysis
D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases