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Cyclooxygenase-2 Expression in Human Colorectal Cancer Is Unrelated to Overall Patient Survival

Authors' Affiliations: ¹ Abteilung Klinische Pharmakologie, Institut für Pharmakologie und Toxikologie, Universitätsklinikum Tübingen, Tübingen, Germany; ² Dr. Margarete Fischer-Bosch-Institut für Klinische Pharmakologie Stuttgart; and ³ Abteilung Allgemein-, Visceral- und Unfallchirurgie am Zentrum für operative Medizin and ⁴ Abteilung für Pathologie am Zentrum für diagnostische Medizin, Robert Bosch-Krankenhaus Stuttgart, Stuttgart, Germany

Requests for reprints: Christoph H. Gleiter, Abteilung Klinische Pharmakologie, Institut für Pharmakologie und Toxikologie, Universitätsklinikum Tübingen, Otfried-Müller-Str. 45, D-72076 Tübingen, Germany. Phone: 49-7071-29-78277; Fax: 49-7071-29-5035; E-mail: christoph.gleiter{at}med.uni-tuebingen.de.

Purpose: Cyclooxygenase-2 (COX-2) expression in human colorectal cancer and adenoma tissue seems to be higher than in normal mucosa. However, data about the relation between COX-2 expression and patient survival are inconclusive as yet. Therefore, we studied COX-2 expression in surgery tissue and survival time in a cohort of 747 colorectal cancer patients.

Experimental Design: Surgical specimens of primary colorectal cancer from 747 individuals were immunostained for COX-2 and evaluated under a transmission light microscope. COX-2 expression was scored according to intensity and extent of staining, resulting in the COX-2 immunoreactivity score (IRS-COX2). All possible cutoff points for IRS-COX2 were analyzed for a relation between COX-2 expression and patient survival.

Results: Both univariable and multivariable analysis have shown that the COX-2 expression in human tumor epithelial cells was unrelated to overall patient survival and to disease-free survival, irrespectively of the cutoff point for IRS-COX2. The survival rates for 1, 3, 5, and 10 years were 81.0%, 66.8%, 60.2%, and 49.8% (median: 117.3 months; 95% confidence interval, 102.3-132.0), respectively. In the multivariable analysis, only node and metastasis were significantly related to overall patient survival. Similar results were obtained when stage IV and rectal cancer patients were excluded from the analysis.

Conclusions: COX-2 expression in tumor epithelial cells does not seem to be related to survival of colorectal cancer patients. Besides COX-2, there are several targets, such as the peroxisome proliferator–activated receptors, that are involved in carcinogenesis and may be modulated by nonsteroidal anti-inflammatory drugs. Further studies are needed to determine their prognostic relevance.

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