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Cyclooxygenase-2 Expression Is a Novel Prognostic Factor in Malignant Mesothelioma¹

Departments of Oncology [J. G. E., K. J. O.], Epidemiology and Public Health [K. R. A.], Pathology [R. A. W.], and Medical Research Council Toxicology Unit [S. P. F., S. M. P.], University of Leicester, Leicester, LE1 5WW, United Kingdom, and Department of Thoracic Surgery, Glenfield Hospital, Leicester, LE3 9QP, United Kingdom [J. G. E., D. A. W.]

Malignant mesothelioma (MM) is a fatal tumor of increasing incidence, which is resistant to current therapy. Cyclooxygenase-2 (COX-2) plays an important role in solid tumor growth, invasiveness, and angiogenesis, in part through the synthesis of prostaglandins such as prostaglandin E₂ (PGE₂). In a prospective study, we evaluated COX-2 expression in snap-frozen, surgically resected MM tissue specimens using immunohistochemistry and semiquantitative Western blotting. PGE₂ was assessed by enzyme immunoassay. Thirty epithelioid, 10 biphasic, and 8 sarcomatoid tumors were evaluated. Immunohistochemistry demonstrated strong cytoplasmic tumor cell and variable stromal staining in all of the cases. COX-2 protein levels were correlated with clinicopathological prognostic factors using Kaplan-Meier and Cox proportional hazards models. High COX-2 band densitometry values correlated with poor survival (P = 0.008). In multivariate analysis, high COX-2 expression (P = 0.0005), nonepithelioid cell type (P = 0.002), and chest pain (P = 0.04) were independent predictors of poor prognosis. Furthermore, COX-2 expression contributed in multivariate analysis to both European Organization for Research and Treatment of Cancer (P = 0.001) and Cancer and Leukemia Group B (P = 0.003) prognostic scoring systems. The presence of PGE₂ was demonstrated in all of the samples. These results suggest that COX-2 expression is a prognostic factor in MM. COX-2 is a potential therapeutic target in MM, and trials are required of COX-2 inhibitors alone or in combination with existing treatment modalities.

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