Cyclooxygenase-2 expression is a novel prognostic factor in malignant mesothelioma.
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 E(2) (PGE(2)). In a prospective study, we evaluated COX-2 expression in snap-frozen, surgically resected MM tissue specimens using immunohistochemistry and semiquantitative Western blotting. PGE(2) 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 PGE(2) 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.
Edwards
John G
JG
University Department of Oncology, Osborne Building, Royal Infirmary, University of Leicester, Leicester, LE1 5WW, United Kingdom.
Faux
Stephen P
SP
Plummer
Simon M
SM
Abrams
Keith R
KR
Walker
Rosemary A
RA
Waller
David A
DA
O'Byrne
Kenneth J
KJ
D014408:Biomarkers, Tumor / Q000378:metabolism; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D008654:Mesothelioma / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology; D010997:Pleural Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D015996:Survival Rate
D014408:Biomarkers, Tumor; D007527:Isoenzymes; D008565:Membrane Proteins; D010446:Peptide Fragments; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone