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Cyclooxygenase-2 Expression Is a Novel Prognostic Factor in Malignant Mesothelioma
Ist Teil von
Clinical cancer research, 2002-06, Vol.8 (6), p.1857-1862
Ort / Verlag
Philadelphia, PA: American Association for Cancer Research
Erscheinungsjahr
2002
Quelle
Open access e-journals list
Beschreibungen/Notizen
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.