Cyclooxygenase-2 Protein Expression in Relation to Apoptotic Potential and its Prognostic Significance in Bladder Urothelial Carcinoma

Abstract

Background: Cyclooxygenase-2 (COX-2), a critical enzyme in the conversion of arachidonic acid to prostaglandin E2, influences the biological behavior of human tumors, being involved in carcinogenesis, tumor progression, reduced apoptosis and differentiation. The aim of the present study was to investigate the role of COX-2 protein expression in urothelial carcinoma (UC) of the urinary bladder in relation to clinicopathological data and indices of apoptotic potential. Materials and Methods: Immunohistochemistry was applied to 134 paraffin-embedded specimens of UC for the detection of COX-2, p53, bcl-2, caspase-3, bax protein, MLH1 and hTERT. Results: Ninety-four UCs (70.1%) had an enhanced expression of COX-2. The COX-2 semi-quantitative expression was unrelated to tumor grade and local invasion, but it was positively linked with caspase-3 (CPP32) and bax protein semi-quantitative immunoreactivity (p=0.007 and p=0.026), as well as with the quantitative expression of MLH1 (p=0.019). COX-2 was also found to be inversely correlated with the nuclear localization of the catalyst component of the telomerase complex, hTERT (p=0.009). Multivariate statistical analysis showed that COX-2 immunopositivity was independently associated with worse prognosis of patients with non muscle-invasive UCs (p=0.002). Conclusion: COX-2 overexpression, being possibly a subsequence of apoptosis activation, is associated with an unfavorable overall survival of patients with pTa-T1 UCs.