Activation of the Thromboxane A2 Pathway in Human Prostate Cancer Correlates with Tumor Gleason Score and Pathologic Stage

ObjectiveWe investigated the potential involvement of the thromboxane A2 (TXA2) pathway in human prostate cancer (PCa).MethodsExpression of cyclooxygenase-2 (COX-2), TXA2 synthase (TXS), and TXA2 receptors (TPRs), the main actors of the TXA2 pathway, was analyzed on serial tissue sections from 46 human PCa specimens.ResultsThe expression levels of COX-2, TXS, and TPRs were significantly higher in malignant than in corresponding nontumoral prostatic epithelial cells. Increased immunoreactivity for these antigens was also observed in high-grade prostate intraepithelial neoplasia (HGPIN) glands. COX-2, TXS, and TPR proteins usually displayed a coordinated overexpression pattern in PCa lesions, as assessed in serial tissue sections. Increased levels of these proteins in the tumors were all significantly associated with higher Gleason scores and pathologic stages.ConclusionsProteins specifically involved in the TXA2 pathway are up-regulated in human PCa and their level of expression is associated with tumor extraprostatic extension and loss of differentiation. Our study is the first to examine simultaneously all key proteins involved in this pathway including TXA2 receptors and results suggest that the TXA2 pathway may be a potential target for PCa prevention/therapy.