Activation of the thromboxane A2 pathway in human prostate cancer correlates with tumor Gleason score and pathologic stage

Objective: We investigated the potential involvement of the thromboxane A(2) (TXA(2)) pathway in human prostate cancer (PCa). Methods: Expression of cyclooxygenase-2 (COX-2), TXA2 synthase (TXS), and TXA(2) receptors (TPRs), the main actors of the TXA2 pathway, was analyzed on serial tissue sections from 46 human PCa specimens. Results: The 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. Conclusions: Proteins 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. (c) 2006 European Association of Urology. Published by Elsevier B.V. All rights reserved.