European Urology

Abstract

Objective

We investigated the potential involvement of the thromboxane A₂ (TXA₂) pathway in human prostate cancer (PCa).

Methods

Expression 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.

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.