<p>Expression of protease activating receptor-2 (PAR-2) is positively correlated with the recurrence of non-muscle invasive bladder cancer: an immunohistochemical analysis</p>

Abstract

Background: Matriptase, which is a Type II transmembrane serine protease, has the potential to activate several growth factors, including pro-hepatocyte growth factor (HGF). A G protein-coupled transmembrane cell-surface receptor and a protease-activated receptor 2 (PAR-2) are also required for activation by matriptase. Activation of PAR-2 has been reported to induce the progression of various cancers. In a previous study, we evaluated the correlation between upregulation of MET phosphorylation with high matriptase expression and worse prognosis in patients with muscle invasive bladder cancer; however, expression of PAR-2, matriptase and MET in non-muscle invasive bladder cancer (NMIBC) has not been evaluated. Materials and methods: We retrospectively analyzed the expression of PAR-2, matriptase and MET using 55 paraffin-embedded specimens obtained from patients with NMIBC by immunohistochemistry. Results: MET was significantly expressed in high-grade urothelial carcinoma (UC) and pathological T1 cancers. High expression of PAR-2 was significantly associated with a worse recurrence rate in NMIBC. In subgroup analysis, the expression of PAR-2 was also correlated with high recurrence rate in low-grade UC. In addition, expression of matriptase tended to correlate with worse recurrence rate in high-grade UC. Conclusion: Increased expression of PAR-2 was significantly correlated with worse recurrence rate in patients with NMIBC. In addition, expression of matriptase also indicated a tendency toward recurrence in high-grade UC, suggesting an important role of matriptase-induced PAR-2 activation in NMIBC.

Dysregulation of Type II Transmembrane Serine Proteases and Ligand-Dependent Activation of MET in Urological Cancers

“…Pathological analysis shows that approximately 90% of bladder cancers are UC and that 5% are squamous cell carcinoma [95]. Several studies reported a positive correlation between increased expression of MET and high tumor grade, pathological staging, and survival [96][97][98][99][100]. Phosphorylation was also analyzed by immunohistochemistry [97,98].…”