Research and Reports in Urology (Apr 2019)

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

  • Nakahara K,
  • Yamasaki K,
  • Nagai T,
  • Fujii M,
  • Akioka T,
  • Takamori H,
  • Terada N,
  • Mukai S,
  • Sato Y,
  • Kamoto T

Journal volume & issue
Vol. Volume 11
pp. 97 – 104

Abstract

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Kozue Nakahara,1 Koji Yamasaki,1 Takahiro Nagai,1 Masato Fujii,1 Takahiro Akioka,1 Hiroki Takamori,1 Naoki Terada,1 Shoichiro Mukai,1 Yuichiro Sato,2 Toshiyuki Kamoto11Department of Urology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan; 2Section of Diagnostic Pathology, Faculty of Medicine, University of Miyazaki, Miyazaki, JapanBackground: 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.Keywords: PAR-2, matriptase, MET, NMIBC

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