Expression of urokinase-type plasminogen activator system in non-metastatic prostate cancer

Shoji Kimura, David D’Andrea, Takehiro Iwata, Beat Foerster, Florian Janisch, Mehdi Kardoust Parizi, Marco Moschini, Alberto Briganti, Marko Babjuk, Piotr Chlosta, Pierre I. Karakiewicz, Dmitry Enikeev, Leonid M. Rapoport, Veronica Seebacher, Shin Egawa, Mohammad Abufaraj, Shahrokh F. Shariat

Research output: Contribution to journalArticle

Abstract

Purpose: To investigate the prognostic role of expression of urokinase-type plasminogen activator system members, such as urokinase-type activator (uPA), uPA-receptor (uPAR), and plasminogen activator inhibitor-1 (PAI-1), in patients treated with radical prostatectomy (RP) for prostate cancer (PCa). Methods: Immunohistochemical staining for uPA system was performed on a tissue microarray of specimens from 3121 patients who underwent RP. Cox regression analyses were performed to investigate the association of overexpression of these markers alone or in combination with biochemical recurrence (BCR). Decision curve analysis was used to assess the clinical impact of these markers. Results: uPA, uPAR, and PAI-1 were overexpressed in 1012 (32.4%), 1271 (40.7%), and 1311 (42%) patients, respectively. uPA overexpression was associated with all clinicopathologic characteristics of biologically aggressive PCa. On multivariable analysis, uPA, uPAR, and PAI-1 overexpression were all three associated with BCR (HR: 1.75, p < 0.01, HR: 1.22, p = 0.01 and HR: 1.20, p = 0.03, respectively). Moreover, the probability of BCR increased incrementally with increasing cumulative number of overexpressed markers. Decision curve analysis showed that addition of uPA, uPAR, and PAI-1 resulted in a net benefit compared to a base model comparing standard clinicopathologic features across the entire threshold probability range. In subgroup analyses, overexpression of all three markers remained associated with BCR in patients with favorable pathologic characteristics. Conclusion: Overexpression of uPA, uPAR, and PAI-1 in PCa tissue were each associated with worse BCR. Additionally, overexpression of all three markers is informative even in patients with favorable pathologic characteristics potentially helping clinical decision-making regarding adjuvant therapy and/or intensified follow-up.

Original languageEnglish
JournalWorld Journal of Urology
DOIs
Publication statusAccepted/In press - Jan 1 2019

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Urokinase-Type Plasminogen Activator
Prostatic Neoplasms
Plasminogen Activator Inhibitor 1
Recurrence
Decision Support Techniques
Prostatectomy
Biomarkers
Regression Analysis
Staining and Labeling

Keywords

  • Biochemical recurrence
  • Prostate cancer
  • Radical prostatectomy
  • Urokinase-type plasminogen activator

ASJC Scopus subject areas

  • Urology

Cite this

Kimura, S., D’Andrea, D., Iwata, T., Foerster, B., Janisch, F., Parizi, M. K., ... Shariat, S. F. (Accepted/In press). Expression of urokinase-type plasminogen activator system in non-metastatic prostate cancer. World Journal of Urology. https://doi.org/10.1007/s00345-019-03038-5

Expression of urokinase-type plasminogen activator system in non-metastatic prostate cancer. / Kimura, Shoji; D’Andrea, David; Iwata, Takehiro; Foerster, Beat; Janisch, Florian; Parizi, Mehdi Kardoust; Moschini, Marco; Briganti, Alberto; Babjuk, Marko; Chlosta, Piotr; Karakiewicz, Pierre I.; Enikeev, Dmitry; Rapoport, Leonid M.; Seebacher, Veronica; Egawa, Shin; Abufaraj, Mohammad; Shariat, Shahrokh F.

In: World Journal of Urology, 01.01.2019.

Research output: Contribution to journalArticle

Kimura, S, D’Andrea, D, Iwata, T, Foerster, B, Janisch, F, Parizi, MK, Moschini, M, Briganti, A, Babjuk, M, Chlosta, P, Karakiewicz, PI, Enikeev, D, Rapoport, LM, Seebacher, V, Egawa, S, Abufaraj, M & Shariat, SF 2019, 'Expression of urokinase-type plasminogen activator system in non-metastatic prostate cancer', World Journal of Urology. https://doi.org/10.1007/s00345-019-03038-5
Kimura, Shoji ; D’Andrea, David ; Iwata, Takehiro ; Foerster, Beat ; Janisch, Florian ; Parizi, Mehdi Kardoust ; Moschini, Marco ; Briganti, Alberto ; Babjuk, Marko ; Chlosta, Piotr ; Karakiewicz, Pierre I. ; Enikeev, Dmitry ; Rapoport, Leonid M. ; Seebacher, Veronica ; Egawa, Shin ; Abufaraj, Mohammad ; Shariat, Shahrokh F. / Expression of urokinase-type plasminogen activator system in non-metastatic prostate cancer. In: World Journal of Urology. 2019.
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abstract = "Purpose: To investigate the prognostic role of expression of urokinase-type plasminogen activator system members, such as urokinase-type activator (uPA), uPA-receptor (uPAR), and plasminogen activator inhibitor-1 (PAI-1), in patients treated with radical prostatectomy (RP) for prostate cancer (PCa). Methods: Immunohistochemical staining for uPA system was performed on a tissue microarray of specimens from 3121 patients who underwent RP. Cox regression analyses were performed to investigate the association of overexpression of these markers alone or in combination with biochemical recurrence (BCR). Decision curve analysis was used to assess the clinical impact of these markers. Results: uPA, uPAR, and PAI-1 were overexpressed in 1012 (32.4{\%}), 1271 (40.7{\%}), and 1311 (42{\%}) patients, respectively. uPA overexpression was associated with all clinicopathologic characteristics of biologically aggressive PCa. On multivariable analysis, uPA, uPAR, and PAI-1 overexpression were all three associated with BCR (HR: 1.75, p < 0.01, HR: 1.22, p = 0.01 and HR: 1.20, p = 0.03, respectively). Moreover, the probability of BCR increased incrementally with increasing cumulative number of overexpressed markers. Decision curve analysis showed that addition of uPA, uPAR, and PAI-1 resulted in a net benefit compared to a base model comparing standard clinicopathologic features across the entire threshold probability range. In subgroup analyses, overexpression of all three markers remained associated with BCR in patients with favorable pathologic characteristics. Conclusion: Overexpression of uPA, uPAR, and PAI-1 in PCa tissue were each associated with worse BCR. Additionally, overexpression of all three markers is informative even in patients with favorable pathologic characteristics potentially helping clinical decision-making regarding adjuvant therapy and/or intensified follow-up.",
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AU - Kimura, Shoji

AU - D’Andrea, David

AU - Iwata, Takehiro

AU - Foerster, Beat

AU - Janisch, Florian

AU - Parizi, Mehdi Kardoust

AU - Moschini, Marco

AU - Briganti, Alberto

AU - Babjuk, Marko

AU - Chlosta, Piotr

AU - Karakiewicz, Pierre I.

AU - Enikeev, Dmitry

AU - Rapoport, Leonid M.

AU - Seebacher, Veronica

AU - Egawa, Shin

AU - Abufaraj, Mohammad

AU - Shariat, Shahrokh F.

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N2 - Purpose: To investigate the prognostic role of expression of urokinase-type plasminogen activator system members, such as urokinase-type activator (uPA), uPA-receptor (uPAR), and plasminogen activator inhibitor-1 (PAI-1), in patients treated with radical prostatectomy (RP) for prostate cancer (PCa). Methods: Immunohistochemical staining for uPA system was performed on a tissue microarray of specimens from 3121 patients who underwent RP. Cox regression analyses were performed to investigate the association of overexpression of these markers alone or in combination with biochemical recurrence (BCR). Decision curve analysis was used to assess the clinical impact of these markers. Results: uPA, uPAR, and PAI-1 were overexpressed in 1012 (32.4%), 1271 (40.7%), and 1311 (42%) patients, respectively. uPA overexpression was associated with all clinicopathologic characteristics of biologically aggressive PCa. On multivariable analysis, uPA, uPAR, and PAI-1 overexpression were all three associated with BCR (HR: 1.75, p < 0.01, HR: 1.22, p = 0.01 and HR: 1.20, p = 0.03, respectively). Moreover, the probability of BCR increased incrementally with increasing cumulative number of overexpressed markers. Decision curve analysis showed that addition of uPA, uPAR, and PAI-1 resulted in a net benefit compared to a base model comparing standard clinicopathologic features across the entire threshold probability range. In subgroup analyses, overexpression of all three markers remained associated with BCR in patients with favorable pathologic characteristics. Conclusion: Overexpression of uPA, uPAR, and PAI-1 in PCa tissue were each associated with worse BCR. Additionally, overexpression of all three markers is informative even in patients with favorable pathologic characteristics potentially helping clinical decision-making regarding adjuvant therapy and/or intensified follow-up.

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