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Expression of urokinase-type plasminogen activator system in non-metastatic prostate cancer
S. Kimura, D. D'Andrea, T. Iwata, B. Foerster, F. Janisch, MK. Parizi, M. Moschini, A. Briganti, M. Babjuk, P. Chlosta, PI. Karakiewicz, D. Enikeev, LM. Rapoport, V. Seebacher, S. Egawa, M. Abufaraj, SF. Shariat
Jazyk angličtina Země Německo
Typ dokumentu časopisecké články
NLK
ProQuest Central
od 1997-02-01 do Před 1 rokem
Medline Complete (EBSCOhost)
od 2000-02-01 do Před 1 rokem
Health & Medicine (ProQuest)
od 1997-02-01 do Před 1 rokem
- MeSH
- aktivátor plasminogenu urokinasového typu biosyntéza fyziologie MeSH
- inhibitor aktivátoru plazminogenu 1 biosyntéza fyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru epidemiologie etiologie MeSH
- nádorové biomarkery biosyntéza fyziologie MeSH
- nádory prostaty epidemiologie etiologie metabolismus chirurgie MeSH
- prognóza MeSH
- prostatektomie * MeSH
- receptory urokinázového aktivátoru plazminogenu biosyntéza fyziologie MeSH
- retrospektivní studie MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
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.
Department of Gynecology and Gynecologic Oncology Medical University of Vienna Vienna Austria
Department of Urology Jagiellonian University Kraków Poland
Department of Urology Jikei University School of Medicine Tokyo Japan
Department of Urology Kantonsspital Winterthur Winterthur Switzerland
Department of Urology Shariati Hospital Tehran University of Medical Sciences Teheran Iran
Department of Urology University Medical Center Hamburg Eppendorf Hamburg Germany
Department of Urology University of Texas Southwestern Medical Center Dallas TX USA
Department of Urology Weill Cornell Medical College New York NY USA
Division of Urology University of Montreal Health Center Montreal QC Canada
Institute for Urology and Reproductive Health Sechenov University Moscow Russia
Karl Landsteiner Institute of Urology and Andrology Vienna Austria
Klinik für Urologie Luzerner Kantonsspital Lucerne Switzerland
Citace poskytuje Crossref.org
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- $a Kimura, Shoji $u Department of Urology and Comprehensive Cancer Center, Vienna General Hospital, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria $u Department of Urology, Jikei University School of Medicine, Tokyo, Japan
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- $a 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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