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Expression of Urokinase-Type Plasminogen Activator System in Non-Metastatic Prostate Cancer Publisher Pubmed



Kimura S1, 2 ; Dandrea D1 ; Iwata T1, 3 ; Foerster B1, 4 ; Janisch F1, 5 ; Parizi MK1, 6 ; Moschini M1, 7, 8 ; Briganti A8 ; Babjuk M9 ; Chlosta P10 ; Karakiewicz PI11 ; Enikeev D12 ; Rapoport LM12 ; Seebacher V13 Show All Authors
Authors
  1. Kimura S1, 2
  2. Dandrea D1
  3. Iwata T1, 3
  4. Foerster B1, 4
  5. Janisch F1, 5
  6. Parizi MK1, 6
  7. Moschini M1, 7, 8
  8. Briganti A8
  9. Babjuk M9
  10. Chlosta P10
  11. Karakiewicz PI11
  12. Enikeev D12
  13. Rapoport LM12
  14. Seebacher V13
  15. Egawa S2
  16. Abufaraj M1, 14
  17. Shariat SF1, 12, 15, 16, 17

Source: World Journal of Urology Published:2020


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. © 2019, Springer-Verlag GmbH Germany, part of Springer Nature.
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