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

木村, 章嗣 東京慈恵会医科大学 DOI:info:doi/10.1007/s00345-019-03038-5

2020.10.21

概要

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 3,121 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 1,012 (32.4%), 1,271 (40.7%) and 1,311 (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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