The potential of PAI-1 expression in needle biopsies as a predictive marker for prostate cancer

Antonio Serafin,Lothar Böhm,John Akudugu,Pedro Fernandez,Daniel Achel,Udo Schumacher

doi:10.1080/2331205x.2016.1183275

Abstract

AbstractThe relative abundance of urokinase plasminogen activator (uPA) and plasminogen activator inhibitor type-1 (PAI-1) in transurethral resections of the prostate (TURP) has been shown to correlate with disease state. The objective of this study was to assay for uPA and PAI-1 in prostate needle biopsies, and to test their potential as predictive markers for prostate cancer (PCa). uPA and PAI-1 levels were determined for 111 patients (55 PCa; 56 benign prostatic hyperplasia (BPH)), using the FEMTELLE enzyme-linked immunosorbent (ELISA) assay. The PAI-1 concentrations for PCa and BPH patients differed significantly (p = 0.0403) and a level of ≥ 4.5 ng/mg protein in men 60 years and older appears to be predictive of PCa, with a sensitivity of 63%. uPA plays a minor role as a potential marker in biopsy tissue, a feature noted in our recent TURP tissue studies, and elsewhere. The potential utility of the uPA/PAI-1 ratio as a predictor of prostate disease, as previously suggested for TURP tissue, is not app...

Highlights

Urokinase plasminogen activator and plasminogen activator inhibitor type-1 (PAI-1) play an important role in tumor invasion and metastasis (Duffy, McGowan, Harbeck, Thomssen, & Schmitt, 2014; Schmitt et al, 2011; Shariat et al, 2007)
Our findings suggest that PAI-1, and not Urokinase plasminogen activator (uPA), levels in prostate biopsies from elderly patients might potentially be useful as a predictive marker for prostate disease
We demonstrated that uPA/PAI-1 ratios derived from transurethral resection of the prostate (TURP) tissues from patients with prostate cancer (PCa) were significantly higher than those in their benign prostatic hyperplasia (BPH) counterparts (Akudugu, Serafin, & Böhm, 2015; Böhm et al, 2013)

Summary

Introduction

Urokinase plasminogen activator (uPA) and plasminogen activator inhibitor type-1 (PAI-1) play an important role in tumor invasion and metastasis (Duffy, McGowan, Harbeck, Thomssen, & Schmitt, 2014; Schmitt et al, 2011; Shariat et al, 2007). Optimized cut-off concentrations of >3 ng/mg protein and >14 ng/mg protein for uPA and PAI-1, respectively, are associated with tumor aggressiveness and a poor prognosis in node-negative breast cancer (Annecke et al, 2008; Harbeck et al, 1999). The clinical value of uPA and PAI-1 determination is, at present, still limited to breast cancer. No Level 1 evidence of clinical usefulness has been demonstrated for these two markers in other malignancies. In addition to being found in patients with prostate cancer (PCa), a raised PSA level may be found in individuals with BPH, inflammation of the prostate, or an infection. There is little correlation between PSA levels and tumor aggressiveness. The value of PSA screening in decreasing the mortality rate has been questioned by PCa screening studies (Andriole et al, 2009; Schröder et al, 2009)

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