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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Oncol. | doi: 10.3389/fonc.2018.00623

Expression of Prostate-Specific Membrane Antigen (PSMA) on Biopsies is an Independent Risk Stratifier of Prostate Cancer Patients at Time of Initial Diagnosis

 Marie C. Hupe1,  Christian Philippi2, Doris Roth2,  Christiane Kümpers2,  Julika Ribbat-Idel2, Finn Becker2, Vincent Joerg2,  Stefan Duensing2,  Verena H. Lubczyk3, Jutta Kirfel2, Verena Sailer2, Rainer Kuefer4,  Axel S. Merseburger1,  Sven Perner2* and  Anne Offermann2
  • 1Klinik für Urologie, Universitätsklinikum Schleswig-Holstein, Germany
  • 2Institut für Pathologie, Universität zu Lübeck, Germany
  • 3Institut für Pathologie, Klinik am Eichert Alb Fils Kliniken, Germany
  • 4Klinik für Urologie, Klinik am Eichert Alb Fils Kliniken, Germany

Background:
Stratifying PCa patients into risk groups at time of initial diagnosis enabling a risk-adapted disease management is still a major clinical challenge. Existing studies evaluating the prognostic potential of PSMA for PCa were performed on radical prostatectomy specimens (RPE), i.e. decision making for disease management was already completed at time of sample analysis. Aim of our study was to assess the prognostic value of PSMA (prostate-specific membrane antigen) expression for prostate cancer (PCa) patients on biopsies at time of initial diagnosis.

Methods:
PSMA expression was assessed by immunohistochemistry on 294 prostate biopsies with corresponding RPE, 621 primary tumor foci from 242 RPE, 43 locally advanced or recurrent tumors, 34 lymph node metastases, 78 distant metastases and 52 benign prostatic samples. PSMA expression was correlated with clinico-pathologic features. Primary endpoint was recurrence free survival. Other clinicopathologic features included WHO/ISUP grade groups, PSA serum level, TNM-stage, and R-status. Chi-square test, ANOVA-analyses, Cox-regression and log-rank tests were performed for statistical analyses.

Results:
High PSMA expression on both biopsy and RPE significantly associates with a higher risk of disease recurrence following curative surgery. The 5-year-recurrence free survival rates were 88.2%, 74.2%, 67.7% and 26.8% for patients exhibiting no, low, medium or high PSMA expression on biopsy, respectively. High PSMA expression on biopsy was significant in multivariate analysis predicting a 4-fold increased risk of disease recurrence independently from established prognostic markers. PSMA significantly increases during PCa progression.

Conclusion:
PSMA is an independent prognostic marker on biopsies at time of initial diagnosis and can predict disease recurrence following curative therapy for PCa. Our study proposes the application of the routinely used IHC marker PSMA for outcome prediction and decision making in risk-adapted PCa management on biopsies at time of initial diagnosis.

Keywords: Disease recurrence, Immunohistochemistry, prognostic marker, prostate biopsy, prostate cancer, prostate-specific membrane antigen (PSMA)

Received: 08 Oct 2018; Accepted: 30 Nov 2018.

Edited by:

George Kulik, Wake Forest University, United States

Reviewed by:

Atreya Dash, University of Washington, United States
Francesca Sanguedolce, Azienda Ospedaliero-Universitaria Ospedali Riuniti di Foggia, Italy  

Copyright: © 2018 Hupe, Philippi, Roth, Kümpers, Ribbat-Idel, Becker, Joerg, Duensing, Lubczyk, Kirfel, Sailer, Kuefer, Merseburger, Perner and Offermann. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Sven Perner, Institut für Pathologie, Universität zu Lübeck, Luebeck, Germany, sven.perner@uksh.de