Comprehensive Evaluation of Prostate Specific Membrane Antigen Expression in the Vasculature of Renal Tumors: Implications for Imaging Studies and Prognostic Role

No AccessJournal of UrologyAdult Urology1 Feb 2018Comprehensive Evaluation of Prostate Specific Membrane Antigen Expression in the Vasculature of Renal Tumors: Implications for Imaging Studies and Prognostic Role Sophia Spatz, Yuri Tolkach, Klaus Jung, Carsten Stephan, Jonas Busch, Bernhard Ralla, Anja Rabien, Georg Feldmann, Peter Brossart, Ralph A. Bundschuh, Hojjat Ahmadzadehfar, Markus Essler, Marieta Toma, Stefan C. Müller, Jörg Ellinger, Stefan Hauser, and Glen Kristiansen Sophia SpatzSophia Spatz Clinic of Urology, University Hospital Bonn, Bonn, Germany Equal study contribution. More articles by this author , Yuri TolkachYuri Tolkach Institute of Pathology, University Hospital Bonn, Bonn, Germany Equal study contribution. More articles by this author , Klaus JungKlaus Jung Berlin Institute of Urologic Research and Department of Urology, Charité-Universitätsmedizin Berlin, Berlin, Germany More articles by this author , Carsten StephanCarsten Stephan Berlin Institute of Urologic Research and Department of Urology, Charité-Universitätsmedizin Berlin, Berlin, Germany More articles by this author , Jonas BuschJonas Busch Berlin Institute of Urologic Research and Department of Urology, Charité-Universitätsmedizin Berlin, Berlin, Germany More articles by this author , Bernhard RallaBernhard Ralla Berlin Institute of Urologic Research and Department of Urology, Charité-Universitätsmedizin Berlin, Berlin, Germany More articles by this author , Anja RabienAnja Rabien Berlin Institute of Urologic Research and Department of Urology, Charité-Universitätsmedizin Berlin, Berlin, Germany More articles by this author , Georg FeldmannGeorg Feldmann Clinic of Internal Medicine III, University Hospital Bonn, Bonn, Germany More articles by this author , Peter BrossartPeter Brossart Clinic of Internal Medicine III, University Hospital Bonn, Bonn, Germany More articles by this author , Ralph A. BundschuhRalph A. Bundschuh Clinic of Nuclear Medicine, University Hospital Bonn, Bonn, Germany More articles by this author , Hojjat AhmadzadehfarHojjat Ahmadzadehfar Clinic of Nuclear Medicine, University Hospital Bonn, Bonn, Germany More articles by this author , Markus EsslerMarkus Essler Clinic of Nuclear Medicine, University Hospital Bonn, Bonn, Germany More articles by this author , Marieta TomaMarieta Toma Institute of Pathology, University Hospital Bonn, Bonn, Germany More articles by this author , Stefan C. MüllerStefan C. Müller Clinic of Urology, University Hospital Bonn, Bonn, Germany More articles by this author , Jörg EllingerJörg Ellinger Clinic of Urology, University Hospital Bonn, Bonn, Germany More articles by this author , Stefan HauserStefan Hauser Clinic of Urology, University Hospital Bonn, Bonn, Germany Senior authors. More articles by this author , and Glen KristiansenGlen Kristiansen Institute of Pathology, University Hospital Bonn, Bonn, Germany Senior authors. More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.08.079AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Prostate specific membrane antigen is expressed by the endothelium of many tumors. The aim of the study was to find a rationale for prostate specific membrane antigen based imaging and investigate the prognostic role of vascular prostate specific membrane antigen expression in patients with renal cell carcinoma. Materials and Methods: A total of 257 patients with renal cell carcinoma were included in study with a median followup exceeding 10.0 years. Prostate specific membrane antigen expression on tumor vessels was detected by immunohistochemistry. Vascular expression of FOLH1 gene (prostate specific membrane antigen) mRNA was investigated in clear cell carcinoma and papillary renal cell carcinoma using TCGA (The Cancer Genome Atlas) data. Results: Endothelial prostate specific membrane antigen protein expression was higher in clear cell than in papillary and chromophobe renal cell carcinoma. Higher grade and stage, metastatic and lethal clear cell renal cell carcinoma showed higher prostate specific membrane antigen expression in tumor vessels. On univariate and multivariate analysis the intensity of positive vs negative endothelial prostate specific membrane antigen protein expression was significantly associated with overall survival. TCGA based analyses confirmed the prognostic role of vascular expression of FOLH1 mRNA. The analyses also supported the usefulness of prostate specific membrane antigen based imaging in cases of clear cell but not papillary renal cell carcinoma. Conclusions: We provide a rationale for further development of prostate specific membrane antigen targeted imaging in patients with clear cell renal cell carcinoma. The prognostic role of prostate specific membrane antigen was determined at the protein level in clear cell renal cell carcinoma and at the mRNA level in clear cell and papillary renal cell carcinoma. References 1 : Prostate-specific membrane antigen is produced in tumor-associated neovasculature. Clin Cancer Res1999; 5: 2674. Google Scholar 2 : PSMA uptake in mediastinal sarcoidosis. Clin Nucl Med2017; 42: 303. Google Scholar 3 : Quantitative parameters in PSMA-targeted PET imaging with 18F-DCFPyL: variability in normal organ uptake. J Nucl Med2017; 58: 942. Google Scholar 4 : Claudin-1 protein expression is a prognostic marker of patient survival in renal cell carcinomas. Clin Cancer Res2008; 14: 7035. 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Google Scholar © 2018 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 199Issue 2February 2018Page: 370-377Supplementary Materials Advertisement Copyright & Permissions© 2018 by American Urological Association Education and Research, Inc.Keywordsrenal cellcarcinomamortalityglutamate carboxypeptidase IIhumancarcinomadiagnostic imagingpapillaryMetricsAuthor Information Sophia Spatz Clinic of Urology, University Hospital Bonn, Bonn, Germany Equal study contribution. More articles by this author Yuri Tolkach Institute of Pathology, University Hospital Bonn, Bonn, Germany Equal study contribution. More articles by this author Klaus Jung Berlin Institute of Urologic Research and Department of Urology, Charité-Universitätsmedizin Berlin, Berlin, Germany More articles by this author Carsten Stephan Berlin Institute of Urologic Research and Department of Urology, Charité-Universitätsmedizin Berlin, Berlin, Germany More articles by this author Jonas Busch Berlin Institute of Urologic Research and Department of Urology, Charité-Universitätsmedizin Berlin, Berlin, Germany More articles by this author Bernhard Ralla Berlin Institute of Urologic Research and Department of Urology, Charité-Universitätsmedizin Berlin, Berlin, Germany More articles by this author Anja Rabien Berlin Institute of Urologic Research and Department of Urology, Charité-Universitätsmedizin Berlin, Berlin, Germany More articles by this author Georg Feldmann Clinic of Internal Medicine III, University Hospital Bonn, Bonn, Germany More articles by this author Peter Brossart Clinic of Internal Medicine III, University Hospital Bonn, Bonn, Germany More articles by this author Ralph A. Bundschuh Clinic of Nuclear Medicine, University Hospital Bonn, Bonn, Germany More articles by this author Hojjat Ahmadzadehfar Clinic of Nuclear Medicine, University Hospital Bonn, Bonn, Germany More articles by this author Markus Essler Clinic of Nuclear Medicine, University Hospital Bonn, Bonn, Germany More articles by this author Marieta Toma Institute of Pathology, University Hospital Bonn, Bonn, Germany More articles by this author Stefan C. Müller Clinic of Urology, University Hospital Bonn, Bonn, Germany More articles by this author Jörg Ellinger Clinic of Urology, University Hospital Bonn, Bonn, Germany More articles by this author Stefan Hauser Clinic of Urology, University Hospital Bonn, Bonn, Germany Senior authors. More articles by this author Glen Kristiansen Institute of Pathology, University Hospital Bonn, Bonn, Germany Senior authors. More articles by this author Expand All Advertisement PDF downloadLoading ...