Overexpression of nuclear AR-V7 protein in primary prostate cancer is an independent negative prognostic marker in men with high-risk disease receiving adjuvant therapy

• Verfasst von: Chen, Xin [VerfasserIn]
• Verfasst von: Heller, Martina [VerfasserIn]
• Verfasst von: Nientiedt, Cathleen [VerfasserIn]
• Verfasst von: Falkenstein, Michael [VerfasserIn]
• Verfasst von: Herpel, Esther [VerfasserIn]
• Verfasst von: Jenzer, Maximilian [VerfasserIn]
• Verfasst von: Grüllich, Carsten [VerfasserIn]
• Verfasst von: Jäger, Dirk [VerfasserIn]
• Verfasst von: Hohenfellner, Markus [VerfasserIn]
• Verfasst von: Duensing, Stefan [VerfasserIn]
• Verfasst von: Sültmann, Holger [VerfasserIn]
• Verfasst von: Debus, Jürgen [VerfasserIn]
• Titel: Overexpression of nuclear AR-V7 protein in primary prostate cancer is an independent negative prognostic marker in men with high-risk disease receiving adjuvant therapy
• Verf.angabe: Xin Chen, Christof Bernemann, Yuri Tolkach, Martina Heller, Cathleen Nientiedt, Michael Falkenstein, Esther Herpel, Maximilian Jenzer, Carsten Grüllich, Dirk Jäger, Holger Sültmann, Anette Duensing, Sven Perner, Marcus V. Cronauer, Carsten Stephan, Jürgen Debus, Andres Jan Schrader, Glen Kristiansen, Markus Hohenfellner, Stefan Duensing
• Jahr: 2018
• Umfang: 12 S.
• Fussnoten: Gesehen am 02.07.2018 ; Available online 1 December 2017
• Titel Quelle: Enthalten in: Urologic oncology
• Ort Quelle: Amsterdam [u.a.] : Elsevier Science, 1995
• Jahr Quelle: 2018
• Band/Heft Quelle: 36(2018), 4, Seite 161.e19-161.e30
• ISSN Quelle: 1873-2496
• DOI: doi:10.1016/j.urolonc.2017.11.001
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Adjuvant therapy
• Sach-SW: Androgen receptor
• Sach-SW: AR-V7
• Sach-SW: Prostate cancer
• K10plus-PPN: 157714130X

Abstract

Background Overexpression of the androgen receptor (AR) splice variant 7 (AR-V7) has recently been reported to be associated with resistance to antihormonal therapy. Herein, we address the question whether tumor cells with AR-V7 expression can be detected at the time of radical prostatectomy, that is, before long-term hormonal manipulation and castration resistance, and what the potential prognostic impact on the biochemical recurrence (BCR)-free survival may be.Methods An anti-AR-V7 antibody was first validated in a training set of prostate cancer specimens by a comparison of AR-V7 protein to AR-V7 mRNA expression. We then analyzed nuclear AR-V7 protein expression in the primary tumors and lymph node metastases from 163 predominantly high-risk patients (cohort I) as well as the primary tumors from patients of a second, consecutive patient cohort (n = 238, cohort II) not selected for any clinicopathological features. Staining results were correlated to patient characteristics and BCR-free patient survival.Results High nuclear AR-V7 protein expression was detected in approximately 30%-40% of patients in cohort I and II at the time of radical prostatectomy. High baseline expression of nuclear AR-V7 protein was associated with an unfavorable BCR-free survival in the high-risk patient cohort I but not in the unselected consecutive cohort II. Remarkably, AR-V7 was an independent negative prognostic factor in high-risk prostate cancer patients of cohort I who were selected to receive adjuvant treatment.Conclusions Prostate cancer cells with high nuclear AR-V7 protein expression can be detected in a substantial proportion of tumors at the time of radical prostatectomy. The presence of AR-V7-positive tumor cells is associated with an unfavorable prognosis for BCR-free survival in a high-risk patient cohort including a subgroup of patients selected to receive adjuvant therapy, in which AR-V7 was an independent negative prognosticator. Overexpression of nuclear AR-V7 protein hence identifies a subset of tumors with remarkably aggressive growth characteristics among clinically and histologically high-risk patients at the time of radical prostatectomy.