Adam Kaczorowski1, Xin Chen1, Esther Herpel2, Axel S Merseburger3, Glen Kristiansen4, Christof Bernemann5, Markus Hohenfellner6, Marcus V Cronauer7, Stefan Duensing8. 1. Molecular Urooncology, Department of Urology, University Hospital Heidelberg, Im Neuenheimer Feld 517, Heidelberg, D-69120, Germany. 2. Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, Heidelberg, D-69120, Germany; Tissue Bank of the National Center for Tumor Diseases (NCT) Heidelberg, Im Neuenheimer Feld 224, Heidelberg, D-69120, Germany. 3. Department of Urology, University Medical Center Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, Lübeck, D-23538, Germany. 4. Institute of Pathology, University Hospital Bonn, Sigmund-Freud-Strasse 25, Bonn, D-53127, Germany. 5. Department of Urology, University Hospital Münster, Albert-Schweitzer Campus 1, Münster, D-48149, Germany. 6. Department of Urology, University Hospital Heidelberg, National Center for Tumor Diseases (NCT) Heidelberg, Im Neuenheimer Feld 110, Heidelberg, D-69120, Germany. 7. Department of Urology, University Medical Center Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, Lübeck, D-23538, Germany; Institute of Pathology, University Hospital Bonn, Sigmund-Freud-Strasse 25, Bonn, D-53127, Germany. Electronic address: marcus.cronauer@ukbonn.de. 8. Molecular Urooncology, Department of Urology, University Hospital Heidelberg, Im Neuenheimer Feld 517, Heidelberg, D-69120, Germany; Department of Urology, University Hospital Heidelberg, National Center for Tumor Diseases (NCT) Heidelberg, Im Neuenheimer Feld 110, Heidelberg, D-69120, Germany. Electronic address: stefan.duensing@med.uni-heidelberg.de.
Abstract
BACKGROUND: The androgen receptor (AR) splice variant V7 (AR-V7) is an emerging marker to aid clinical decision-making in patients with castration-resistant prostate cancer (CRPC). A number of studies have shown that a subset of patients also express AR-V7 in the primary tumor. These findings have recently been challenged by a study showing that AR-V7 becomes only detectable in CRPC but is virtually absent in castration-naïve prostate cancer. METHODS: Herein, we directly compare the two relevant antibodies used for the immunodetection of AR-V7 in the conflicting studies (clones AG10008 and RM7) in a predominantly high-risk prostate cancer patient cohort with primary tumor specimens assembled in a tissue microarray (TMA). RESULTS: The overall rate of AR-V7 positive TMA cores was comparable (AG10008, 24.9%; RM7, 21%). However, the percentage agreement of identical staining intensities of positive cores was only 7%. In contrast, the percentage agreement of negative cores was 62.8%. In approximately 30% of the cores, the antibodies produced discordant staining intensities. Only one of the two antibody stainings (AG10008) conveyed prognostic information and was associated with a shorter progression-free patient survival. CONCLUSIONS: Our study underscores that nuclear AR-V7 expression can be detected in primary prostate cancer prior to long-term androgen deprivation and castration resistance. There are staining differences between the two antibodies in tumor tissue, for which we currently have no explanation. Clearly, improvements in the detection of functional AR-V7 in prostate cancer are urgently needed.
BACKGROUND: The androgen receptor (AR) splice variant V7 (AR-V7) is an emerging marker to aid clinical decision-making in patients with castration-resistant prostate cancer (CRPC). A number of studies have shown that a subset of patients also express AR-V7 in the primary tumor. These findings have recently been challenged by a study showing that AR-V7 becomes only detectable in CRPC but is virtually absent in castration-naïve prostate cancer. METHODS: Herein, we directly compare the two relevant antibodies used for the immunodetection of AR-V7 in the conflicting studies (clones AG10008 and RM7) in a predominantly high-risk prostate cancer patient cohort with primary tumor specimens assembled in a tissue microarray (TMA). RESULTS: The overall rate of AR-V7 positive TMA cores was comparable (AG10008, 24.9%; RM7, 21%). However, the percentage agreement of identical staining intensities of positive cores was only 7%. In contrast, the percentage agreement of negative cores was 62.8%. In approximately 30% of the cores, the antibodies produced discordant staining intensities. Only one of the two antibody stainings (AG10008) conveyed prognostic information and was associated with a shorter progression-free patient survival. CONCLUSIONS: Our study underscores that nuclear AR-V7 expression can be detected in primary prostate cancer prior to long-term androgen deprivation and castration resistance. There are staining differences between the two antibodies in tumor tissue, for which we currently have no explanation. Clearly, improvements in the detection of functional AR-V7 in prostate cancer are urgently needed.
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