Antibody selection influences the detection of AR-V7 in primary prostate cancer

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.

Keywords: AR-V7; Prostate cancer.