Abstract 781: Comparative analysis of androgen receptor phosphorylation in castrate resistant prostate cancer using conventional immunohistochemistry and immunofluorescence

Abstract

Abstract Despite the increase in new hormonal therapies available to treat prostate cancer, over 10,000 men die per year in the UK from treatment resistant disease, therefore highlighting the need to develop effect predictive and prognostic markers for these patients. Therefore, we aim to identify the most accurate method of determining the association of androgen dependent (pARser81) and androgen independent (pARser213) phosphorylation with patient survival. 109 patients with castrate resistant prostate cancer were immunohistochemically characterised for pARser81 and pARser213 expression to determine the association of androgen receptor phosphorylation with time to death from biochemical relapse. Immunofluorescence was employed on formalin fixed paraffin embedded tissue to determine the localisation of pARser81 and pARser213 and whether phosphorylation of the AR at these sites were occurring within the same cell or neighbouring cells. High pARser213 immunoreactivity was associated with a reduced time to death from biochemical relapse when compared to those with low pARser213 expression (p=0.001). However pARser81 expression was not associated with survival (p=0.068). Patients expressing both high pARser81 and high pARser213 had a reduced time to death from biochemical relapse when compared to those with low expression of one or both sites (p=0.000297). A subgroup of these patients were then selected and dual immunofluorescence employed to assess pARser81 and pARser213 expression. The presence of pARser81 expression within the nucleus reduced time to death from biochemical relapse when compared to those with no pARser81 nuclear expression (p=0.029). Punctate nuclear pARser81 expression (which was not observed using standard immunohistochemistry) was also associated with reduced time to death from biochemical relapse when compared to those with no pARser81 expression (p=0.008). pARser213 nuclear expression was associated with reduced time to death to death from biochemical relapse when compared to those with no pARser213 expression (p=0.000082). When dual immunofluorescence was employed, expression of both pARser81 and pARser213 within the nucleus of the same cell was associated with reduced time to death from biochemical relapse when compared to those with no expression of either sites (p=0.00003). In conclusion, dual expression of pARser81 and pARser213 are associated with reduced time to death from relapse using either immunohistochemistry or immunofluorescence. However immunofluorescence appears to be more precise, identifying the importance of pARser81 expression in castrate resistant patients that would otherwise of been missed via traditional immunohistochemistry along with highlighted the importance of personalised medicine in prostate cancer with the potential of dual targeting patients. Citation Format: Milly McAllister, Pamela McCall, Mark Underwood, Hing Leung, Joanne Edwards. Comparative analysis of androgen receptor phosphorylation in castrate resistant prostate cancer using conventional immunohistochemistry and immunofluorescence [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 781.