Androgen receptor expression is associated with prostate cancer‐specific survival in castrate patients with metastatic disease

Abstract

To investigate whether baseline (before treatment) clinical variables and tumour specimen characteristics (including the androgen receptor, AR) from patients with castrate-resistant metastatic prostate cancer can be used to predict the time to prostate cancer-specific mortality and overall survival, as AR levels in prostate cancer have been associated with disease progression, including prostate-specific antigen (PSA) recurrence and systemic metastasis. Haematoxylin and eosin (H&E) slides/blocks and outcome data from a 104 castrate patients with metastatic disease (43 prostatectomy and 61 prostate needle biopsy samples), were independently reviewed; H&E morphometry and quantitative immunofluorescence were used to assess the samples. Sections were analysed with a multiplex quantitative immunofluorescence (IF) assay for cytokeratin-18 (epithelial cells), 4',6-diamidino-2-phenylindole (nuclei), p63/high molecular weight keratin (basal cells), AR and alpha-methyl CoA-racemase. Images were acquired with spectral imaging software and processed for quantification with IF algorithms. The median follow-up was 12 years from diagnosis; 49 men (47%) baseline PSA levels of > or = 20 ng/mL, 55 (53%) had a Gleason sum of 8, 63 (60%) died from the disease and 40% were alive (censored). In all, 66 patients had evaluable IF features, and the association with outcome was evaluated by univariate Cox modelling and support-vector regression. PSA was the only clinical variable associated with outcome (concordance index, CoI, 0.41; P < 0.05, log-rank test). The amount of AR present within tumour nuclei (regardless of tissue provenance and primary treatment) significantly correlated with a greater risk of a shorter time to prostate cancer-specific mortality (CoI 0.36; P < 0.05 log-rank test). There were no H&E features that correlated with mortality. By univariate analysis, increased nuclear AR expression in either the diagnostic biopsy and/or radical prostatectomy specimen, from patients with advanced disease, was associated with a reduced time to prostate cancer-specific mortality.