OBJECTIVE: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.
OBJECTIVE: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Authors: Ankur Sharma; Wen-Shuz Yeow; Adam Ertel; Ilsa Coleman; Nigel Clegg; Chellappagounder Thangavel; Colm Morrissey; Xiaotun Zhang; Clay E S Comstock; Agnieszka K Witkiewicz; Leonard Gomella; Erik S Knudsen; Peter S Nelson; Karen E Knudsen Journal: J Clin Invest Date: 2010-11-22 Impact factor: 14.808
Authors: Russell Z Szmulewitz; Elizabeth Chung; Hikmat Al-Ahmadie; Silver Daniel; Masha Kocherginsky; Aria Razmaria; Gregory P Zagaja; Charles B Brendler; Walter M Stadler; Suzanne D Conzen Journal: Prostate Date: 2011-05-11 Impact factor: 4.104
Authors: Randy S Schrecengost; Jeffry L Dean; Jonathan F Goodwin; Matthew J Schiewer; Mark W Urban; Timothy J Stanek; Robyn T Sussman; Jessica L Hicks; Ruth C Birbe; Rossitza A Draganova-Tacheva; Tapio Visakorpi; Angelo M DeMarzo; Steven B McMahon; Karen E Knudsen Journal: Cancer Res Date: 2013-11-06 Impact factor: 12.701