Androgen receptor expression is associated with prostate cancer-specific survival in castrate patients with metastatic disease Journal Article
| Authors: | Donovan, M. J.; Osman, I.; Khan, F. M.; Vengrenyuk, Y.; Capodieci, P.; Koscuiszka, M.; Anand, A.; Cordon-Cardo, C.; Costa, J.; Scher, H. I. |
| Article Title: | Androgen receptor expression is associated with prostate cancer-specific survival in castrate patients with metastatic disease |
| Abstract: | Study Type - Aetiology (case series) Level of Evidence 4 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 α-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 ≥ 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. © 2009 AUREON LABORATORIES. |
| Keywords: | adult; cancer survival; human tissue; aged; middle aged; survival rate; human cell; major clinical study; overall survival; follow up; prostate specific antigen; metastasis; neoplasm proteins; risk factor; cancer mortality; time factors; prostate cancer; gleason score; prostatic neoplasms; survival time; prostatectomy; needle biopsy; prostate biopsy; epidemiologic methods; progression; neoplasm metastasis; androgen receptor; protein p63; cell nucleus; orchiectomy; receptors, androgen; androgens; neoplasms, hormone-dependent; cytokeratin 18; systems pathology; keratin; castrated male |
| Journal Title: | BJU International |
| Volume: | 105 |
| Issue: | 4 |
| ISSN: | 1464-4096 |
| Publisher: | Wiley Blackwell |
| Date Published: | 2010-02-01 |
| Start Page: | 462 |
| End Page: | 467 |
| Language: | English |
| DOI: | 10.1111/j.1464-410X.2009.08747.x |
| PUBMED: | 19624594 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 4" - "Export Date: 20 April 2011" - "CODEN: BJINF" - "Source: Scopus" |
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