AZGP1 Protein Expression in Hormone-Naïve Advanced Prostate Cancer Treated with Primary Androgen Deprivation Therapy.

Mads Dochedahl Winther,Kasper Drimer Berg,Martin Andreas Røder,Birgitte Grønkær Toft,Gitte Kristensen,Klaus Brasso,James D Brooks,Hein Vincent Stroomberg

doi:10.3390/diagnostics10080520

Mads Dochedahl Winther, Kasper Drimer Berg + Show 6 more

Open Access

https://doi.org/10.3390/diagnostics10080520

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Abstract

Biomarkers for predicting the risk of castration-resistant prostate cancer (CRPC) in men treated with primary androgen deprivation therapy (ADT) are lacking. We investigated whether Zinc-alpha 2 glycoprotein (AZGP1) expression in the diagnostic biopsies of men with hormone-naïve prostate cancer (PCa) undergoing primary ADT was predictive of the development of CRPC and PCa-specific mortality. The study included 191 patients who commenced ADT from 2000 to 2011. The AZGP1 expression was evaluated using immunohistochemistry and scored as high or low expression. The risks of CRPC and PCa-specific mortality were analyzed using stratified cumulative incidences and a cause-specific COX regression analysis for competing risk assessment. The median follow-up time was 9.8 (IQR: 6.1–12.7) years. In total, 94 and 97 patients presented with low and high AZGP1 expression, respectively. A low AZGP1 expression was found to be associated with a shorter time to CRPC when compared to patients with a high AZGP1 expression (HR: 1.5; 95% CI: 1.0–2.1; p = 0.03). However, the multivariable analysis demonstrated no added benefit by adding the AZGP1 expression to prediction models for CRPC. No differences for PCa-specific mortality between the AZGP1 groups were observed. In conclusion, a low AZGP1 expression was associated with a shorter time to CRPC for PCa patients treated with first-line ADT but did not add any predictive information besides well-established clinicopathological variables.

Highlights

Advanced and metastatic prostate cancer (PCa) at the time of diagnosis is associated with a high risk of morbidity and mortality
Even though PCa initially responds to androgen deprivation therapy (ADT), the majority of men managed on ADT will eventually progress to castration-resistant prostate cancer (CRPC) [5,6]
We investigated the predictive value of AZGP1, which was assessed by applying IHC to tumor tissue samples from men with locally advanced or metastatic PCa commencing

Summary

Introduction

Advanced and metastatic prostate cancer (PCa) at the time of diagnosis is associated with a high risk of morbidity and mortality. Recent data suggest that de novo metastatic PCa accounts for more than 60% of men eventually dying from the disease [1]. Even though PCa initially responds to ADT, the majority of men managed on ADT will eventually progress to castration-resistant prostate cancer (CRPC) [5,6]. For these men, the prognosis is grave, Diagnostics 2020, 10, 520; doi:10.3390/diagnostics10080520 www.mdpi.com/journal/diagnostics

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