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AR-V7 Protein Expression in Circulating Tumour Cells Is Not Predictive of Treatment Response in mCRPC

Authors :
Holger H.H. Erb
Tamara Diehl
Gustavo B. Baretton
Eva Jüngel
Manuela Hemmerlein-Thomas
Peter Sparwasser
Igor Tsaur
Andreas Neisius
Christian Thomas
Ulrich Sommer
Axel Haferkamp
Source :
Urologia Internationalis. 104:253-262
Publication Year :
2020
Publisher :
S. Karger AG, 2020.

Abstract

Introduction: Androgen receptor variant 7 (AR-V7) plays an important role in the progression of castration-resistant prostate cancer (CRPC) and has shown potential as a predictive biomarker in circulating tumour cells (CTCs) isolated from the bloodstream in terms of a liquid biopsy. Studies have shown that AR-V7 is a potential surrogate for selecting drug classes for systemic treatment by detecting nuclear AR-V7 by immunofluorescence or measuring AR-V7 messenger RNA by quantitative PCR. Here, we assessed the predictive value of AR-V7 detected by classical immunohistochemistry (IHC) for treatment response. Methods: CTCs were isolated by cell separation by density gradient centrifugation from patients with metastatic CRPC (n = 26) before, while, and after undergoing a new therapy with chemotherapy (cabazitaxel or docetaxel) or antiandrogen (enzalutamide or abiraterone). CTCs were sequentially cytospun on object slides, and AR-V7 status was then detected by IHC based on a staining regime established on a 22Rv1 cell line with antibodies against CK8/18 und AR-V7. Results: AR-V7 status detected by IHC showed no predictive value for progression-free survival (PFS). Kaplan-Meier analysis revealed that there was no difference in PFS between patients found positive or negative for AR-V7. Discussion/Conclusion: AR-V7 detected by classical IHC has no predictive value for treatment response in the described setting. The future role of AR-V7 in CTCs as a biomarker in clinical routine remains elusive.

Details

ISSN :
14230399 and 00421138
Volume :
104
Database :
OpenAIRE
Journal :
Urologia Internationalis
Accession number :
edsair.doi.dedup.....0d30797bcbf86941081a1985f292dab4
Full Text :
https://doi.org/10.1159/000504416