AR-V7 Protein Expression in Circulating Tumour Cells Is Not Predictive of Treatment Response in mCRPC
Autor: | 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 |
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Rok vydání: | 2020 |
Předmět: |
Male
Urology 030232 urology & nephrology Antineoplastic Agents Docetaxel 03 medical and health sciences chemistry.chemical_compound Prostate cancer 0302 clinical medicine Cell Line Tumor medicine Humans Enzalutamide Prospective Studies Liquid biopsy Aged Aged 80 and over business.industry Androgen Antagonists Neoplastic Cells Circulating Prognosis medicine.disease Androgen receptor Prostatic Neoplasms Castration-Resistant Treatment Outcome chemistry Receptors Androgen Cabazitaxel 030220 oncology & carcinogenesis Cancer research Biomarker (medicine) Immunohistochemistry Taxoids business medicine.drug |
Zdroj: | Urologia Internationalis. 104:253-262 |
ISSN: | 1423-0399 0042-1138 |
DOI: | 10.1159/000504416 |
Popis: | 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. |
Databáze: | OpenAIRE |
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