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RESEARCH PRODUCT
AR-V7 Protein Expression in Circulating Tumour Cells Is Not Predictive of Treatment Response in mCRPC
Holger H.h. ErbTamara DiehlGustavo B. BarettonEva JüngelManuela Hemmerlein-thomasPeter SparwasserIgor TsaurAndreas NeisiusChristian ThomasUlrich SommerAxel Haferkampsubject
MaleUrology030232 urology & nephrologyAntineoplastic AgentsDocetaxel03 medical and health scienceschemistry.chemical_compoundProstate cancer0302 clinical medicineCell Line TumormedicineHumansEnzalutamideProspective StudiesLiquid biopsyAgedAged 80 and overbusiness.industryAndrogen AntagonistsNeoplastic Cells CirculatingPrognosismedicine.diseaseAndrogen receptorProstatic Neoplasms Castration-ResistantTreatment OutcomeDocetaxelchemistryReceptors AndrogenCabazitaxel030220 oncology & carcinogenesisCancer researchBiomarker (medicine)ImmunohistochemistryTaxoidsbusinessmedicine.drugdescription
<b><i>Introduction:</i></b> 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. <b><i>Methods:</i></b> CTCs were isolated by cell separation by density gradient centrifugation from patients with metastatic CRPC (<i>n</i> = 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. <b><i>Results:</i></b> 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. <b><i>Discussion/Conclusion:</i></b> 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.
year | journal | country | edition | language |
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2019-07-04 | Urologia Internationalis |