Analytical Validation and Clinical Qualification of a New Immunohistochemical Assay for Androgen Receptor Splice Variant-7 Protein Expression in Metastatic Castration-resistant Prostate Cancer
| العنوان: | Analytical Validation and Clinical Qualification of a New Immunohistochemical Assay for Androgen Receptor Splice Variant-7 Protein Expression in Metastatic Castration-resistant Prostate Cancer |
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| المؤلفون: | Ruth Riisnaes, Adam Sharp, Zafeiris Zafeiriou, Jonathan Welti, Ines Figueiredo, David Lorente, Shihua H. Sun, Pasquale Rescigno, Johann S. de Bono, Stephen R. Plymate, Daniel Nava Rodrigues |
| المصدر: | EUROPEAN UROLOGY r-IIS La Fe. Repositorio Institucional de Producción Científica del Instituto de Investigación Sanitaria La Fe instname |
| بيانات النشر: | Elsevier BV, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Oncology, Time Factors, Biopsy, Treatment resistance, urologic and male genital diseases, Androgen receptor variant-7, chemistry.chemical_compound, Prostate cancer, 0302 clinical medicine, Protein Isoforms, Castration-resistant prostate cancer, Prostate, Antibodies, Monoclonal, Middle Aged, Prognosis, Immunohistochemistry, 3. Good health, Survival Rate, Prostatic Neoplasms, Castration-Resistant, Androgen receptor, Receptors, Androgen, 030220 oncology & carcinogenesis, Benzamides, Androstenes, PCA3, medicine.medical_specialty, Urology, Antineoplastic Agents, 03 medical and health sciences, Cell Line, Tumor, Internal medicine, Nitriles, Phenylthiohydantoin, medicine, Humans, Enzalutamide, splice, Aged, Retrospective Studies, Cell Nucleus, Predictor of outcome, business.industry, Metastatic biopsy, Androgen Receptor Splice Variant 7, medicine.disease, 030104 developmental biology, chemistry, Drug Resistance, Neoplasm, Cancer biomarkers, business |
| الوصف: | Background: The androgen receptor splice variant-7 (AR-V7) has been implicated in the development of castration-resistant prostate cancer (CRPC) and resistance to abiraterone and enzalutamide. Objective: To develop a validated assay for detection of AR-V7 protein in tumour tissue and determine its expression and clinical significance as patients progress from hormone -sensitive prostate cancer (HSPC) to CRPC. Design, setting, and participants: Following monoclonal antibody generation and validation, we retrospectively identified patients who had HSPC and CRPC tissue available for AR-V7 immunohistochemical (IHC) analysis. Outcome measurements and statistical analysis: Nuclear AR-V7 expression was determined using IHC H score (HS) data. The change in nuclear AR-V7 expression from HSPC to CRPC and the association between nuclear AR-V7 expression and overall survival (OS) was determined. Results and limitations: Nuclear AR-V7 expression was significantly lower in HSPC (median HS 50, interquartile range [IQR] 17.5-90) compared to CRPC (HS 135, IQR 80-157.5; p < 0.0001), and in biopsy tissue taken before (HS 80, IQR 30-136.3) compared to after (HS 140, IQR 105-167.5; p = 0.007) abiraterone or enzalutamide treatment. Lower nuclear AR-V7 expression at CRPC biopsy was associated with longer OS (hazard ratio 1.012, 95% confidence interval 1.004-1.020; p = 0.003). While this monoclonal antibody primarily binds to AR-V7 in PC biopsy tissue, it may also bind to other proteins. Conclusions: We provide the first evidence that nuclear AR-V7 expression increases with emerging CRPC and is prognostic for OS, unlike antibody staining for the AR N terminal domain. These data indicate that AR-V7 is important in CRPC disease biology; agents targeting AR splice variants are needed to test this hypothesis and further improve patient outcome from CRPC. Patient summary: In this study we found that levels of the protein AR-V7 were higher in patients with advanced prostate cancer. A higher level of AR-V7 identifies a group of patients who respond less well to certain prostate cancer treatments and live for a shorter period of time. (C) 2016 European Association of Urology. Published by Elsevier B.V. |
| تدمد: | 0302-2838 |
| DOI: | 10.1016/j.eururo.2016.03.049 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4314bcc2ef0695fe34984c5893390ead https://doi.org/10.1016/j.eururo.2016.03.049 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....4314bcc2ef0695fe34984c5893390ead |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 03022838 |
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| DOI: | 10.1016/j.eururo.2016.03.049 |