Academic Journal
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: | Welti, J, Rodrigues, DN, Sharp, A, Sun, S, Lorente, D, Riisnaes, R, Figueiredo, I, Zafeiriou, Z, Rescigno, P, de Bono, JS, Plymate, SR |
| المساهمون: | Sharp, Adam, Rescigno, Pasquale, De Bono, Johann |
| بيانات النشر: | ELSEVIER SCIENCE BV |
| سنة النشر: | 2017 |
| المجموعة: | The Institute of Cancer Research (ICR): Publications Repository |
| مصطلحات موضوعية: | Androgen receptor, Androgen receptor variant-7, Castration-resistant prostate cancer, Metastatic biopsy, Treatment resistance, Predictor of outcome |
| 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 ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | 608; application/pdf |
| اللغة: | English |
| تدمد: | 0302-2838 1873-7560 |
| Relation: | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000385503700013&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=d4b848928d1c3e5c86d298abb68475f9; EUROPEAN UROLOGY, 2016, 70 (4), pp. 599 - 608; https://repository.icr.ac.uk/handle/internal/375 |
| DOI: | 10.1016/j.eururo.2016.03.049 |
| الاتاحة: | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000385503700013&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=d4b848928d1c3e5c86d298abb68475f9 https://repository.icr.ac.uk/handle/internal/375 https://doi.org/10.1016/j.eururo.2016.03.049 |
| رقم الانضمام: | edsbas.7C2299CC |
| قاعدة البيانات: | BASE |
| تدمد: | 03022838 18737560 |
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| DOI: | 10.1016/j.eururo.2016.03.049 |