dc.contributor.author | Welti, J | |
dc.contributor.author | Rodrigues, DN | |
dc.contributor.author | Sharp, A | |
dc.contributor.author | Sun, S | |
dc.contributor.author | Lorente, D | |
dc.contributor.author | Riisnaes, R | |
dc.contributor.author | Figueiredo, I | |
dc.contributor.author | Zafeiriou, Z | |
dc.contributor.author | Rescigno, P | |
dc.contributor.author | de Bono, JS | |
dc.contributor.author | Plymate, SR | |
dc.date.accessioned | 2016-09-05T13:29:28Z | |
dc.date.issued | 2016-10 | |
dc.identifier.citation | European urology, 2016, 70 (4), pp. 599 - 608 | |
dc.identifier.issn | 0302-2838 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/101 | |
dc.identifier.eissn | 1873-7560 | |
dc.identifier.doi | 10.1016/j.eururo.2016.03.049 | |
dc.description.abstract | 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. | |
dc.format | Print-Electronic | |
dc.format.extent | 599 - 608 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0 | |
dc.subject | Prostate | |
dc.subject | Cell Line, Tumor | |
dc.subject | Cell Nucleus | |
dc.subject | Humans | |
dc.subject | Phenylthiohydantoin | |
dc.subject | Androstenes | |
dc.subject | Protein Isoforms | |
dc.subject | Receptors, Androgen | |
dc.subject | Antineoplastic Agents | |
dc.subject | Antibodies, Monoclonal | |
dc.subject | Biopsy | |
dc.subject | Prognosis | |
dc.subject | Immunohistochemistry | |
dc.subject | Survival Rate | |
dc.subject | Retrospective Studies | |
dc.subject | Drug Resistance, Neoplasm | |
dc.subject | Time Factors | |
dc.subject | Aged | |
dc.subject | Middle Aged | |
dc.subject | Male | |
dc.subject | Prostatic Neoplasms, Castration-Resistant | |
dc.title | Analytical Validation and Clinical Qualification of a New Immunohistochemical Assay for Androgen Receptor Splice Variant-7 Protein Expression in Metastatic Castration-resistant Prostate Cancer. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2016-03-31 | |
rioxxterms.versionofrecord | 10.1016/j.eururo.2016.03.049 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by-nc-nd/4.0 | |
rioxxterms.licenseref.startdate | 2016-10 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | European urology | |
pubs.issue | 4 | |
pubs.notes | Not known | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Prostate Cancer Targeted Therapy Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Translational Therapeutics | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Prostate Cancer Targeted Therapy Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Translational Therapeutics | |
pubs.publication-status | Published | |
pubs.volume | 70 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Prostate Cancer Targeted Therapy Group | en_US |
icr.researchteam | Translational Therapeutics | en_US |
dc.contributor.icrauthor | Rescigno, Pasquale | en |
dc.contributor.icrauthor | Sharp, Adam | en |
dc.contributor.icrauthor | De Bono, Johann | en |