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dc.contributor.authorWelti, J
dc.contributor.authorRodrigues, DN
dc.contributor.authorSharp, A
dc.contributor.authorSun, S
dc.contributor.authorLorente, D
dc.contributor.authorRiisnaes, R
dc.contributor.authorFigueiredo, I
dc.contributor.authorZafeiriou, Z
dc.contributor.authorRescigno, P
dc.contributor.authorde Bono, JS
dc.contributor.authorPlymate, SR
dc.date.accessioned2016-09-05T13:29:28Z
dc.date.issued2016-10
dc.identifier.citationEuropean urology, 2016, 70 (4), pp. 599 - 608
dc.identifier.issn0302-2838
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/101
dc.identifier.eissn1873-7560
dc.identifier.doi10.1016/j.eururo.2016.03.049
dc.description.abstractBackground 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.formatPrint-Electronic
dc.format.extent599 - 608
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0
dc.subjectProstate
dc.subjectCell Line, Tumor
dc.subjectCell Nucleus
dc.subjectHumans
dc.subjectPhenylthiohydantoin
dc.subjectAndrostenes
dc.subjectProtein Isoforms
dc.subjectReceptors, Androgen
dc.subjectAntineoplastic Agents
dc.subjectAntibodies, Monoclonal
dc.subjectBiopsy
dc.subjectPrognosis
dc.subjectImmunohistochemistry
dc.subjectSurvival Rate
dc.subjectRetrospective Studies
dc.subjectDrug Resistance, Neoplasm
dc.subjectTime Factors
dc.subjectAged
dc.subjectMiddle Aged
dc.subjectMale
dc.subjectProstatic Neoplasms, Castration-Resistant
dc.titleAnalytical Validation and Clinical Qualification of a New Immunohistochemical Assay for Androgen Receptor Splice Variant-7 Protein Expression in Metastatic Castration-resistant Prostate Cancer.
dc.typeJournal Article
dcterms.dateAccepted2016-03-31
rioxxterms.versionofrecord10.1016/j.eururo.2016.03.049
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by-nc-nd/4.0
rioxxterms.licenseref.startdate2016-10
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfEuropean urology
pubs.issue4
pubs.notesNot 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-statusPublished
pubs.volume70
pubs.embargo.termsNot known
icr.researchteamProstate Cancer Targeted Therapy Groupen_US
icr.researchteamTranslational Therapeuticsen_US
dc.contributor.icrauthorRescigno, Pasqualeen
dc.contributor.icrauthorSharp, Adamen
dc.contributor.icrauthorDe Bono, Johannen


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