Alternative HERPTENAkt Pathway Activation in HPV Positive and Negative Penile Carcinomas 英文参考文献.docVIP
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Alternative HERPTENAkt Pathway Activation in HPV Positive and Negative Penile Carcinomas 英文参考文献
AlternativeHER/PTEN/AktPathwayActivationinHPV
PositiveandNegativePenileCarcinomas
ElzbietaStankiewicz1*,DavidM.Prowse1,MansumNg1,JackCuzick2,DavidMesher2,FrancesHiscock1,
Yong-JieLu1,NicholasWatkin3,CatherineCorbishley4,WayneLam4,DanielM.Berney1
1CentreforMolecularOncologyandImaging,InstituteofCancer,BartsandTheLondonSchoolofMedicineandDentistry,QueenMaryUniversityofLondon,London,
UnitedKingdom,2CancerResearchUKCentreforEpidemiology,MathematicsandStatistics,WolfsonInstituteofPreventiveMedicine,BartsandTheLondonSchoolof
Medicine and Dentistry, London, Queen Mary University of London, United Kingdom, 3The Department of Urology, St George’s Hospital, Tooting, London, United
Kingdom,4TheCellularPathologyDepartment,StGeorge’sHospital,Tooting,London,UnitedKingdom
Abstract
Background: The pathogenesis of penile squamous cell carcinoma (PSCC) is not well understood, though risk factors
include human papillomavirus (HPV). Disruption of HER/PTEN/Akt pathway is present in many cancers; however there is
little information on its function in PSCC. We investigated HER family receptors and phosphatase and tension homolog
(PTEN)inHPV-positiveandnegativePSCCanditsimpactonAktactivationusingimmunohistochemistryandfluorescentin
situhybridisation(FISH).
Methodology/Principal Findings: 148 PSCCs were microarrayed and immunostained for phosphorylated EGFR (pEGFR),
HER2, HER3, HER4, phosphorylated Akt(pAkt), Akt1 and PTEN proteins. EGFR and PTEN gene status were alsoevaluated
usingFISH.HPVpresencewasassessedbyPCR.pEGFRexpressionwasdetectedsignificantlylessfrequentlyinHPV-positive
thanHPV-negativetumours(p=0.0143).Conversely,HER3expressionwassignificantlymorecommoninHPV-positivecases
(p=0.0128).HER4,pAkt,AktandPTENproteinexpressionwerenotrelatedtoHPV.HER3(p=0.0054)andHER4(p=0.0002)
receptors significantly correlated with cytoplasmic Akt1 immunostaining. All three proteins positively correlated with
tumourgrade(HER3,p=0.0029;HER4,p=0.0118;Akt1,p=0.0001).pEGFRexpressioncorrelatedwithpAktbut
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