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.doc

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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