Primary Human Ovarian Epithelial Cancer Cells Broadly Express HER2 at Immunologically-Detectable Levels 英文参考文献.docVIP

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Primary Human Ovarian Epithelial Cancer Cells Broadly Express HER2 at Immunologically-Detectable Levels 英文参考文献.doc

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Primary Human Ovarian Epithelial Cancer Cells Broadly Express HER2 at Immunologically-Detectable Levels 英文参考文献

PrimaryHumanOvarianEpithelialCancerCellsBroadly ExpressHER2atImmunologically-DetectableLevels EvripidisLanitis1,2,DenardaDangaj1,2,IanS.Hagemann3,De-GangSong1,AndrewBest1, RaphaelSandaltzopoulos2,GeorgeCoukos1,DanielJ.Powell,Jr.1,3* 1Ovarian Cancer Research Center, Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America, 2DepartmentofMolecularBiologyandGenetics,DemocritusUniversityofThrace,Alexandroupolis,Greece,3AbramsonCancerCenter,DepartmentofPathologyand LaboratoryMedicine,UniversityofPennsylvania,Philadelphia,Pennsylvania,UnitedStatesofAmerica Abstract ThebreadthofHER2expressionbyprimaryhumanovariancancersremainscontroversial,whichquestionsitssuitabilityasa universalantigeninthismalignancy.Toaddresstheseissues,weperformedextensiveHER2expressionanalysisonawide panel of primary tumors as well as established and short-term human ovarian cancer cell lines. Conventional immunohistochemical(IHC)analysisofmultipletumorsitesin50casesofhigh-gradeovarianserouscarcinomasrevealed HER2 overexpression in 29% of evaluated sites. However, more sensitive detection methods including flow cytometry, western blot analysis and q-PCR revealed HER2 expression in all fresh tumor cells derived from primary ascites or solid tumorsaswellasallestablishedandshort-termculturedcancercelllines.CancercellsgenerallyexpressedHER2athigher levelsthanthatfoundinnormalovariansurface epithelial(OSE)cells.Accordingly, genetically-engineeredhumanTcells expressing an HER2-specific chimeric antigen receptor (CAR) recognized and reacted against all established or primary ovariancancercellstestedwithminimalornoreactivityagainstnormalOSEcells.Inconclusion,allhumanovariancancers expressimmunologically-detectablelevelsofHER2,indicatingthatIHCmeasurementunderestimatesthetruefrequencyof HER2-expressingovariancancersandmaylimitpatientaccesstootherwiseclinicallymeaningfulHER2-targetedtherapies. Citation: Lanitis E, Dangaj D, Hagemann IS, S