Acentralprobleminovariancancerislatediagnosiswhenthe5-yearsurvivalrateplummetstolessthan50%.Ovariancancersymptomsarevagueandnonspecificandscreeningisnotgenerallyeffective.Becauseovariancancerissodeadlyprophylacticbilateralsalpingo-oophorectomy(BSO)isoftenrecommendedforwomenathighriskhoweverBSOhasfertilityandhealthconsequences.Alsoforalargenumberofwomenatelevatedbutnotextremelyhighriskthebestpreventionaction-atthebesttime-isunclear.Itisnowbelievedthatdeadlyovariancancermayactuallystartinthefallopiantubes(FTs)andthatprecancerouscellsmightbedetectablebeforetheyspreadtotheovary.TheFTscanbeexaminedbypassingathinfalloposcopethroughahysteroscopeandtheostiaoftheFT.Ourlong-termgoalistocreateaneffectiveminimal-invasiveandclinicallyreliablemethodtoassessawomansFThealthincludingdetectingtheearliestpre-cancerousabnormalitiestoguideaphysiciansandpatientschoiceofappropriatepreventionortreatmentmethods.Detectingsmallpremalignantlesionsischallengingandwewillemploythreecomplimentarytechniqueswithpromiseforthistask.Thefirstismultispectralfluorescenceimaging(MFI)whichhaspreviouslybeenshowntodifferentiatenormalfromcanceroustissueintheovariesandFT.Thisinstantaneousintacttissuemodalitywillbecombinedwithtwoexvivocellularanalysistechniquesknowntobesensitivetosubtlepre-cancerouschanges.FirstReversePhaseProteinMicroarray(RPPA)measuresfunctionalcellularproteinsinmicroscopicquantitiesofcellsincludinganumberofkeysignalingandbiochemicaleventsthatareknownmediatorsofcanceroustransformation.Secondkaryometryorcomputer-aidedchromatinpatternanalysishasbeenshowninseveralorganstocorrelatewithpresenceofearlydiseaseandriskofprogressiontoinvasivecancer.IthasalsoshownnormalizationofovaryandFTtissueafterchemopreventionandhasrevealedthepresenceofastrongfieldeffectinmanyorgansortheabilitytosenseacancerouslesionseveralcentimetersawayfromthecellcollectionsite.TheoverallgoalofthisprojectistoshowproofofprincipleofacombinedmethodfordifferentiatingFTsamplesfromnormalriskhighriskandovariancancerpatientsandtodevelopamethodthatcanbeusedtocollectingadequateFTcellsforanalysis.Thespecificaimsare:Aim1.Examinetissue-bankedandnewly-collectedhistologicalsectionsofFTswithfluorescenceimagingRPPAandkaryometrytodevelopanintegratedalgorithmthatstratifiespatientsbasedonpresenceofdiseaseandasafunctionofknownpatientriskstatus.ExaminethealgorithmasafunctionofspatiallocationintheFT.Aim2:DevelopafalloposcopecontaininganimagingchannelfornavigationandMFIcapabilityaswellasacellsamplingchannel.ExamineaspirationandwirescrapeoptionsfortheirabilitytocollectadequatecellsforRPPAandkaryometryanalysis.