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1、Biomarkersontumortissue:fromresearchtodiagnostictoolsusedintheClinicBernardTtuMDProfessorofPathologyLavalUniversityConflictofinterestCurrentlynoconflictofinteresttodeclare.IhavebeenconsultantforDiagnocureuntil2009BiomarkerGutmanetal.Naturereviews/cancer2006;6:565-571Definition:Anymeasurablediagnosti
2、cindicatorthatisusedtoassesstheriskorpresenceofdisease.FDA(diagnostic):determiningfutureriskofdiseasescreeningfordiseaseconfirmingpresenceofdiseasedeterminingprognosisorstagingmonitoringand/oroptimizingtreatmentoutcomesdrugresponsetoxicreactiontodrugsPersonalizedmedicineBiomarkersareexpectedtoplayan
3、increasinglyimportantroleCaresmustbeefficient,safe,costeffectiveintegrationofpharmaceuticalanddiagnosticactivitiesareexpectedtoincreaseWeexpectmoreteststobeperformedbyIHCinpathologylaboratoriesbecauseofeaseandlowcostMedicalproductdevelopmentCanada:HealthCanadaQubec:ConseildumdicamentTestsinpathology
4、Ontario:QMP-LS/CCOQubec:?IntroductionofnewtestsontumortissueinpathologyManynewtestsareexpectedinthenearfuturePathologylaboratoriesareincreasinglyinvolvedWhichlaboratoryshoulddothetest?:Anylaboratoryinterestedatdevelopingnewtests?Manufacturerswhichdevelopedthetest?Ministryofhealth?Historyofimmunohist
5、ochemistryEarly1980s:firstantibodiesforclinicaluse1980-2000:antibodiesmostlydiagnosticorprognosticER/PRpredictive2000-:FDA32GenomicBiomarkersintheContextofApprovedDrugLabelsMarkersontumortissueinpathology:HER2/neuEGFRKITKRASImmunohistochemistryTypeI:anytestperformedtodeterminecelldifferentiationandu
6、sedfordiagnosticpurposes(mostantibodies)TypeII:testsnotrelatedtomorphologyandusedforprognosticandpredictivepurposes(HER2/neu,ER/PR)ForresearchuseonlyRpertoirequbcoisetsystmedemesuredesprocduresdebiologiemdicaleRpertoirequbcoisetsystmedemesuredesprocduresdebiologiemdicaleRpertoirequbcoisetsystmedemes
7、uredesprocduresdebiologiemdicaleMarkertestinginQubecin200958pathologylaboratories37ER/PRbyIHC21HER2/neubyIHC5HER2byFISHENSURING ACCESS TO HIGH QUALITY MOLECULAR ONCOLOGY LABORATORY TESTING AND CLINICALCANCER GENETIC SERVICES IN ONTARIO / ReportoftheMolecularOncologyTaskForce|December2008Recommendati
8、ons:2)ImplementamandatoryapprovalprocessforeachgenetictestperformedbylaboratoriesinOntarioandadministeredbytheappropriateregulatoryagenciestoensurethatonlyappropriatelyaccreditedandlicensedlaboratorieswithcredentialedpersonnelarereportingandinterpretinglaboratoryresultsthatimpactpatientcare.Thefollo
9、wingstepsoutlinetheTaskForcesproposedprocessforbringingnewtestsintoclinicalservice.VI.TheMinistrysetsareimbursementrateforthetestandrelatedclinicalservices.6)Promotetranslationalresearchandestablishan“advancenotice”processtoensurethesystemispreparedtoimplementnewtestsandtechnologieswhenevidencewarra
10、nts.CancerCareOntarioHER2/neutestinginOntariooverseenbyQMP-LS/CCO($pertest)18HER2/neubyIHC2HER2byFISH9 testing sites9 testing sitesMount Sinai HospitalQA Ref. centre/Advanced testing centreSunnybrook & WomensQA Ref. centre/Advanced testing centreNew siteNew siteMOH & CCOASCO-CAPrecommendations2007Ca
11、nadianconsensusonHER2/neutesting,2007ASCO-CAPCanadian consensusASCO-CAPrecommendations2007ReproducibilityHER2testingPaiketal,JNatCancerInst94:852-854,2002NSABPLocal laboratory% Concordance positive casesTotal79%smallvolume(100/month)76%Largevolume97%CEPO(ComitdelvolutiondesPratiquesenOncologie)recom
12、mendations,2005useoftrastuzumabfortheadjuvanttreatmentofinvasivebreastcancers.implementation of a quality assurance program to insure reliable HER2/neu testing in pathology laboratories.AETMIS(AgencedvaluationdesTechnologiesetdesModesdInterventionenSant)Diagnostic Performance of Techniques Used for
13、HER-2 Testing in Breast CancerrecommendstheimplementationofanHER-2qualityassuranceprograminQuebecAtleastonereferencelabInternalandexternalqualitycontrolsAffiliationofeverylabtoareferencelabMinimum250casesannuallyOngoingtrainingforpathologistsandlabpersonnelCentraldatabaseforevaluationChallengesforQu
14、alityassuranceinanatomicpathologyinQuebecLittlehierarchyinserviceorganisationinpathologyParticipationtoproficiencytestingnotuniformuntilrecentlyManyauthoritiesinvolvedMinistryofHealthINSPQ/LSPQ(publichealth)ExpertcommitteesComitconsultatifenanatomopathologie(advisorycommittee)Comitdassurancequaliten
15、pathologie(LSPQ)Professionalassociations(pathology,microbiology,biochemistryetc)Comitconsultatifenanatomopathologie(advisory committee in anatomic pathology)Createdbythe“DirectiondelaLutteContreleCancer”insummer2008followingthepublicationofAETMISreportMandateIdentifycurrentpathologychallengesandreco
16、mmendspecificactionsDevelop a quality assurance program for pathology and recommend actions for quality improvementStandardizepathologyreportsforcancerProposesolutionstoovercomestaffshortageinpathologyComitconsultatifenanatomopathologie(advisory committee in anatomic pathology)AtministerBolducsreque
17、st,workonqualityassurancewasprioritizedTheGlobal plan for quality assurance in anatomic pathologywascompletedinOctober200916expertswereconsultedItwasendorsedbytheQuebeccollegeofphysiciansandtheQuebecassociationofpathologistsMinistryofHealthcommitteditselftoimplementthequalityassuranceprograminQubecG
18、lobalplanforqualityassuranceThreemajorObjectives1.CommitmentoftheMinistryofHealth2.Theprogrammustbemandatory3.TheprogrammustbeeducationalGlobalplanforqualityassurance20recommendationsItemscovered:InternalqualitycontrolProficiencytesting(externalqualityassurance)LaboratorydesignationSupportEvaluation
19、GlobalplanforqualityassuranceInternalqualitycontrolDevelopmentofguidelinesofgoodpracticeineverylaboratoryTissuepreparationandfixationTechniquevalidationandstandardizationUseofpositiveandnegativecontrolsInterpretationQualityindicatorsGlobalplanforqualityassuranceProficiencytestingMandatoryparticipati
20、ontoanexternalqualityassuranceprogramProgramdevelopmentundertheresponsibilityofthe“Comitdassurancequalitexterneenpathologie”(LSPQ)Preanalytic,analyticandpostanalyticphasesevaluatedConfidentialSupportgiventolaboratoriesexperiencingdifficultiesProgressiveimplementationStartedinFall2010Globalplanforqua
21、lityassuranceLaboratorydesignationAccordingtothelevelofcomplexityofanalysesAccordingtoonsiteexpertiseSpecifictotumoursiteRelatedtothepresenceofacancerinterdisciplinaryteamDevelopmentofaccreditationstandardsspecifictopathologyDesignationunderresponsibilityofanotherdirectionatMSSSGlobalplanforqualitya
22、ssuranceSupportContinuingtraining(APQ,OPTMQ)ExpertteamsinchargeofaccompanyinglabsexperiencingdifficultiesDevelopmentofguidelinesandprotocols(Breastcancer,coloncancer)DevelopmentofqualityindicatorsPrioritizationofthereplacementoflabequipmentGlobalplanforqualityassuranceProgramevaluationImplementation
23、ImprovementofqualityassurancefollowingimplementationIntroductionofnewtestsontumortissueinpathologyManynewtestsareexpectedinthenearfuturePathologylaboratoriesareincreasinglyinvolvedWhichlaboratoryshoulddothetest?:Anylaboratoryinterestedatdevelopingnewtests?Manufacturerswhichdevelopedthetest?Ministryofhealth?ConclusionsandfuturedirectionThereisaneedtoanticipatenewdiagnostictestsontumortissueScientificwatchtoidentifypotentialnewtests(“advancenotice”)ExpertsshouldbeaskedtorecommendreferencelabsCoordinationwithDLCCandMSSS
