小细胞肺癌诊断治疗进展r

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1、SmallCellLungCancer(SCLC):Diagnosis,TreatmentandNaturalHistoryGaryL.WeinsteinM.D.SCLCLungcancerepidemiologySCLCPathologyTumormarkersGeneticsClinicalcourseStagingTreatmentSCLC,factoids15–25%ofalllungcancersAlmostexclusivelyinsmokersDistinguishedfromNSCLCby:RapiddoublingtimeHighgrowt

2、hfractionEarlydevelopmentofwide-spreadmetsSCLC,factoids(cont’d)Consideredhighlyresponsiveto“chemsandbeams”BUT…usuallyrelapseswithin2yearsdespitetreatmentOverall,only3–8%ofallpatientssurvivemorethan5yearsMostcommonmalignancyassociatedwithNeurologicparaneoplasticsyndromesSCLC,patholog

3、yMostrecent(1999)WHOclassificationClassicalsmallcellcarcinomaLargecellneuroendocrinecancerCombinedsmallcellcarcinomawithsomeNSCLCCellsareapprox.2X’sthesizeofnormallymphocytesSCLC,pathologySCLC,pathologySCLC,clinicalpresentationTypicallyarisecentrallyMostcommonpresentationisalargehil

4、armasswithbulkymediastinalLANCommonsymptomscough,SOB,wtlossApprox.70%withovertmetsatpresentationCommonlyspreadtoliver,adrenals,boneandbrainCanpresentwithparaneoplasticsyndomeSCLC,tumormarkers3maingroups:Neural,Epithelial,NeuroendocrineEpithelial:virtuallyallSCLCsareimmunoreactivefor

5、KeratinandEpithelialMembraneAntigen1ormoremarkersofNeural/Neuroendocrinedifferentiationfoundinapprox.75%ofSCLCsSCLC,tumormarkersLeadstoexpressionofdopadecarboxylase,calcitonin,neuron-specificenolase,chromograninA,CD-56(aneuralcelladhesionmolecule)gastrinreleasingpeptideandinsulin-li

6、kegrowthhormoneOccasionallypatientsproduceantibodiesthatcross-reactwithboththeSCLCcellsandtheCNScerebellardegenerationsyndromesSCLCcellscanproduceanumberofpolypeptidehormonesincludingACTHandVasopressinNeurologicParaneoplasticSyndromesLungcancer,ParaneoplasticSyndromesSCLC,geneticsD

7、evelopmentoflungcancersoccurthroughstimulationofproliferationandmutagenesis,occurringoverYEARSandresultingfromexposuretotobaccoandothercarcinogensSCLC,geneticsThemostcommongeneticsofSCLCare:P53mutationispresentin75-90%Lossofheterozygosityofc-somes9pand10qinthemajorityDeletionof3pin

8、activationofasmanya