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1、甲状腺髓样癌的分子分型及治疗解放军第一一七医院戚晓平概况Histologicsubtypesofthyroidcancer①Papillary:approximately80%ofallthyroidmalignancies;②FollicularandHürthle:approximately11%;③Medullary:lessthan5%-8%;④Anaplastic:lessthan2%.IntroductionMedullarythyroidcancer(MTC)①SporadicMTC:approximately75
2、%;>50%somaticRETmutations(p.M918T)-predictapoorprognosis②HereditaryMTC:approximately25%;98%GermlineRETmutations,MEN2A(~95%)andMEN2B(~5%)Arisesfromtheneuralcrest-derived,calcitonin-secreting,parafollicularCcellsofthethyroidglandIntroduction①SporadicMTC:asolitaryanduni
3、lateralorapalpablecervicallymphnode②HereditaryMTC:multicentricandbilateraltheuppertomiddlepartsofthethyroidlobesIntroductionInvolvementofcervicallymphnodesisanearlyandcommonmanifestationintheclinicalcourseofthedisease,with35%to50%ormore,another10%to15%mayhavedistantm
4、etastasesatthetimeofinitialpresentation;DistantmetastaticspreadofMTCfrequentlyinvolvesthemediastinalnodes,lung,liver(>90%),andbones.p.C611YMEN2AMolecularAberrations(overexpression)①RETmutations②VEGFR-2③MET④EGFR⑤FGFR⑥RAS(sMTC---56%KRAS+;12%HRAS)(MutationsinRASappearto
5、bemutuallyexclusiveofRETabnormalities)SomaticRETmutationsMolecularpathways①PI3K/Akt/mTOR②MAPK③JNK④RAS/ERKPlaycriticalrolesinregulatingcellproliferation,differentiation,motility,apoptosis,andsurvivalDiagnosisandMonitoring①FNA,USandCT,MRIorECT(Ct>500pg/mL);②DNAanalysis
6、fortheRETgermlinemutationATA-2015,ETA-2013,NCCN-2017Guidelinesrecommend③TheMTCspecimenispositivelystainedforCt,chromograninA,andCEAorCongoRed.DiagnosisandMonitoring④Serum-basedbiomarkers:calcitoninandCEA(>50%)Preoperative:ⅰCEA(↑),Ct(-)--poorlydifferentiatedtumors,Rar
7、e;ⅱCt>100pg/mL--predictive–MTC;ⅲCt>150pg/mL,CEA>30ng/L--regionalspread;ⅳCt>3000pg/mL,CEA>100ng/L--distantspread.PredictorsofMTCprogress,includingrecurrenceandsurvivalDiagnosisandMonitoring④Serum-basedbiomarkers:calcitoninandCEAPostoperative:ⅰCt(↑)--thefirstsignoftumo
8、rrecurrence;ⅱCt(-)andsCt(-)--10-yearsurvivalrates(SR)of100%;yearlyCtmeasurements;ⅲCtdoublingtimes(DT)>1yr(2yr)--5-and10-yrSRof98%an
