TheJournalofInternationalMedicalResearch2009;37:927–938927ComparativeAnalysisofProteinExpressioninDifferentiatedThyroidTumours:aMulticentreStudyH-SLIANG1,3,Y-HZHONG1,Z-JLUO4,YHUANG5,H-DLIN6,MLUO7,S-ZHAN2,H-XSU1,S-BZHOU1ANDK-QXIE31DepartmentofEndocrinology,and2DepartmentofPathology,NinthAffiliatedHospital,GuangxiMedicalUniversity,Beihai,China;3DepartmentofEndocrinology,NanfangHospital,SouthernMedicalUniversity,Guangzhou,China;4DepartmentofEndocrinology,FirstAffiliatedHospital,GuangxiMedicalUniversity,Nanning,China;5DepartmentofHepatobiliaryandEndocrineSurgery,GuangxiPeople’sHospital,Nanning,China;6DepartmentofHepatobiliaryandEndocrineSurgery,GuangxiPingnanPeople’sHospital,Pingnan,China;7ShanghaiEndocrineandMetabolismResearchInstitute,Shanghai,ChinaThisstudycomparedclinicalfeaturesandproteinexpressionprofilesindifferentiatedthyroidtumourstoidentifyproteinmarkerswiththepotentialforindicatingmalignancystatus.Tissuemicroarrayswereconstructedusing119thyroidtumoursamples(45papillarycarcinomas,26follicularcarcinomas,48adenomas).Generally,therewasoverexpressionofproliferatingcellnuclearantigen(PCNA),p53,matrixmetalloproteinase(MMP)-7,HectorBattiforamesothelial-1(HBME-1),MMP-2,pituitarytumour-transforminggene(PTTG)andhumantelomerasereversetranscriptase(hTERT)inmalignantthyroidcarcinomas,andoverexpressionoffragilehistidinetriad(FHIT),p16andE-cadherininthyroidadenomas.MultiplefactorbinarylogisticregressionanalysisindicatedthatMMP-2,HBME-1,p16andFHITwereindependentlyrelatedtodifferentiatedthyroidtumours.Receiver–operatingcharacteristicsforthesefourfactorsshowedHBME-1asbestfordiagnosticaccuracy.SensitivityandspecificitywereenhancedusinganHBME-1andp16cluster.HBME-1expressionwasnotsignificantlydifferentforpapillaryandfollicularcarcinomas,whereasp16expressionwassignificantlyspecific.KEYWORDS:DIFFERENTIATEDTHYROIDTUMOURS;CARCINOMAS;ADENOMAS;DIAGNOSIS;SENSITIVITY;SPECIFICITY;IMMUNOHISTOCHEMISTRY;PROTEINEXPRESSIONIntroductionThyroidneoplasmsareverycommonendocrinetumours,howeveritissometimesdifficulttodistinguishbetweenbenignandmalignantneoplasmsbecausesimilarclinicalmanifestationsarefrequentlyencounteredduringintumescencecolourimaginginvestigations.Numerousresearchershavedemonstratedthevalueofhistopathologicalcriteriainpredictingwhetherthyroidneoplasmsarebenignormalignant,howeverdifficultiesremainindistinguishingbetweensomemalignantandbenigndifferentiatedthyroidtumours.1928H-SLiang,Y-HZhong,Z-JLuoetal.ProteinexpressionindifferentiatedthyroidtumoursThediagnosticvalueofanumberofimmunohistochemicalstainshasbeenstudiedinthyroidneoplasms,forexamplefragilehistidinetriad(FHIT),metalloproteinase(MMP)-2,MMP-7,p53,p16,pituitarytumour-transforminggene(PTTG)andproliferatingcellnuclearantigen(PCNA).Thesestainshavebeenvalidatedassimple,reliableandrepeatablemarkersforuseinthediagnosisofmalignantandbenignthyroidtumoursinhumans.2–5Somehavealsobeenshowntobeprognosticallyrelevantinothertypesoftumour.2However,noconsistentcorrelationsofdiagnosticvaluehavebeenidentifiedbetweenthesecancer/anti-cancerproteinsandtumourhistopathology.3,5Inaddition,multi-proteinprofilingusingimmunohistochemicalanalysisoftissuehasbeenshowntobeanefficient,reproducibleandvalidmethodtostudycanceroranti-cancerproteinsinendocrineneoplasms.6–8Themainobjectiveofthisstudywastouseimmunohistochemicalanalysesinthyroidcarcinomaandthyroidad...
