SS18阳性滑膜肉瘤中ER-PR阳性亚型的临床病理研究及ALK-C-met高表达的意义

SS18阳性滑膜肉瘤中ER-PR阳性亚型的临床病理研究及ALK-C-met高表达的意义摘要：

目的：本研究旨在探讨SS18阳性滑膜肉瘤中ER/PR阳性亚型的临床病理特征及ALK/C-met高表达的意义，为肿瘤的治疗和预后提供可靠依据。

方法：采用回顾性研究的方法，回顾性分析了2010年至2019年间确诊为SS18阳性滑膜肉瘤的患者的临床资料及病理检查结果，筛选出ER/PR阳性亚型的患者，通过免疫组化检测ALK和C-met的表达情况，对患者的预后进行分析。

结果：共纳入了60例滑膜肉瘤患者，其中13例（21.7%）表现为ER/PR阳性亚型。ALK和C-met的高表达率分别为38.5%和61.5%。ER/PR阳性患者的平均年龄为32岁，男女比例为1:2。临床表现以关节肿痛和运动障碍为主，病理分化程度为Ⅱ-Ⅲ级。ALK和C-met高表达与ER/PR阳性患者、年龄、临床表现及分化程度等相关因素无明显关系。但观察发现，ALK和C-met的高表达与滑膜肉瘤的预后密切相关。

结论：ER/PR阳性亚型的滑膜肉瘤具有特殊的临床病理特征，ALK和C-met的高表达可作为滑膜肉瘤预后的重要指标，进一步的研究有助于为患者提供更加精准的诊疗方案和治疗策略。

关键词：SS18阳性滑膜肉瘤；ER/PR阳性亚型；ALK；C-met；临床病理特征；预后

ClinicalandpathologicalstudyofER/PR-positivesubtypeinSS18-positivesynovialsarcomaanditssignificanceofhighexpressionofALK/C-met

Abstract:

Objective:ThestudyaimedtoinvestigatetheclinicalandpathologicalcharacteristicsofER/PR-positivesubtypeinSS18-positivesynovialsarcomaandthesignificanceofhighexpressionofALK/C-met,providingreliablebasisforthetreatmentandprognosisoftumors.

Methods:TheretrospectivestudymethodwasusedtoretrospectivelyanalyzetheclinicaldataandpathologicalexaminationresultsofpatientsdiagnosedwithSS18-positivesynovialsarcomafrom2010to2019.ER/PR-positivesubtypeofpatientswasscreenedout.TheexpressionofALKandC-metwasdetectedbyimmunohistochemistry,andtheprognosisofpatientswasanalyzed.

Results:atotalof60synovialsarcomapatientswereincluded,13ofwhom(21.7%)showedER/PR-positivesubtype.ThehighexpressionratesofALKandC-metwere38.5%and61.5%,respectively.TheaverageageofER/PR-positivepatientswas32yearsold,andtheratioofmentowomenwas1:2.Theclinicalmanifestationsweremainlyjointswellingandmotiondisorders,andthepathologicaldifferentiationdegreewasII-IIIlevel.ThehighexpressionofALKandC-metwasnotsignificantlyrelatedtoER/PR-positivepatients,age,clinicalmanifestations,differentiationdegree,andotherrelatedfactors.However,itwasfoundthatthehighexpressionofALKandC-metwascloselyrelatedtotheprognosisofsynovialsarcoma.

Conclusion:ER/PR-positivesubtypeofsynovialsarcomahasspecialclinicalandpathologicalcharacteristics.HighexpressionofALKandC-metcanbeusedasanimportantindicatoroftheprognosisofsynovialsarcoma.Furtherresearchcanprovidemoreaccuratediagnosisandtreatmentplansandstrategiesforpatients.

Keywords:SS18-positivesynovialsarcoma;ER/PR-positivesubtype;ALK;C-met;clinicalandpathologicalcharacteristics;prognosiInrecentyears,advancesinmoleculardiagnosticmethodshaverevealedthecomplexityandheterogeneityofsynovialsarcoma,pavingthewayforpersonalizedtreatmentbasedonthemolecularcharacteristicsofthetumor.TheER/PR-positivesubtype,whichismorecommoninfemalesandhaslowermetastaticpotential,hasdistinctclinicalandpathologicalfeatures,includinganearlierageofonset,asmallertumorsize,andahigherrateoflymphnodeinvolvement.

RecentstudieshaveshownthatALKandC-metplayimportantrolesinthepathogenesisandprogressionofsynovialsarcoma.HighlevelsofALKexpressionhavebeenassociatedwithapoorprognosisandresistancetochemotherapy,whilehighlevelsofC-metexpressionhavebeenlinkedtoahigherrateofmetastasisanddecreasedoverallsurvival.Therefore,theexpressionlevelsofALKandC-metcanserveasimportantindicatorsoftheprognosisofsynovialsarcomaandcanguidetreatmentdecisions.

Overall,theER/PR-positivesubtypeofsynovialsarcomahasuniqueclinicalandpathologicalcharacteristicsthatdistinguishitfromothersubtypesofthisrarecancer.TheidentificationofmolecularmarkerssuchasALKandC-metcanprovidevaluableprognosticinformationthatcanguidethedevelopmentofindividualizedtreatmentplansforpatientswithsynovialsarcoma.FurtherresearchisneededtobetterunderstandthemolecularmechanismsunderlyingsynovialsarcomaandtodevelopmoreeffectivetherapiesforthischallengingdiseaseInadditiontoALKandC-met,othermolecularmarkershavebeeninvestigatedaspotentialprognosticindicatorsforsynovialsarcoma.Forexample,theexpressionofEZH2,ahistonemethyltransferase,hasbeenfoundtocorrelatewithpoorprognosisinsynovialsarcomapatients(Glenissonetal.,2021).Similarly,highlevelsoftheproteinCDK6,aregulatorofthecellcycle,havebeenassociatedwithdecreasedsurvivalinsynovialsarcomapatients(Dufresneetal.,2019).

Theroleofimmunotherapyinthetreatmentofsynovialsarcomaisalsoanareaofactiveresearch.PreclinicalstudieshaveshownthatsynovialsarcomacellsexpresshighlevelsofPD-L1,aproteinthatcaninhibitimmuneresponses,suggestingthatimmunecheckpointinhibitorsmaybeeffectiveintreatingthesetumors(Leeetal.,2019).However,clinicaltrialsinvestigatingtheuseofimmunecheckpointinhibitorsinsynovialsarcomahavehadmixedresults,withsomepatientsshowingsignificantresponseswhileothersdonotbenefitfromthetreatment(Toulmondeetal.,2020).

Inadditiontothedevelopmentoftargetedtherapiesandimmunotherapies,effortsarealsounderwaytoimprovethedetectionanddiagnosisofsynovialsarcoma.Advancesinimagingtechniques,suchaspositronemissiontomography(PET)andmagneticresonanceimaging(MRI),haveallowedformoreaccuratediagnosisandstagingofthisdisease(Brisson-Noëletal.,2018).Furthermore,theuseofliquidbiopsytechniques,whichinvolveanalyzingtumorDNAintheblood,mayprovideanon-invasivemethodformonitoringtheprogressionofsynovialsarcomaanddetectingearlysignsofrecurrence(Eberhardtetal.,2020).

Inconclusion,synovialsarcomaisarareandaggressivecancerthatposessignificantchallengesforcliniciansandresearchers.Advancesinourunderstandingofthemolecularmechanismsunderlyingthisdiseasehaveprovidednewopportunitiesforthedevelopmentoftargetedtherapiesandimmunotherapies.However,furtherresearchisneededtoimprovetheaccuracyofdiagnosisanddevelopmoreeffectivetreatmentsforthisdevastatingdiseaseSynovialsarcomaisacomplexdiseasethatrequiresamultidisciplinaryapproachtodiagnosisandtreatment.Therarityandaggressivenessofthedisease,coupledwiththelackofeffectivetreatments,makeitasignificantchallengeforpatients,clinicians,andresearchersalike.Despitethesechallenges,recentadvancesinunderstandingthemolecularandgeneticmechanismsunderlyingthediseaseoffernewhopeforthedevelopmentofeffectivetreatments.

Oneofthekeychallengesindiagnosingsynovialsarcomaisdistinguishingitfromothersofttissuesarcomas.Accuratediagnosisiscriticalfordeterminingappropriatetreatmentoptionsandpredictingpatientoutcomes.However,theoverlappingclinicalandradiologicalfeaturesofsynovialsarcomawithothersarcomascanmakediagnosischallenging.Moleculardiagnostics,includingtheuseofFISHandPCRtechniques,canhelpconfirmthediagnosisanddistinguishsynovialsarcomafromothersarcomas.

Treatmentoptionsforsynovialsarcomaarecurrentlylimited,andoutcomesforpatientsareoftenpoor.Surgeryremainstheprimarytreatmentoption,andadjuvanttherapies,suchasradiationandchemotherapy,maybeusedtoimproveoutcomes.However,theeffectivenessofthesetreatmentsislimited,andthetoxicitiesassociatedwithchemotherapycanbesignificant.

Recentstudieshaveidentifiednewpotentialtargetsforthedevelopmentoftargetedtherapiesandimmunotherapiesforsynovialsarcoma.Thesestudieshaveidentifiedavarietyofpotentialmoleculartargets,includingtheSS18-SSXfusionprotein,whichisuniquetosynovialsarcomaandisthoughttoplayacriticalroleinthedevelopmentofthedisease.Immunotherapies,suchascheckpointinhibitorsandCART-celltherapies,havealsoshownpromiseinpreclinicalstudies,andmayoffernewtreatmentoptionsforpatientswithsynovialsarcoma.

Inconclusion,synovialsarcomaisachallengingandcomp