SS18陽性滑膜肉瘤中ER-PR陽性亞型的臨床病理研究及ALK-C-met高表達(dá)的意義

SS18陽性滑膜肉瘤中ER-PR陽性亞型的臨床病理研究及ALK-C-met高表達(dá)的意義摘要：

目的：本研究旨在探討SS18陽性滑膜肉瘤中ER/PR陽性亞型的臨床病理特征及ALK/C-met高表達(dá)的意義，為腫瘤的治療和預(yù)后提供可靠依據(jù)。

方法：采用回顧性研究的方法，回顧性分析了2010年至2019年間確診為SS18陽性滑膜肉瘤的患者的臨床資料及病理檢查結(jié)果，篩選出ER/PR陽性亞型的患者，通過免疫組化檢測ALK和C-met的表達(dá)情況，對患者的預(yù)后進(jìn)行分析。

結(jié)果：共納入了60例滑膜肉瘤患者，其中13例（21.7%）表現(xiàn)為ER/PR陽性亞型。ALK和C-met的高表達(dá)率分別為38.5%和61.5%。ER/PR陽性患者的平均年齡為32歲，男女比例為1:2。臨床表現(xiàn)以關(guān)節(jié)腫痛和運動障礙為主，病理分化程度為Ⅱ-Ⅲ級。ALK和C-met高表達(dá)與ER/PR陽性患者、年齡、臨床表現(xiàn)及分化程度等相關(guān)因素?zé)o明顯關(guān)系。但觀察發(fā)現(xiàn)，ALK和C-met的高表達(dá)與滑膜肉瘤的預(yù)后密切相關(guān)。

結(jié)論：ER/PR陽性亞型的滑膜肉瘤具有特殊的臨床病理特征，ALK和C-met的高表達(dá)可作為滑膜肉瘤預(yù)后的重要指標(biāo)，進(jìn)一步的研究有助于為患者提供更加精準(zhǔn)的診療方案和治療策略。

關(guān)鍵詞：SS18陽性滑膜肉瘤；ER/PR陽性亞型；ALK；C-met；臨床病理特征；預(yù)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-No?letal.,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