子宫内膜癌分型优质PPT.ppt
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20-5.,EmGD是指在良性子宫内膜和浆液性子宫内膜上皮内癌(EIC)之间的一种过渡性病变从组织学上来说,子宫内膜腺体异型增生时细胞的非典型性介于静止期子宫内膜和EIC之间EmGD病变过程中发现一些形态学上没有任何不典型性的内膜腺体或腺上皮在p53染色后出现强阳性的现象,ZhengW,etal.Endometrialglandulardysplasia:
anewlydefinedprecursorlesionofuterinepapillaryserouscarcinoma:
PartI:
molecularfeatures.IntJSurgPathol2004;
12:
319331.,BenignEndometrialGlands,EmGD,EIC,EIC,53染色指数常介于正常子宫内膜和浆液性上皮内癌之间,EmGDEIC,H&
E,p53,BenignEndometrium,53基因突变在p53印记腺体和子宫内膜浆液性的肿瘤病变中高度一致,REp53signaturesEmGDEIC/ESC,*,EmGD符合癌前病变的特征,子宫内膜浆液性癌可能的发生模式,P53signature,EmGD,SerousEIC,ESC,Progression,DNAdamageP53mutationEpigeneticchanges,DNAdamageP53mutation+expansion+proliferation,DNAdamageP53&
othermutations+expansion+proliferation+malignancy,p53IHC,H&
E,Theclinicalandpathologicfeaturesofuterineserouscarcinomaandhigh-gradeserousovariancarcinoma(HGSOC)arequitesimilar.HighfrequencyofTP53mutationsissharedacrossthesetumorsubtypes(uterineserous,91%;
ovarianserous,96%)verylowfrequencyofPTENmutations(uterineserouscarcinoma,2%;
HGSOC,1%)DifferencesincludeahigherfrequencyofFBXW7,PPP2R1A,andPIK3CAmutationsinuterineserouscomparedtoHGSOCs,输卵管来源?
38例单纯USC的双侧输卵管进行SEE-FIM(SectioningandExtensivelyExaminingtheFIMbria),并对非肿瘤性子宫内膜进行彻底病理学检查、P53免疫组化EIC(Endometrialintraepithelialcarcinoma)58%(22/38);
Endometrialp53fociwereidentifiedin3patients.29%(11/38)输卵管受累;
其中9输卵管壁受累或淋巴结转移,而无STICSTICwasidentifiedin3patients(8%).furthersupportingEICasaprecursorlesiontoUSC.STICwaspresentin8%,suggestingthatthefallopiantubemayinfactrepresenttheprimarylesioninaminorityofpatientswithUSC.Thisfindingmayaccountfortheearlymultifocaldiseasedistributionobservedinthesepatients.,现有子宫内膜癌分型存在的问题,I型子宫内膜癌中并非都与雌激素相关,临床实践中可见少部分I型子宫内膜癌患者没有任何内分泌代谢紊乱的表现,其肿瘤细胞分化差,周围内膜呈萎缩性表现,有学者认为应将这类子宫内膜癌归入II型;
而相反,II型子宫内膜癌中也有少部分继发于增生性子宫内膜之上,似乎与雌激素相关在子宫内膜癌的WHO分类7中还存在其他类型的子宫内膜癌,如混合型子宫内膜癌,移形细胞癌,小细胞癌及未分化癌,它们虽然罕见,但并不应排除在子宫内膜癌的分型之外,现有的子宫内膜癌分型是基于流行病学研究之上的临床病理分型,它揭示了子宫内膜癌最常见的两种临床表象子宫内膜细胞是如何癌变,又是如何赋予对雌激素的不同反应性的?
除了上述提及的两型子宫内膜癌以外,是否还有其他类型的子宫内膜癌存在?
对于非激素依赖的II型子宫内膜癌,是否还可以进一步划分为各种亚型,发现更为精确的分子特性?
I型子宫内膜癌是否应进一步分亚型?
精准医学-在充分考虑每个病人个体的基因,环境和生活方式等前提下量体裁衣地制定个性化精确治疗和预防方案全基因组DNA序列全外显子组DNA序列、表达谱小RNA表观遗传修饰蛋白质组代谢组检测癌症的精准治疗:
正确的时间,正确的药物针对正确的人进行正确的治疗,基于基因特征的子宫内膜癌分类,子宫内膜癌二元论分型,基因突变特征I型:
PTEN,FGFR2,ARID1A,CTNNB1,PIK3CA,PIK3R1和KRASII型:
TP53,PIK3CA,和PPP2R1A早期高危术后辅助治疗浆液性癌CT内膜样癌-RT部分患者1年内复发,基于基因特征的子宫内膜癌分类,TCGA(TheCancerGenomeAtalas)POLE,mostlyinvolvedincellularmetabolismMSI,decreasedMLH1mRNAexpressionCNlow,elevatedprogesteronereceptor(PGR)expressionCNhigh,exhibitedthegreatesttranscriptionalactivityexemplifiedbyincreasedcellcyclederegulation(CCNE1,PIK3CA,MYC,andCDKN2A)andTP53mutationincludedmostserousandserous-likeendometrioidtumors,Somaticcopynumberalterationsinendometrialcarcinomas94%(50/53)浆液性癌、62%(8/13)混合性癌为CN-H另有12%子宫内膜样癌为CN-H,包括24%G3、5%G1/2内膜样癌提示子宫内膜样癌存在与传统组织学分类和细胞分级完全不同的亚群,2名病理学专家对TCGA研究中所涉及的75例FIGOG3子宫内膜样腺癌进行形态学再评价:
55例一致,6例不一致,14例不肯定其中6例符合浆液性癌形态学特征,但仅有2例符合浆液性癌基因学特征,另4例为典型的子宫内膜样癌基因学特征CN-H组15例中,2例形态学及基因学均符合浆液性癌特征,而另外13例至少有1位病理学家判定为子宫内膜样癌CN-L组一致性最好(90%;
=0.9),(POLE:
62%,=0.55;
microsatelliteinstability-high:
78%,=0.74;
andCN-H:
53%,=0.48)Thisreviewconfirmsthatmosthigh-gradeendometrialcarcinomasdiagnosedbyTCGAasFIGOGrade3endometrioidcarcinomaareindeedendometrioidcarcinomasbymorphologyandgenotype,andthatthereproducibilityofhistologicdiagnosisbetweenpathologistsvariesbetweentheTCGA-integratedgenomicclusters,RNAsequencingmitotic,hormonal,andimmunoreactiveElevatedprogesteronereceptor(PGR)expressionwasnotedintheCNlowcluster,suggestingresponsivenesstohormonaltherapyhormonalTheCNhighcluster,whichincludedmostserousandserous-likeendometrioidtumors,exhibitedthegreatesttranscriptionalactivityexemplifiedbyincreasedcellcyclederegulation(e.g.CCNE1,PIK3CA,MYC,andCDKN2A)andTP53mutation.ThisisconsistentwithreportsthatelevatedCDKN2Acandistinguishserousfromendometrioidcarcinomas.Approximately85%ofcasesintheCNhighclustersharedmembershipwiththemitoticmRNAsubtype.,ultra-mutatedgroupwithunusuallyhighmutationrates(232106mutations/Mb)andauniquenucleotidechangespectrum;
ahypermutatedgroup(18106mutations/Mb)ofMSItumors,mostwithMLH1promotermethylation;
agroupwithlowermutationfrequency(2.9106mutations/Mb)andmostofthemicrosatellitestable(MSS)endometrioidcancers;
agroupthatconsistsprimarilyofserous-likecancerswithextensiveSCNA(copy-numbercluster4)andalowmutationrate,Exomesequenceanalysis-Basedonacombinationofsomaticnucleotidesubstitutions,MSI,andSCNA,Pathwayalterations,分子分型意义,更客观