2013Biological and molecular aspects of lymph node metastasis in gastro-intestinal cancer
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·论著·食管鳞癌中CD137L表达及其与肿瘤转移和微血管密度的相关性
安秀英 胡锋超 张 晶 王 萍 窦 艳 张华英 【摘要】 目的 探讨食管鳞癌中CD137配体(CD137L)表达及其与肿瘤转移和微血管密度(MVD)的相关性。方法 收集2017年1月至2018年6月在河北省民政总医院外科住院手术的80例患者的食管鳞癌组织和癌旁正常组织(距肿瘤边缘>5cm),采用定量PCR(qPCR)法检测组织中犆犇137犔mRNA的相对表达量,采用免疫组织化学法检测CD137L蛋白的表达,分析CD137L蛋白阳性表达与肿瘤浸润深度、组织学分级、淋巴结转移的关系。用CD105标记MVD,采用免疫组织化学法检测CD105的表达并计算MVD值。比较CD137L蛋白阳性和阴性表达的食管鳞癌患者的MVD差异,分析犆犇137犔mRNA与MVD的相关性。结果 食管鳞癌组织中犆犇137犔mRNA
的相对表
达量显著低于癌旁正常组织,差异有统计学意义(犘<0.05)。免疫组织化学结果显示,食管鳞癌组织中CD137L蛋白主要表达在细胞膜,少量表达在细胞质,CD137L蛋白表达阳性率显著低于癌旁正常组织,差异有统计学意义(犘<0.05)。肿瘤浸润深度越深,CD137L蛋白阳性表达率越低,有淋巴结转移的患者的CD137L蛋白阳性表达率低于无淋巴结转移的患者,差异均有统计学意义(犘均<0.05)。CD105蛋白主要表达于血管内皮细胞,食管鳞癌组织中MVD显著高于癌旁正常组织[(36.92±6.55)/mm2比(10.17±
2.12)/mm2],差异有统计学意义(狋=10.002,犘=0.000)。CD137L蛋白阳性表达患者的
MVD显著低于阴性表达患者[(31.94±6.13)/mm2比(41.77±6.08)/mm2],差异有统计学意义(犘<0.05)。犆犇137犔mRNA相对表达量与MVD呈显著负相关(狉=0.492,犘=0.000)。结论 食管鳞癌中CD137L表达呈低表达,CD137L
The distribution of position and size of lymph nodes detectedby CT in patients with cardiac carcinom aCU I Yan2hai,Z HA N G X i ao2peng3,TA N G L ei,S U N Yi ng2shi (Department of R adiolog y,Peking Universit y School of Oncology&B ei j ing Cancer Hos pital,B ei j ing100036,China)[Abstract] Objective To analyze the distributing characteristics and the range of size of lymph nodes(L N)detected by helical computed tomography(CT)in patients with cardiac carcinoma.Methods Helical CT was performed in65patients with cardiac carcinoma.Picture archiving and communication system(PACS)was used.The f requency of nodes in each sta2 tions and the size of each L N were retrospectively studied.Sensitivity and specificity were evaluated by means of receiver op2 erator characteristic curve(ROC).R esults ①The majority of L Ns detected by CT located at pericardia and lesser gastric curvature,followed by left gastric artery and the celiac trunk stations.The detection rate and percentage were No.1:89% and23%,No.2:66%and8%,No.3:92%and25%,No.7:54%and7%,No.9:44%and6%,respectively.The L Ns at lower mediastinum stations were fewer than that of abdominal stations.②Percentages of nodes smaller than10mm,8 mm,5mm in size were76.9%,60.3%,24.8%in node metastases group,respectively.③According to ROC analysis, when5mm,8mm,11mm size criterions were applied,the sensitivity and specificity were90.7%and21.9%,51.5%and 74%,13.1%and95.8%,respectively(Az=0.661).Conclusion ①The majority of lymph nodes in cardiac carcinoma de2 tected by CT locate at abdomen.②Most nodes of cardiac carcinoma with lymph node metastasis have small size,with<8 mm’s accounting for60.3%.③It is difficult to obtain both high sensitivity and specificity using size indictor to judge lymph node metastasis detected by CT.[K ey w ords] Cardiac neoplasms;L ymph node metastases;Tomography,X2ray computed贲门癌CT检出淋巴结分布的影像学特点崔燕海,张晓鹏3,唐 磊,孙应实(北京大学临床肿瘤学院暨北京肿瘤医院放射科,北京 100036)[摘 要] 目的 分析贲门癌CT检出淋巴结的部位及大小分布特点。
《中国癌症杂志》2020年第30卷第1期 CHINA ONCOLOGY 2020 Vol.30 No.149欢迎关注本刊公众号·论 著·基金项目:国家自然科学基金(81971687);上海市青年科技英才扬帆计划资助(19YF1409900)。
通信作者:童 彤 E-mail: t983352@术前预测结直肠癌淋巴结转移的临床-影像 组学列线图的建立和验证李梦蕾1,张 敬2,淡一波2,杨 光2,姚叶锋2,童 彤11.复旦大学附属肿瘤医院放射诊断科,复旦大学上海医学院肿瘤学系,上海 200032;2.华东师范大学上海市磁共振重点实验室,上海 200062[摘要] 背景与目的:术前准确预测淋巴结转移对于结直肠癌患者的肿瘤分期、治疗决策、预后及复发等至关重要。
建立和验证用于术前预测结直肠癌淋巴结转移的临床-影像组学组合模型。
方法:收集复旦大学附属肿瘤医院收治的767例经病理学检查确诊为结直肠癌的患者(实验组537例,验证组230例)。
然后纳入9个重要临床危险因素[年龄、性别、术前癌胚抗原(carcinoembryonic antigen ,CEA )水平、术前糖类抗原19-9(carbohydrate antigen 19-9,CA19-9)水平、病理学分级、组织学类型、肿瘤位置、肿瘤大小和M 分期]来构建临床模型;采用ANOV A 、Relief 和递归特征消除(recursive feature elimination ,RFE )进行特征选择(包括临床危险因素、原发病灶和周围淋巴结的影像组学特征),通过逻辑回归分析建立各自的分类模型,并通过one-standard-error 准则选择最优模型,然后组合最优模型下的临床危险因素、原发灶影像组学特征、周围淋巴结影像组学特征建立联合预测模型。
接着使用受试者工作特征(receiver operating characteristic ,ROC )曲线及曲线下面积(area under curve ,AUC )来量化预测准确率。
ted transformation[J].Mol Cell Biol,2012,32(19):3913-3924.[28]You YJ,Chen YP,Zheng XX,et al.Aberrant methylation of the PTPRO gene in peripheral blood as a potential biomarker in e-sophageal squamous cell carcinoma patients[J].Cancer Letters,2012,315:138-144.(编校:闫沛)胃癌肝转移治疗研究进展于先强1,郑志超2T reatment strategy of gastric cancer with liver metastasesYu Xianqiang1,Zheng Zhichao21Graduate School of Dalian Medical University,Liaoning Dalian116000,China;2The Stomach Surgery Department,Liaoning Cancer Hospital and Institute,Liaoning Shenyang110042,China.【Abstract】Liver metastasis is a late event in gastric cancer.It results in the failure of curative gastric cancer surgery.Now standard clinical treatment strategy is impending.The aim of GCLM treatment should not only improve the qualityof life,but prolong survival period.Properly selected indication is the key of successful treatment.Sole methods oftreatment is hard to get good effect,and therapeutic alliance is widely adopted in the clinic.Multidisciplinary treat-ments make it possible for GCLM patients of long survival period.【Key words】gastric cancer;liver metastasis;multidisciplinary treatmentModern Oncology2013,21(10):2373-2375【指示性摘要】胃癌肝转移(gastric cancer with liver metastases,GCLM)是胃癌进展到晚期发生的不良事件,亦是胃癌治疗失败的重要原因之一,难以达到根治目的,目前临床上始终无法给出规范的治疗策略。
REVIEWARTICLEBiologicalandmolecularaspectsoflymphnodemetastasisingastro-intestinalcancer
KoshiMimori•YoshiharuShinden•
HidetoshiEguchi•TomoyaSudo•KeishiSugimachi
Received:7June2013/Publishedonline:5July2013ÓJapanSocietyofClinicalOncology2013
AbstractRecently,theexistenceoflymphnodemicro-metastasis,includingisolatedtumorcells,hasbeenthefocusofthedevelopmentofmoleculardiagnostictoolsforlymphnodemetastasisinvariousmalignantneoplasms,includingthoseoftheGItract.Inthisreview,wesum-marizerecentmolecularbiologicalstudiesthatmightprovidetworeasonstoexplainthesurvivalofsingleiso-latedcancercellsinlymphnodes.Oneisthespecificcharacteristicsofcancercells,whichcanexistunderseverecircumstances,alongwithrecenttechnologicalinnovationstoobtainexpressionprofilesandsequencingfromasinglecell.Theotherismicroenvironmentalfactorsthatsupporttheformationofmicrometastasiseveninsmallnumbersofcancercells.Theexpressionprofileofwholetranscriptomesequencing,genomicsequencingandepigeneticsequenc-ingofasinglecancercellwithtumorigenicpropertiesinlymphnodemetastasesshouldbedisclosedinthenearfuture.
KeywordsCancerstemcellÁIsolatedtumorcellÁMicroenvironmentÁChemokine
IntroductionLymphnodemetastasisisconsideredtoresultfromtheoncogenicactivityofcancercellsmediatedthroughthelymphogenousmetastaticprocess,anddeterminestheprognosisofpatientswithcancer.Therefore,accurate
comprehensionofitsmolecularandbiologicalaspectsisrequired.Oneaspectisthatcancercellshaveanabilitytoformmicrometastasesinregionallymphnodes.Manyepithelialcellsdieviaapoptoticandnon-apoptoticpath-ways,suchasautophagy[1]afterevacuationfromprimarysitesintothecirculatorysystem.However,malignantcellscansurviveandformmetastases.Whenconsideringthehostfactors,wesuggesttwopossiblemechanismsinthemicroenvironmentthatmaypromotetheformationoflymphnodemetastasis;oneisthatcancercellsdonotdoanything,butarecapturedmechanicallybythelymphnode.Inotherwords,cancercellsarepassivelyretrievedinregionallymphnodes.Itislikelythatthemicroenviron-mentinthelymphnodemightsupportthechangeofamicrometastasisintoalymphnodemetastasis.Second,severalstudieshaveindicatedthatlymphnodemetastasisbyactivecancercellsformstumornestsinlymphnodes.Inthiscase,isolatedtumorcellsinlymphnodesmusthavespecificpropertiestoformmicrometastasis.Inthisreview,wehavefocusedonthebiologicalandmolecularaspectsofmicrometastasisinlymphnodesingastrointestinaltractcancers.Micrometastasisisdefinedasamicroscopicdepositofmalignantcells,lessthan2mmindiameter,separatedfromtheprimarytumor.Thisdoesnotincludediscontinuousgrowthintheperitumoralregion,butitdoesincludethemicroenvironmentofregionallymphnodes.
ClinicalsignificanceofmicrometastasisinGItractmalignancies
Priortointroducingthebasicaspectsofmicrometastasisincancer,wemustfirstdemonstratetheclinicalsignifi-canceofmicrometastasis.Fukagawaetal.[2]concludedthatthepresenceofimmunohistochemically(IHC)detected
K.Mimori(&)ÁY.ShindenÁH.EguchiÁT.SudoÁK.SugimachiDepartmentofSurgery,KyushuUniversityBeppuHospital,4546Tsurumihara,Beppu874-0838,Japane-mail:kmimori@beppu.kyushu-u.ac.jp
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IntJClinOncol(2013)18:762–765DOI10.1007/s10147-013-0587-9micrometastasesintheregionallymphnodesdidnotaffectthesurvivalof107JapanesepatientswithpT2N0M0gastriccarcinomawhohadundergonegastrectomywithD2lymphnodedissection.ThepresenceofIHC-detectedlymphnodemicrometastasescorrelateswithworseprognosisforpatientswithhistologicnode-negativegastriccancer.Therefore,thereisnodefinitiveagreementaboutriskfac-torsortheclinicalsignificanceofmicrometastaticnodeinvolvementinpatientswithgastricadenocarcinoma[3].Similartogastricadenocarcinoma,theclinicalsignificanceofmicrometastasisingastro-intestinaltractlymphnodesiscontroversial,andthistopicwillbereviewedinanotherarticleinthisjournal.
Natureofasinglecancercelltoformamicrometastasisinalymphnode
Potentialfactorsregulatingdormancyinisolatedtumorcells(bonemarrow)
Asmentionedabove,micrometastaseswereoriginallydefinedassmalloccultmetastases(0.2cminthegreatestdimension).Sensitivetechniqueshavenowbeendevelopedthatallowthedetectionofsinglecancercellsamongmil-lionsofnormalcellsinthebloodandbonemarrow.Wikmanetal.[4]describedtheimportantroleofpotentialfactorscontrollingtumorcellsinbonemarrowasfollows:angiogenicfactors(HIF1alpha[increase][5],VEGF[increase]),immunologicalfactors(CD274[decrease][6],HLAclassIantigen[increase]),phenotypiccharacteristics(Ki67[decrease],CD44?/CD24-,CK19?/MUC1-[7]),
oncogenesandmetastasissuppressorgenes(MUC[increase],HER2[increase],nm23-H1[decrease],KISS1[decrease][8]),growthstimulatoryfactors(EGFR/uPARpathway[increase][9],ERKandp38pathway[increase][10])andmicroenvironmentepithelial-stromalcross-talk(CXCL12)[increase][11].Again,thosefactorslistedabovehavebeendiscussedpreviouslyinisolatedtumorcellsinbonemarrow;however,wespeculatedthattumorcellsinlymphnodesmustusesimilarprocessestoformmicrometastases.Viablecancercellsmustbeisolatedfrommicrometastaticsitesinlymphnodes,andthisdreamwillbecomerealitywiththedevelopmentofrecentandfuturetechnologicalinnovations.