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1、HeterogeneityofEpidermalGrowthFactorReceptorStatus andMutationsofKRAS/PIK3CAinCirculatingTumor CellsofPatientswithColorectalCancerClinicalChemistryNovember7，2012Studyintroduction美国国家癌症综合治疗联盟（NCCN）《结直肠癌临床实践指南》(2011)明确指出：(1)所有转移性结直肠癌患者都应检测KRAS基因状态；(2)只有KRAS野生型患者才建议接
2、受EGFR抑制剂（如爱必妥和帕尼单抗）治疗。NCCN《非小细胞肺癌临床实践指南》(2011)明确指出：当KRAS基因发生突变时，不建议使用EGFR-TKIs靶向治疗药物。卫生部颁布的《结直肠癌诊疗规范（2010年版）》也明确指出：确定为复发或转移性结直肠癌时，检测肿瘤组织KRAS基因状态，以确定合适的治疗方案。1. Amado R G，Wolf M，Peeters M，Van Cutsem E et al. Journal of Clinical Oncology. April 2008.2. Van Cutsem et al
3、. ASCO Annual Meeting 2008: abstract 2.3. Bokemeyer et al. ASCO Annual Meeting 2008: abstract 4000.4. Lièvre et al. J Clin Oncol 2008;26:374-9.5.美国FDA相关网站：http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm172905.htmEGFR是一种跨膜酪氨酸激酶受体，与配体结合后可引起下游信号传导通路的活化，如：KRASBRAF(4
4、%–12%)RAS-RAF-MEK-Erk/MAPKPIK3CA(14%–20%)P13K-AKT-PKC-IKK在许多实体瘤中EGFR均有不同程度的表达，表达率最高为头颈部肿瘤，达95%—100%。CRC次之，为72%—89%，胃癌表达率为41%—64%，并且EGFR表达率高的肿瘤恶性度高，侵袭力强，预后差。而且在同一患者中不同的CTCs中，EGFR的表达也存在着异质性。[1]GoldsteinNS,ArminM.Epidermalgrowthfactorreceptorimmunohistochemicalreactivi
5、tyinpatientswithAmericanJointCommitteeonCancerStageIVcolonadenocarcinoma:Implicationsforastandardizedscoring system[J].Cancer,2001,92(5):1331-1346.[2]BergstromJD,WestermarkB,HeldinNE.Epidermalgrowthfactorre-ceptorsignalingactivatesmetinhumananaplasticthyroidcarcinom
6、acells[J].ExperimentalCellResearch,2000,259(1):292-299. [3]DenningMF,DlugoszAA,ChengC,etal.Cross-talkbetweenepidermalgrowthfactorreceptorandproteinkinaseCduringcalciumnduceddifferentiationofkeratinoytes[J].ExperimentalDermatology,2000,9(3):192-199.Patients4Celllines
7、,cultureconditions,andfluorescenceinSituhybridizationanalysis(MCF,MDA-MB-468,BT-20,MDA-MB-468A)EnumerationofCTCsbyCS(FITC-thefourthchanneloftheCS)SamplepreparationformolecularanalysisafterCellSearchdetectionIsolationofCTCsbymicromanipulationWhole-GenomeAmplification
8、ofDNAfromsingletumorcellswiththeGenomePlexkitWGAofDNAfromsingletumorcellswiththeGenomiPhikitIdentificationofEGFRgeneamplificationsbyPCRonW
