| ObjectiveEGFR mutation status is the key to the benefit from EGFR-TKI in NSCLC patients,while,some patients can't get enough tissue samples for mutation detection at time of diagnosis.“Liquid biopsy”,an important sample of EGFR gene mutation detection,has become a hot spot in clinical attention in recent years.In this assay,by detection the EGFR mutation status of tissue and plasma samples,the consistency of the two methods is compared.Additionally,the correlation between EGFR mutation status and patient's clinical baseline characteristics as well as EGFR-TKI efficacy were also analyzed.Methods1.One hundred and twenty-one patients with NSCLC in Cancer center,Daping Hospital,Third Military Medical University from August 2011 to August 2014 were enrolled in this study and the clinical data of patients were collected.All patients were diagnosed as NSCLC by pathological examination and there were enough tissue samples to detect the mutation status.EGFR mutation status in tumor tissue were detected by amplification refractory mutation system(ARMS),while in matched plasma samples were detected by the restriction endonuclease digestion combine with denaturing high performance liquid chromatography method(REDE-DHPLC).The relationship of EGFR mutation status with patients' clinical characteristics at baseline was analyzed and the consistency between the two methods was compared.2.Fifty-nine patients of the 121 matched patients were treated with EGFR-TKI and the prognosis of patients were followed up.The correlation between EGFR mutation status and the efficacy of EGFR-TKI was analyzed.Results1.EGFR mutation rate in tumor tissue was 36.4%(44/121),including 18.2 %(22/121)deletion mutations in exon 19 and 18.2 %(22/121)L858R substitute mutations in exon 21.Thirty-four point seven percent(42/121)matched plasma samples exhibited mutations,which included 19.0 %(23/121)deletion mutations in exon 19 and 15.7 %(19/121)L858R substitute mutations in exon 21.Taking the tissue test results as the "gold standard",the sensitivity,specificity,positive predictive value,and negative predictive value of plasma EGFR mutations were 77.3%,89.6%,81.0%,and 87.3%,respectively.Two kinds of detection methods had better consistency(Kappa=0.675,P<0.001).2.The correlation analysis between tissue and plasma EGFR mutation status and the clinical baseline characteristics of patients showed that the mutation rate of female,adenocarcinoma,non-smoking and CEA level increased was significantly higher than that of male,other tissue types,smoking and normal CEA levels(Gender: in tissue 70.7% vs 18.8%,P < 0.001;in plasma 63.4% vs 20.0%,P < 0.001.Histological types: in tissue 43.3% vs 8.3%,P =0.001;in plasma 41.2% vs 8.3%,P = 0.002.Smoking histor: in tissue 52.2% vs 15.4%,P < 0.001;in plasma 46.4% vs 19.2%,P = 0.002.CEA level: in tissue 44.6% vs 27.3%,P <0.049;in plasma 46.2% vs 21.8%,P = 0.005).Multivariate Logistic analysis showed that gender,histological types were the independent predictors of EGFR mutations both in tissue and plasma for patients with NSCLC.CEA level was also an independent predictor of EGFR mutations in plasma.3.Fifty-nine patients were treated with EGFR-TKI.A significantly higher objective response rate(ORR),median progression free survival(mPFS)and median overall survival(mOS)were observed in patients harboring EGFR mutation than those without EGFR mutation(ORR: in tissue 69.4% vs 13.0%,P <0.001;in plasma 64.5% vs 28.6%,P = 0.006.m PFS: in tissue 10.4 months vs 4.1 months,P <0.001;in plasma 10.5 months vs 5.2 months,P = 0.001.mOS: in tissue 25.7months vs 8.3months,P =0.005;in plasma 25.7months vs 13.5 months,,P = 0.038).ConclusionThe detection of EGFR mutation in plasma is in well agreement with the matched tissue.Gender and histological types are independent predictors of EGFR mutations both in plasma and tumor tissue for patients with NSCLC.EGFR-TKI can significantly improve the clinical efficacy of EGFR mutant patients.Tissue and plasma EGFR mutation status all can be used to guide clinical EGFR-TKI treatment. |
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