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机构地区:[1]福建医科大学附属第一医院胸外科,福建福州350005 [2]南京军区福州总医院,福建福州350008 [3]福建医科大学病理学系,福建福州350004
出 处:《肿瘤基础与临床》2013年第5期390-395,共6页journal of basic and clinical oncology
基 金:福建省卫生厅青年科研基金资助项目(编号:2009-1-10);福建医科大学苗圃基金资助项目(编号:2010-MP010)
摘 要:目的检测非小细胞肺癌(NSCLC)组织EGFR基因突变与扩增状况及下游信号传导蛋白磷酸化的表达,分析它们相互之间及与临床病理特征之间的关系。方法收集NSCLC患者标本64例,采用荧光定量PCR和基因测序法检测EGFR第19、21外显子突变,FISH法检测EGFR基因扩增,免疫组化EliVisionTMplus两步法检测P-AKT、P-ERK1/2和P-STAT3的阳性表达。结果 64例NSCLC组织标本有18例(28.1%)发生了EGFR突变,FISH阳性检出36例(56.3%),P-AKT、P-ERK1/2和P-STAT3的阳性率分别为64.1%(41/64)、25.0%(16/64)和40.6%(26/64)。女性、吸烟指数低的患者EGFR基因突变率显著高于男性、吸烟指数高的患者(P<0.05);腺癌,Ⅰ、Ⅱ期,吸烟指数低的患者P-AKT阳性率高于非腺癌,Ⅲ期,吸烟指数低的患者(P<0.05);P-STAT3阳性率在Ⅰ、Ⅱ期患者中显著高于Ⅲ期(P<0.05)。结论 EGFR突变及P-AKT阳性表达与临床TKI优势人群基本相符,提示两者是临床遴选TKI适宜人群的重要参考指标。Objective To detect the situations of EGFR mutation and amplification and the phosphorylation ex- pressions of downstream signaling pathway protein in patients with non-small cell lung cancer (NSCLC). To analyse their relationships with clinical and pathological features. Methods All the 64 cases of NSCLC surgery specimens were collected. EGFR mutations in exons 19 and 21 were detected by fluorescent quantitation PCR and gene se- quencing. EGFR gene amplifications were detected by FISH method. And the positive expressions of EGFR down- stream signaling protein P-AKT, P-ERK1/2 and P-STAT3 were detected by EliVisionTM plus two-step immunohis- tochemical staining. Results Of all the 64 cases of NSCLC specimens, the EGFR mutations was observed in the 18 cases (28. 1% ), FISH positive expression in the 36 cases (56. 3% ), the P-AKT positive rate was 64. 1% (41/64), the P-ERK1/2 positive rate was 25.0% (16/64), the P-STAT3 positive rate was 40.6% (26/64). The rate of EGFR mutation and in female and lower-index smokers were significantly higher than those in male and higher-index smokers ( P 〈 0.05 ). The positive rate of P-AKT in adenocareinoma, stage Ⅰ and Ⅱ , lower-index smokers were higher than those in nonadenocarcinoma, stage Ⅲ ,higher-index smokers( P 〈0.05 ). The positive ex- pression rate of P-STAT3 in cancer with stage Ⅰand Ⅱ was higher than that in cancer with stage m ( P 〈 0. 05 ).Conclusion EGFR mutations and positive expression of P-AKT were consistent with the clinical EGFR-TKI advan- tage, which prompted that the two were important indexs for clinical selection of EGFR-TKI appropriate population.
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