The detection of EGFR mutation status in plasma is reproducible and can dynamically predict the efficacy of EGFR-TKI
The detection of EGFR mutation status in plasma is reproducible and can dynamically predict the efficacy of EGFR-TKI
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DOI：
10.1111/j.1759-7714.2012.00133.x
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发表时间：
2012-11-01
期刊：
影响因子：
2.9
通讯作者：
Wang, Jie
中科院分区：
文献类型：
--
作者：
Huang, Zhen;Wang, Zhijie;Wang, Jie
背景：血清和血浆DNA中表皮生长因子受体(EGFR)突变作为肿瘤组织替代物的有效性已被广泛研究。然而，外周血和肿瘤组织样本在检测EGFR突变方面的一致性仍然存在差异。关于在表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKI)治疗前是否需要实时样本进行EGFR突变分析的问题仍然没有答案。方法：这项研究包括两个队列：(I)822例初诊时有原发肿瘤组织和匹配的血浆样本的非小细胞肺癌(NSCLC)患者；(Ii)207例在EGFR-TKI治疗前立即采集血浆样本的晚期NSCLC患者，其中157例有匹配的肿瘤组织。结果：在822例配对标本中，组织标本和血浆标本中EGFR突变率分别为36.3%和32.1%。两种标本EGFR突变的符合率为77.0%(631/822)，与血浆DNA中EGFR突变的符合率为63.5%(188/296)。在207例在EGFR-TKI治疗前立即采集血浆样本的晚期非小细胞肺癌患者中，EGFR-TKI治疗后的客观有效率在EGFR-TKI治疗后显著高于EGFR野生型患者(51.4%vs.22.6%，P<；0.001)，与EGFR-TKI的治疗路线无关。在接受两条或两条以上EGFR-TKI治疗的患者中，血浆样本中的EGFR突变状态是EGFR-TKI治疗后无进展生存(PFS)的预测因素(突变型和野生型分别为10.1个月和3.7月，P=0.038)。结论：利用血浆样本进行的EGFR突变检测是有效和可重复性的。为了预测EGFR-TKI的结果，获得EGFR突变检测的实时样本是至关重要的。
Background: The validity of epidermal growth factor receptor (EGFR) mutation in serum and plasma DNA as a surrogate of tumor tissue has been comprehensively explored. However, the concordance between peripheral blood and tumor tissue samples in EGFR mutation detection remains variable. The question as to whether real-time samples for EGFR mutation analysis are required before epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy remains unanswered.Methods: This study included two cohorts:(i) 822 non-small cell lung cancer (NSCLC) patients with primary tumor tissue and matched plasma samples at initial diagnosis; and (ii) 207 patients with advanced NSCLC who had plasma samples taken immediately before EGFR-TKI therapy, in which 157 cases had matched tumor tissues. Denaturing High-Performance Liquid Chromatography (DHPLC) determined EGFR mutation status.Results: Among a total of 822 patients with matched samples, the EGFR mutation rates were 36.3% and 32.1% in tissue and plasma samples, respectively. Concordance of EGFR mutation between two kinds of samples was 77.0% (631/822),with 63.5% (188/296) of accuracy of EGFR mutation in plasma DNA. In 207 advanced NSCLC patients who had plasma samples taken immediately before EGFR-TKI therapy, the objective response rate (ORR) after EGFR-TKI therapy was significantly higher in EGFR mutant patients than those in EGFR wild-type patients (51.4% vs. 22.6%, P < 0.001), regardless of the treatment lines of EGFR-TKI. In patients with two or more lines of EGFR-TKI therapy, EGFR mutation status in plasma samples, but not in tissues, was a predictor for progression-free survival (PFS) after EGFR-TKI therapy (mutant vs. wild-type: 10.1 months vs. 3.7 months, P = 0.038).Conclusions: An EGFR mutation test using plasma DNA samples was validated and reproducible. Obtaining real-time samples for EGFR mutation detection is critical in order to predict the outcomes of EGFR-TKI.