血浆中表皮生长因子受体（EGFR）突变状态的检测具有可重复性，并且能够动态预测表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）的疗效。

The detection of EGFR mutation status in plasma is reproducible and can dynamically predict the efficacy of EGFR-TKI.

作者信息

Huang Zhen, Wang Zhijie, Bai Hua, Wu Meina, An Tongtong, Zhao Jun, Yang Lu, Duan Jianchun, Zhuo Minglei, Wang Yuyan, Wang Shuhang, Wang Jie

机构信息

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Medical Oncology, Peking University School of Oncology, Beijing Cancer Hospital & Institute, Beijing, China.

出版信息

Thorac Cancer. 2012 Nov;3(4):334-340. doi: 10.1111/j.1759-7714.2012.00133.x.

DOI:10.1111/j.1759-7714.2012.00133.x

PMID:28920271

Abstract

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.

摘要

背景

表皮生长因子受体（EGFR）突变在血清和血浆DNA中作为肿瘤组织替代物的有效性已得到全面研究。然而，外周血和肿瘤组织样本在EGFR突变检测中的一致性仍然存在差异。在表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）治疗前是否需要进行EGFR突变分析的实时样本这一问题仍未得到解答。

方法

本研究包括两个队列：（i）822例非小细胞肺癌（NSCLC）患者，在初次诊断时采集了原发性肿瘤组织和匹配的血浆样本；（ii）207例晚期NSCLC患者，在EGFR-TKI治疗前立即采集了血浆样本，其中157例有匹配的肿瘤组织。变性高效液相色谱（DHPLC）测定EGFR突变状态。

结果

在总共822例有匹配样本的患者中，组织样本和血浆样本中的EGFR突变率分别为36.3%和32.1%。两种样本之间EGFR突变的一致性为77.0%（631/822），血浆DNA中EGFR突变的准确率为63.5%（188/296）。在207例晚期NSCLC患者中，在EGFR-TKI治疗前立即采集了血浆样本，无论EGFR-TKI的治疗线数如何，EGFR突变患者在EGFR-TKI治疗后的客观缓解率（ORR）显著高于EGFR野生型患者（51.4%对22.6%，P<0.001）。在接受两线或更多线EGFR-TKI治疗的患者中，血浆样本而非组织中的EGFR突变状态是EGFR-TKI治疗后无进展生存期（PFS）的预测指标（突变型对野生型：10.1个月对3.7个月，P=0.038）。