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比较研究在肺腺癌患者的恶性胸腔积液、血浆和肿瘤组织中检测到的 EGFR 突变。

Comparative study of EGFR mutations detected in malignant pleural effusion, plasma and tumor tissue in patients with adenocarcinoma of the lung.

机构信息

Beijing Cancer Hospital, Medical Oncology Department, Haidian District, Beijing, China.

Department of Medical Oncology, No. 307 hospital of the Chinese People's Liberation Army, Beijing, China.

出版信息

Lung Cancer. 2019 Sep;135:116-122. doi: 10.1016/j.lungcan.2019.05.018. Epub 2019 May 16.

Abstract

OBJECTIVES

The utility of malignant pleural effusion (MPE) as a source for determining EGFR mutations to guide EGFR TKI therapy in advanced adenocarcinoma of the lung remains unclear. This study compared MPE, plasma and tumor tissues as sources of biological samples for EFGR mutational analysis of lung adenocarcinoma patients.

MATERIALS AND METHODS

Total 295 MPE samples were retrospectively collected from lung adenocarcinoma patients. Matched tissue and plasma samples were available for 92 patients, and 248 patients had plasma samples. EGFR exon-19-deletion and exon 21-L858R mutation were detected with Denaturing high performance liquid chromatography (DHPLC). The concordance of EGFR mutation status in MPE, tissue, and plasma were evaluated, and the value of EGFR mutations in MPE with respect to efficacy of EGFR-TKI was investigated.

RESULTS

The EGFR mutation rate in MPE samples was 39.3% (116/295). The concordance between MPEs and tissues was 87.1% (Kappa = 0.71); the sensitivity and specificity of EGFR mutation in MPEs according to tissues was 71.4% and 96.5%, respectively. And 219 patients received EGFR-TKI, and the objective response rate was similar for patients with EGFR mutation either in MPE, tissues or plasma (57.6% vs 56.0% vs 47.4%, p = 0.51). Similar results were found in progression free survival (8.9 months vs 9.0 months vs 7.7 months, p = 0.077 and overall survival (29.8 months vs 25.9 months vs 25.3 months, p = 0.33).

CONCLUSION

MPE is a reliable surrogate for tumor tissue for identifyingEGFR mutations. MPE could offer reference of EGFR mutation to EGFR-TKIs treatment decision for advanced lung adenocarcinoma patients even when tissue and plasma were available.

摘要

目的

恶性胸腔积液(MPE)作为一种来源,用于确定表皮生长因子受体(EGFR)突变,以指导晚期肺腺癌的 EGFR TKI 治疗,其作用仍不明确。本研究比较了 MPE、血浆和肿瘤组织作为肺腺癌患者 EGFR 突变分析生物样本来源的价值。

材料与方法

回顾性收集了 295 例肺腺癌患者的 MPE 样本。92 例患者有匹配的组织和血浆样本,248 例患者有血浆样本。采用变性高效液相色谱法(DHPLC)检测 EGFR 外显子 19 缺失和外显子 21-L858R 突变。评估 MPE、组织和血浆中 EGFR 突变状态的一致性,并研究 MPE 中的 EGFR 突变与 EGFR-TKI 疗效的关系。

结果

MPE 样本中 EGFR 突变率为 39.3%(116/295)。MPE 与组织之间的一致性为 87.1%(Kappa=0.71);根据组织学,MPE 中 EGFR 突变的灵敏度和特异性分别为 71.4%和 96.5%。219 例患者接受了 EGFR-TKI 治疗,MPE、组织或血浆中存在 EGFR 突变的患者客观缓解率相似(57.6%比 56.0%比 47.4%,p=0.51)。无进展生存期(8.9 个月比 9.0 个月比 7.7 个月,p=0.077)和总生存期(29.8 个月比 25.9 个月比 25.3 个月,p=0.33)也得到了类似的结果。

结论

MPE 是一种可靠的肿瘤组织替代物,可用于鉴定 EGFR 突变。即使有组织和血浆样本,MPE 也可以为晚期肺腺癌患者的 EGFR-TKI 治疗决策提供 EGFR 突变的参考。

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