Assessment of epidermal growth factor receptor mutation by endobronchial ultrasound-guided transbronchial needle aspiration
Assessment of epidermal growth factor receptor mutation by endobronchial ultrasound-guided transbronchial needle aspiration
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DOI：
10.1378/chest.07-0095
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发表时间：
2007-08-01
期刊：
影响因子：
9.6
通讯作者：
Fujisawa, Takehiko
中科院分区：
文献类型：
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作者：
Nakajima, Takahiro;Yasufuku, Kazuhiro;Fujisawa, Takehiko
背景资料：表皮生长因子受体（EGFR）体细胞突变的存在预测了EGFR酪氨酸激酶抑制剂（TKI）的有效性。如果能在活检样本中检测到EGFR突变，那将是理想的，因为大多数非小细胞肺癌患者在出现时是不能手术的。我们报告了支气管内超声引导下经支气管针吸活检（EBUS-TBNA）对肺癌淋巴结分期的有效性。EBUS-TBNA能够对组织学核心进行取样，可用于遗传分析。方法：本研究的目的是开发和分析的EBUS-TBNA获得的样本中检测EGFR突变的可行性。46例原发性肺癌患者入组本研究，其中EBUSTBNA诊断为肺门和/或纵隔淋巴结转移性腺癌。从石蜡包埋的样本中提取DNA，并使用新开发的环杂交迁移率变动分析在外显子19和21中分析EGFR突变。结果通过直接测序证实。结果如下：43例病例符合分析条件，11例病例中检测到EGFR突变（25.6%）; 1例为外显子19的框内缺失（E746-A750 del），9例为外显子21的点突变（L 858 R），1例为双点突变（L 858 R + L 861 V）。所有EGFR突变病例均通过直接测序确认。结论：EBUSTBNA法可检测转移性淋巴结中EGFR突变。EBUS-TBNA允许对淋巴结内的肿瘤细胞进行遗传评估，并可能在不久的将来为我们提供EGFR-TKI治疗的指征。
Background: The presence of somatic mutations in epidermal growth factor receptor (EGFR) predicts the effectiveness of EGFR tyrosine kinase inhibitors (TKIs). it would be ideal if an EGFR mutation could be detected in biopsy samples, since the majority of non-small cell lung cancer patients are inoperable at the time of presentation. We have reported the usefulness of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for the lymph node staging of lung cancer. EBUS-TBNA enables the sampling of histologic cores, which can be used for genetic analysis. Methods: The purpose of this study was to develop and analyze the feasibility of detecting EGFR mutations in samples obtained by EBUS-TBNA. Forty-six patients with primary lung cancer in whom metastatic adenocarcinoma in the hilar and/or mediastinal lymph node was diagnosed by EBUSTBNA were enrolled into the study. DNA was extracted from paraffin-embedded samples, and the EGFR mutation was analyzed in exons 19 and 21 using a newly developed loop-hybrid mobility shift assay. The results were confirmed by direct sequencing. Results: Forty-three cases were eligible for analysis and in 11 cases, EGFR mutation (25.6%) was detected; one case was an in-frame deletion (E746-A750del) of exon 19, nine cases were point mutations (L858R) of exon 21, and one case was a double point mutation (L858R+L861V). All cases with EGFR mutations were confirmed by direct sequencing. Conclusions: EGFR mutation can easily be detected in metastatic lymph nodes sampled by EBUSTBNA.'EBUS-TBNA allows genetic evaluations of tumor cells within the lymph node and may provide us with indications for EGFR-TKI therapy in the near future.