Usefulness of EGFR mutation screening in pleural fluid to predict the clinical outcome of gefitinib treated patients with lung cancer
Usefulness of EGFR mutation screening in pleural fluid to predict the clinical outcome of gefitinib treated patients with lung cancer
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DOI：
10.1002/ijc.22190
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发表时间：
2006-11-15
影响因子：
6.4
通讯作者：
Date, Hiroshi
中科院分区：
文献类型：
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作者：
Soh, Junichi;Toyooka, Shinichi;Date, Hiroshi
表皮生长因子受体（EGFR）基因突变在非小细胞肺癌（NSCLC）中的重要性已被认识，需要建立包括样本种类在内的突变筛查体系。在这里，我们研究了61例非小细胞肺癌患者的胸水样本中EGFR突变的状态，采用直接测序，非富集PCR，多核苷酸富集PCR和肽核酸锁核酸（PNA-LNA）PCR钳位分析。富集突变基因的PCR方法检测到16例突变病例。其中，非富集PCR法未能检测到3例突变病例。在突变富集PCR和PNA-LNA PCR钳夹试验之间的差异方面，3例外显子19缺失仅用突变富集PCR检测，而L 858 R突变无差异。直接测序和非富集PCR检测结果无差异。我们还将EGFR突变与吉非替尼治疗的29例患者的临床结局相关联。EGFR突变10例，部分缓解7例，无变化3例。在EGFR野生型病例中，10例显示NC，9例显示疾病进展。EGFR突变病例中的应答者明显多于野生型病例（p < 0.0001）。EGFR突变病例的总生存期（p = 0.0092）和无进展生存期（p = 0.018）显著长于野生型。总之，我们使用4种检测方法评价了胸腔积液中EGFR突变筛查的实用性，这些检测方法显示了检测设计引起的一些差异。作为临床重要性，胸水中的EGFR突变状态可以作为吉非替尼治疗NSCLC病例的有利结局的生物标志物。(c)2006 Wiley-Liss，Inc.
The importance of epidermal growth factor receptor (EGFR) gene mutation has been recognized in nonsmall cell lung cancer (NSCLC), requiring the standardization of mutation screening system including the kind of samples. Here, we examined the EGFR mutation status in 61 pleural fluid samples from NSCLC cases using direct sequencing, nonenriched PCR, mutant-enriched PCR and peptide nucleic acid-locked nucleic acid (PNA-LNA) PCR clamp assay. The mutant-enriched PCR assay detected 16 mutant cases. Among them, the nonenriched PCR assay failed to detect 3 mutant cases. Regarding the discrepancy between mutant-enriched PCR and PNA-LNA PCR clamp assays, 3 cases of exon19-deletions were detected only by mutant-enriched PCR assay and no difference at the L858R mutation. There was no difference in results between direct sequencing and nonenriched PCR assay. We also correlated the EGFR mutation with clinical outcome of gefitinib-treated 29 cases. EGFR mutations were present in 10 cases, revealing 7 partial response and 3 no change (NC). In EGFR wild-type cases, 10 revealed NC and 9 progressive disease. The responders were significantly more frequent among the EGFR mutant cases than among the wild-type (p < 0.0001). Overall survival (p = 0.0092) and progression-free survival (p = 0.018) were significantly longer among the EGFR mutant cases than among the wild-type. In summary, we evaluated the utility of EGFR mutation screening in pleural fluid using 4 assays that showed some discrepancies arising from the designs of the assays. As clinical importance, the EGFR mutation status in pleural fluid can be a biomarker for the favorable outcome of gefitinib-treated NSCLC cases. (c) 2006 Wiley-Liss, Inc.