Division of Thoracic Oncology, National Cancer Center Hospital East, Chiba.
Department of Thoracic Oncology, Hyogo Cancer Center, Hyogo.
Ann Oncol. 2012 Nov;23(11):2914-2919. doi: 10.1093/annonc/mds121. Epub 2012 Jul 9.
Epidermal growth factor receptor (EGFR) mutation is predictive for the efficacy of EGFR tyrosine kinase inhibitors in advanced non-small-cell lung cancer (NSCLC) treatment. We evaluated the performance, sensitivity, and concordance between five EGFR tests.
DNA admixtures (n = 34; 1%-50% mutant plasmid DNA) and samples from NSCLC patients [116 formalin-fixed paraffin-embedded (FFPE) tissue, 29 matched bronchofiberscopic brushing (BB) cytology, and 20 additional pleural effusion (PE) cytology samples] were analyzed. EGFR mutation tests were PCR-Invader, peptide nucleic acid-locked nucleic acid PCR clamp, direct sequencing, Cycleave, and Scorpion Amplification Refractory Mutation System (ARMS). Analysis success, mutation status, and concordance rates were assessed.
All tests except direct sequencing detected four mutation types at ≥1% mutant DNA. Analysis success rates were 91.4%-100% (FFPE) and 100% (BB and PE cytology), respectively. Inter-assay concordance rates of successfully analyzed samples were 94.3%-100% (FFPE; kappa coefficients: 0.88-1.00), 93.1%-100% (BB cytology; 0.86-1.00), and 85.0%-100% (PE cytology; 0.70-1.00), and 93.1%-96.6% (0.86-0.93) between BB cytology and matched FFPE.
All EGFR assays carried out comparably in the analysis of FFPE and cytology samples. Cytology-derived DNA is a viable alternative to FFPE samples for analyzing EGFR mutations.
表皮生长因子受体（EGFR）突变可预测 EGFR 酪氨酸激酶抑制剂在晚期非小细胞肺癌（NSCLC）治疗中的疗效。我们评估了五种 EGFR 检测方法的性能、敏感性和一致性。
对 DNA 混合物（n=34；1%-50%突变质粒 DNA）和 NSCLC 患者的样本[116 例福尔马林固定石蜡包埋（FFPE）组织、29 例配对支气管纤维镜刷取细胞学（BB）、20 例胸腔积液细胞学（PE）]进行分析。EGFR 突变检测采用 PCR-Invader、肽核酸锁核酸 PCR 夹、直接测序、Cycleave 和 Scorpion 扩增阻滞突变系统（ARMS）。评估分析成功率、突变状态和一致性率。
除直接测序外，所有检测方法均能在 1%以上的突变 DNA 中检测到四种突变类型。FFPE 的分析成功率分别为 91.4%-100%和 100%（BB 和 PE 细胞学）。成功分析样本的组内一致性率分别为 94.3%-100%（FFPE；kappa 系数：0.88-1.00）、93.1%-100%（BB 细胞学；0.86-1.00）、85.0%-100%（PE 细胞学；0.70-1.00）和 93.1%-96.6%（0.86-0.93）（BB 细胞学与配对 FFPE）。
所有 EGFR 检测方法在 FFPE 和细胞学样本分析中表现相当。细胞学衍生的 DNA 是分析 EGFR 突变的 FFPE 样本的可行替代物。
