Prevalence, Clinicopathologic Characteristics, and Molecular Associations of EGFR Exon 20 Insertion Mutations in East Asian Patients with Lung Adenocarcinoma
Prevalence, Clinicopathologic Characteristics, and Molecular Associations of EGFR Exon 20 Insertion Mutations in East Asian Patients with Lung Adenocarcinoma
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东亚肺腺癌患者 EGFR 外显子 20 插入突变的患病率、临床病理特征和分子关联
DOI：
10.1245/s10434-013-3452-1
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发表时间：
2014-12-01
影响因子：
3.7
通讯作者：
Chen, Haiquan
中科院分区：
文献类型：
--
作者：
Pan, Yunjian;Zhang, Yang;Chen, Haiquan
目的明确表皮生长因子受体（EGFR）20号外显子插入突变在东亚肺腺癌患者中的患病率、临床病理特征和分子相关性。EGFR和HER 2拷贝数变异; ErbB家族成员包括EGFR、HER 2和HER 3的总蛋白表达和磷酸化（p）蛋白表达;下游信号传导分子包括Akt和Erk的磷酸化蛋白表达;结果EGFR 20号外显子插入突变阳性率为2.9%，的肺腺癌和所有EGFR突变的4.7%。与携带经典激活EGFR突变的患者相比，携带20号外显子插入突变的肺腺癌的特征是诊断时年龄显著更小（20号外显子插入与L 858 R相比，P = 0.032）和无复发生存期更短[20号外显子插入与19号外显子缺失相比，P = 0.045]。在分子水平上，携带20号外显子插入突变的样本的磷酸化（p）-EGFR（P 0.001）和HER 3（P = 0.016）表达较低。此外，EGFR 20号外显子插入突变的肺腺癌中p-Akt的表达明显增高（P = 0.007），而p-Erk的表达明显降低（P = 0.009）。与经典EGFR激活突变患者相比，该亚组显示出独特的临床病理学特征，对EGFR的分子依赖性较低，以及不同的通路激活模式。
PurposeTo define the prevalence, clinicopathologic characteristics and molecular associations of epidermal growth factor receptor (EGFR) exon 20 insertion mutations in East Asian lung adenocarcinoma patients.MethodsA total of 1,086 lung adenocarcinomas were sequenced for EGFR mutations. EGFR and HER2 copy number variations; total and phosphorylated (p) protein expression of ErbB family members including EGFR, HER2, and HER3; phosphorylated protein expression of downstream signaling molecules including Akt and Erk; and clinicopathologic features in lung adenocarcinomas with EGFR exon 20 insertion mutations were all investigated.ResultsEGFR exon 20 insertion mutations were present in 2.9 % of lung adenocarcinomas and 4.7 % of all the EGFR mutations. Compared to those with classic activating EGFR mutations, lung adenocarcinomas with exon 20 insertion mutations were characterized by significantly younger age at diagnosis (P = 0.032 for exon 20 insertions vs. L858R) and shorter relapse-free survival [P = 0.045 for exon 20 insertions versus (vs) exon 19 deletions]. Molecularly, samples harboring exon 20 insertion mutations had lower expression of phosphorylated (p)-EGFR (P < 0.001) and HER3 (P = 0.016). In addition, higher expression of p-Akt (P = 0.007) and lower expression of p-Erk (P = 0.009) were observed in tumors with exon 20 insertion mutations.ConclusionsLung adenocarcinomas with EGFR exon 20 insertion mutations were present in a substantial proportion. This subset showed distinct clinicopathologic features, less dependence on EGFR molecularly, and different pathway activation patterns compared to those with classic EGFR activating mutations.