Prognostic and predictive implications of HER2/ERBB2/neu gene mutations in lung cancers
Prognostic and predictive implications of HER2/ERBB2/neu gene mutations in lung cancers
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DOI：
10.1016/j.lungcan.2011.01.014
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发表时间：
2011-10-01
期刊：
影响因子：
5.3
通讯作者：
Mitsudomi, Tetsuya
中科院分区：
文献类型：
--
作者：
Tomizawa, Kenji;Suda, Kenichi;Mitsudomi, Tetsuya
背景资料：据报道，人EGF受体2（HER 2）基因（也称为ERBB 2或neu）激酶结构域的激活突变存在于一小部分肺腺癌中。然而，其预后和预测的影响尚未established.Patients和方法：我们研究了504日本肺癌患者接受肺切除术的HER 2突变直接测序，并评估其预后和预测的影响。更新的预后数据，14例日本患者与HER 2突变从以前的两个reports.Results：HER 2突变被确定在13 504例（2.6%）。与EGFR突变患者一样，HER 2突变患者常见于女性、非吸烟者和腺癌患者。当仅限于不吸烟的腺癌或腺鳞癌亚组，没有EGFR突变，HER 2突变的频率为14.1%（11/78）。与携带EGFR突变的患者和携带EGFR和HER 2野生型的患者相比，携带HER 2突变的患者的总生存期无差异。在HER 2突变患者中，TP 53突变的3例患者中有2例死于该病，而非TP 53突变的13例患者中有1例死于该病，表明TP 53突变具有负面预后作用。3例HER 2突变患者对含铂化疗和EGFR-TKI无应答。值得注意的是，一个最常见的HER 2突变，YVMA 776 - 779 ins的患者，响应曲妥珠单抗加长春瑞滨后失败的多轮铂类化疗和吉非替尼。结论：HER 2突变存在于一个子集的肺癌患者具有不同的临床特征。HER 2突变与肺癌患者的预后无关。HER 2突变患者可能从抗HER 2治疗中获益。(C)2011爱思唯尔爱尔兰有限公司保留所有权利。
Background: Activating mutation in the kinase domain of the human EGF receptor 2 (HER2) gene (also known as ERBB2 or neu) is reported to be present in a small fraction of lung adenocarcinomas. However its prognostic and predictive implications are not yet established.Patients and methods: We examined 504 Japanese lung cancer patients who underwent pulmonary resection for HER2 mutations by direct sequencing and evaluated their prognostic and predictive implications. Updated prognostic data of 14 Japanese patients with HER2 mutation from previous two reports were also gathered.Results: HER2 mutations were identified in 13 of 504 cases (2.6%). Patients with HER2 mutations were common in female, nonsmokers and adenocarcinomas as those with EGFR mutations. When confined to the subgroup of nonsmokers with adenocarcinoma or adenosquamous cell carcinoma without EGFR mutations, the frequency of HER2 mutations was 14.1% (11/78). There was no difference in the overall survival of patients with HER2 mutations, compared with patients harboring EGFR mutations and patients harboring wild types for both EGFR and HER2. Within the patients with HER2 mutation, two of three with TP53 mutation and one of 13 without TP53 mutation died of the disease, suggesting negative prognostic role of the TP53 mutation. Three patients with HER2 mutations did not respond to platinum-based chemotherapy and EGFR-TKIs. Of note, one patient with the most common HER2 mutations, YVMA776-779ins, responded to trastuzumab plus vinorelbine after failure of multiple round of platinum-based chemotherapy and gefitinib.Conclusion: HER2 mutations are present in a subset of patients with lung cancer having distinct clinical features. HER2 mutations were not associated with the prognosis of patients with lung cancers. Patients with HER2 mutations might benefit from anti-HER2 therapy. (C) 2011 Elsevier Ireland Ltd. All rights reserved.