Expression of epidermal growth factor variant III (EGFRvIII) in pediatric diffuse intrinsic pontine gliomas
Expression of epidermal growth factor variant III (EGFRvIII) in pediatric diffuse intrinsic pontine gliomas
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DOI：
10.1007/s11060-012-0842-3
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发表时间：
2012-07-01
影响因子：
3.9
通讯作者：
Wong, Albert J.
中科院分区：
文献类型：
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作者：
Li, Gordon;Mitra, Siddhartha S.;Wong, Albert J.
尽管在过去的20年中进行了大量的临床试验，但诊断为弥漫性内在脑桥胶质瘤（DIPG）的儿童的总生存期仍然为9-10个月。放射治疗是唯一有效的治疗方法，需要新的治疗方法。表皮生长因子受体变体III（EGFRvIII）是表皮生长因子受体的最常见变体，并且在许多肿瘤类型中表达，但很少在正常组织中发现。靶向EGFRvIII的肽疫苗目前正在进行3期临床试验，用于治疗新诊断的胶质母细胞瘤（GBM），这种变体受体首次被发现的肿瘤。在这项研究中，我们评估了EGFRvIII表达的儿科DIPG样本使用免疫组化的双重亲和纯化抗体提出的抗EGFRvIII肽。儿科DIPG组织学样本染色显示9例中有4例表达，染色模式与EGFRvIII转染细胞以及成人试验GBM中观察到的一致。此外，通过RT-PCR、蛋白质印迹分析和流式细胞术分析死后立即收集的肿瘤样品和培养物中的DIPG细胞证实了EGFRvIII表达。因此，我们能够检测到EGFRvIII表达的11例DIPG中的6例。这些数据表明，EGFRvIII值得作为这些致命的儿科肿瘤的靶点进行研究。
Despite numerous clinical trials over the past 2 decades, the overall survival for children diagnosed with diffuse intrinsic pontine glioma (DIPG) remains 9-10 months. Radiation therapy is the only treatment with proven effect and novel therapies are needed. Epidermal growth factor receptor variant III (EGFRvIII) is the most common variant of the epidermal growth factor receptor and is expressed in many tumor types but is rarely found in normal tissue. A peptide vaccine targeting EGFRvIII is currently undergoing investigation in phase 3 clinical trials for the treatment of newly diagnosed glioblastoma (GBM), the tumor in which this variant receptor was first discovered. In this study, we evaluated EGFRvIII expression in pediatric DIPG samples using immunohistochemistry with a double affinity purified antibody raised against the EGFRvIII peptide. Staining of pediatric DIPG histological samples revealed expression in 4 of 9 cases and the pattern of staining was consistent with what has been seen in EGFRvIII transfected cells as well as GBMs from adult trials. In addition, analysis of tumor samples collected immediately post mortem and of DIPG cells in culture by RT-PCR, western blot analysis, and flow cytometry confirmed EGFRvIII expression. We were therefore able to detect EGFRvIII expression in 6 of 11 DIPG cases. These data suggest that EGFRvIII warrants investigation as a target for these deadly pediatric tumors.