Expression of constitutively activated EGFRvIII in non-small cell lung cancer
Expression of constitutively activated EGFRvIII in non-small cell lung cancer
复制标题
DOI：
10.1111/j.1349-7006.2003.tb01351.x
复制
发表时间：
2003-01-01
期刊：
影响因子：
5.7
通讯作者：
Wong, AJ
中科院分区：
文献类型：
--
作者：
Okamoto, I;Kenyon, LC;Wong, AJ
表皮生长因子受体 (EGFR) 变体 III 型（也称为 EGFRvIII、de2-7 EGFR 或 DeltaEGFR）具有胞外结构域的框内缺失，并且存在于多种类型的人类肿瘤中。由于 EGFRvIII 已被报道具有肿瘤特异性并具有致癌潜力，因此正在将其作为潜在的治疗靶点进行研究。由于肺中 EGFRvIII 的细胞特异性表达尚未得到充分记录，因此我们使用针对该变异受体的新型单克隆抗体，通过免疫组织化学方法检查了 76 个非小细胞肺癌 (NSCLC) 和 10 个非肿瘤性肺组织中 EGFRvIII 的表达。我们发现 NSCLC 中 EGFRvIII 表达增强的发生率比之前描述的要高（76 例中的 30 例，39%）。有趣的是，在肺的几种正常组织成分（例如正常支气管上皮）中也观察到了 EGFRvIII 的存在。鉴于 EGFRvIII 在 NSCLC 中的高患病率，采用新开发的磷酸特异性（激活）EGFR 抗体进行免疫组织化学分析，允许在肿瘤中可视化激活的 EGFR 和/或 EGFRvIII。这项研究首次证明人类肿瘤中表达的 EGFRvIII 被磷酸化并因此被激活。我们的结果表明 EGFRvIII 的持续激活与 NSCLC 的发病机制有关，因此 EGFRvIII 是这种具有挑战性的疾病的潜在治疗靶点。
The epidermal growth factor receptor (EGFR) variant type III (variously called EGFRvIII, de2-7 EGFR or DeltaEGFR) has an in-frame deletion of the extracellular domain and is found in numerous types of human tumors. Since EGFRvIII has been reported to be tumor-specific and has oncogenic potential, it is being investigated as a potential therapeutic target. Because the cell-specific expression of EGFRvIII in lung has not been well documented, we examined the expression of EGFRvIII in 76 non-small cell lung cancers (NSCLCs) and 10 non-neoplastic lung tissues by immunohistochemistry using a new monoclonal antibody specific for this variant receptor. We found a higher incidence (30 of 76, 39%) of enhanced EGFRvIII expression in NSCLC than previously described. Interestingly, the presence of EGFRvIII was also observed in several normal tissue components of lung (e.g., normal bronchial epithelium). Given the high prevalence of EGFRvIII in NSCLC, a newly developed phospho-specific (activated) EGFR antibody was employed for immunohistochemical analysis that permitted visualization of activated EGFR and/or EGFRvIII in tumors. This study presents evidence, for the first time, that EGFRvIII expressed in human tumors is phosphorylated and hence activated. Our results suggest that the sustained activation of EGFRvIII is implicated in the pathogenesis of NSCLC and thus EGFRvIII is a potential therapeutic target in this challenging disease.