Prognostic value of epidermal growth factor receptor in patients with glioblastoma multiforme.
Prognostic value of epidermal growth factor receptor in patients with glioblastoma multiforme.
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发表时间：
2003-10
期刊：
影响因子：
11.2
通讯作者：
N. Shinojima;K. Tada;S. Shiraishi;T. Kamiryo;M. Kochi;Hideo Nakamura;K. Makino;H. Saya;H. Hirano;J. Kuratsu;K. Oka;Y. Ishimaru;Y. Ushio
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作者：
N. Shinojima;K. Tada;S. Shiraishi;T. Kamiryo;M. Kochi;Hideo Nakamura;K. Makino;H. Saya;H. Hirano;J. Kuratsu;K. Oka;Y. Ishimaru;Y. Ushio
多形性胶质母细胞瘤（GBM）通常涉及表皮生长因子受体（EGFR）基因的扩增和改变，导致各种突变的过表达，包括最常见的突变EGFRvIII，以及野生型EGFR （EGFRwt）。为了检验EGFR的预后价值，我们回顾性分析了87例参加临床试验的新诊断的成年幕上GBM患者的治疗结果与EGFR基因之间的关系。使用三种单克隆抗体（EGFR为EGFR的EGFR.25， EGFRwt为EGFR.113， EGFRvIII为EGFR. DH8.3），通过Southern印迹法评估EGFR基因状态，免疫组织化学法评估EGFR的表达。87例GBM患者中有40例（46%）检测到EGFR扩增；其中39例（97.5%）EGFR过表达。另一方面，47例无EGFR扩增的患者中有46例（97.9%）未出现EGFR过表达。EGFR扩增与EGFR过表达密切相关（P < 0.0001）。EGFRwt在40例有EGFR扩增的患者中有27例（67.5%）过表达，无EGFR扩增的患者中无EGFRwt过表达（P < 0.0001）。同样，EGFRvIII在40例有EGFR扩增的患者中有18例（45.0%）过表达，在47例无EGFR扩增的患者中有4例（8.5%）过表达（P < 0.0001）。8例（20%）的EGFR扩增/EGFR过表达患者既不表现出EGFRwt过表达，也不表现出EGFRvIII过表达，这表明他们过度表达了其他类型的EGFR。多因素分析表明，EGFR扩增是所有患者总生存（OS）的一个独立、显著、不利的预测因子（P = 0.038, HR = 1.67）。关于年龄与EGFR预后的关系，EGFR基因状态在年轻患者中是一个更重要的预测指标，特别是在<60岁的患者中（P = 0.0003, HR = 3.15），而在老年患者中则不是这样。另一方面，EGFRvIII过表达并不能预测OS。然而，在EGFR扩增的患者中，多因素分析显示，EGFRvIII过表达是OS的一个独立的、显著的不良预后因素（P = 0.0044, HR = 2.71）。这一发现表明，在EGFR扩增的情况下，EGFRvIII过表达是生存预后不良的最强指标。在GBM患者中，EGFR对预测生存具有重要的预后价值，EGFRvIII的过表达和扩增在增强致瘤性中起重要作用。
Glioblastoma multiforme (GBM) frequently involves amplification and alteration of the epidermal growth factor receptor (EGFR) gene, resulting in overexpression of varied mutations, including the most common mutation, EGFRvIII, as well as wild-type EGFR (EGFRwt). To test the prognostic value of EGFR, we retrospectively analyzed the relationship between treatment outcomes and the EGFR gene in 87 newly diagnosed adult patients with supratentorial GBM enrolled in clinical trials. The EGFR gene status was assessed by Southern blots and EGFR expression by immunohistochemistry using three monoclonal antibodies (EGFR.25 for EGFR, EGFR.113 for EGFRwt, and DH8.3 for EGFRvIII). EGFR amplification was detected in 40 (46%) of the 87 GBM patients; in 39 (97.5%) of these, EGFR was overexpressed. On the other hand, in 46 of 47 patients without EGFR amplification (97.9%), no EGFR overexpression was present. There was a close correlation between EGFR amplification and EGFR overexpression (P < 0.0001). EGFRwt was overexpressed in 27 of the 40 (67.5%) patients with, and in none without, EGFR amplification (P < 0.0001). Similarly, EGFRvIII was overexpressed in 18 (45.0%) of 40 patients with and in 4 (8.5%) of 47 patients without EGFR amplification (P < 0.0001). The finding that 8 (20%) of the patients with EGFR amplification/EGFR overexpression manifested overexpression of neither EGFRwt nor EGFRvIII indicates that they overexpressed other types of EGFR. Multivariate analysis demonstrated that EGFR amplification was an independent, significant, unfavorable predictor for overall survival (OS) in all patients (P = 0.038, HR = 1.67). With respect to the relationship of age to EGFR prognostication, the EGFR gene status was a more significant prognosticator in younger patients, particularly in those <60 years (P = 0.0003, HR = 3.15), whereas not so in older patients. EGFRvIII overexpression, on the other hand, was not predictive for OS. However, in patients with EGFR amplification, multivariate analysis revealed that EGFRvIII overexpression was an independent, significant, poor prognostic factor for OS (P = 0.0044, HR = 2.71). This finding indicates that EGFRvIII overexpression in the presence of EGFR amplification is the strongest indicator of a poor survival prognosis. In GBM patients, EGFR is of significant prognostic value for predicting survival, and the overexpression of EGFRvIII with amplification plays an important role in enhanced tumorigenicity.