Department of Neurosurgery, Medical University of Silesia in Katowice, Portland.
Folia Neuropathol. 2011;49(1):28-38.
Epidermal growth factor receptor (EGFR) gene amplification and protein expression in malignant gliomas (anaplastic astrocytoma, AA and glioblastoma, GBL) were suggested to be correlated with the degree of malignancy. Large deletions within the EGFR gene occur frequently in glioma patients. The aim of our study was to analyse EGFR gene expression by real-time PCR by three different amplicons located across the gene and relate it to the age of patients and EGFR mutation status.
We analysed EGFR gene expression in 75 patients, median age 58 years (range 28-75), 52% of glioblastomas, 39% of anaplastic astrocytomas and 9% of low grade gliomas. EGFR expression was measured by real-time PCR, three amplicons located at exons 2-3, 13-14, and 17-18 junctions were analysed, gene expression was normalized by 18S RNA expression. EGFRvIII deletion was detected by RT-PCR.
EGFR was found to be expressed in 61.8% of brain gliomas, with strongly positive expression in 12.2% of them. We simultaneously analysed by RT-PCR the EGFRvIII status and found the deletion in 21.3% of tumours. In our group EGFRvIII mutation was significantly more frequent in patients older than 50 years of age (48.6%) than in younger patients (23.5%, p < 0.05). When only GBL patients were assessed, none of the patients younger than 50 years of age had EGFRvIII mutation, whereas in the older subgroup they constituted 36.67% of subjects. We observed that younger patients (below 50 yrs) had slightly lower EGFR expression in comparison to older patients, but this difference was not statistically significant.
As nearly 1/3 of high grade gliomas do not demonstrate abnormal gene expression levels, EGFR status should be taken into account in any targeted therapy attempt. The significance of EGFR axis-related differences between young and old glioma patients and their impact on the prognosis warrant further study.
表皮生长因子受体（EGFR）基因扩增和蛋白表达在恶性胶质瘤（间变性星形细胞瘤，AA 和胶质母细胞瘤，GBL）中被认为与恶性程度相关。EGFR 基因内的大片段缺失在胶质瘤患者中经常发生。我们的研究目的是通过位于基因内的三个不同扩增子，实时 PCR 分析 EGFR 基因表达，并将其与患者年龄和 EGFR 突变状态相关联。
我们分析了 75 例患者的 EGFR 基因表达，中位年龄 58 岁（范围 28-75），52%为胶质母细胞瘤，39%为间变性星形细胞瘤，9%为低级别胶质瘤。通过实时 PCR 测量 EGFR 表达，分析位于外显子 2-3、13-14 和 17-18 交界处的三个扩增子，通过 18S RNA 表达对基因表达进行归一化。通过 RT-PCR 检测 EGFRvIII 缺失。
在 61.8%的脑胶质瘤中发现 EGFR 表达，其中 12.2%表达强烈阳性。我们同时通过 RT-PCR 分析 EGFRvIII 状态，发现 21.3%的肿瘤存在缺失。在我们的研究组中，年龄大于 50 岁的患者 EGFRvIII 突变的频率明显高于年龄较小的患者（48.6%比 23.5%，p<0.05）。仅评估 GBL 患者时，年龄小于 50 岁的患者无一例 EGFRvIII 突变，而在年龄较大的亚组中，这一比例为 36.67%。我们观察到，年轻患者（<50 岁）的 EGFR 表达略低于年长患者，但差异无统计学意义。
由于近 1/3 的高级别胶质瘤没有表现出异常的基因表达水平，因此在任何靶向治疗尝试中都应考虑 EGFR 状态。年轻和年长的胶质瘤患者之间 EGFR 轴相关差异的意义及其对预后的影响值得进一步研究。
