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EGFR and EGFRvIII analysis in glioblastoma as therapeutic biomarkers

机译:胶质母细胞瘤中的EGFR和EGFRvIII分析作为治疗性生物标志物

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Introduction. EGFR and EGFRvIII analysis is of current interest because of new EGFRvIII vaccine trials opened in the UK. EGFR activation promotes cellular proliferation via activation of MAPK and PI3K-Akt pathways. EGFRvIII is the most common variant resulting from an in-frame deletion of 801 bp, leading to constitutively active EGFR. Method. 51 glioblastoma samples from a cohort of 50 patients were tested for EGFR amplification by FISH and immunohistochemistry and EGFRvIII expression by reverse-transcriptase PCR (RT-PCR), and immunohistochemistry. EGFR and EGFRvIII expression was compared with Overall Survival in the cohort. Results. Overall 22/51 samples (43%) were positive for EGFR, 16/51 (31%) were positive for EGFRvIII and 13/51 (25%) were positive for both. 9/51 cases (18%) were positive for EGFR alone, and 3/51 (6%) were positive for EGFRvIII alone. Of the EGFR positive cases, 22/51 (43%) were positive by FISH, 24/51 (47%) were positive by IHC and 2/51 (4%) were discrepant between methods (positive by IHC but non-amplified by FISH). Of the EGFRvIII positive cases, 16/51 (31%) were positive by RT-PCR, 17/51 (33%) were positive by IHC and 1/51 (2%) sample was discrepant (positive by IHC but not by RT-PCR). Neither EGFRvIII or EGFR are predictive of overall survival in this cohort. Conclusion. In our cohort, 25/51 (49%) of GBM showed EGFR alterations, including 16/51 (31%) with EGFRvIII. There was high concordance between IHC and FISH (96%) and IHC and RT-PCR (98%) as diagnostic methods. Neither EGFR or EGFRvIII is predictive of overall survival in this cohort. These results are key for selecting patients for novel individualised anti-EGFR therapies.
机译:介绍。由于在英国开展了新的EGFRvIII疫苗试验,因此对EGFR和EGFRvIII的分析引起了人们的关注。 EGFR激活通过激活MAPK和PI3K-Akt途径促进细胞增殖。 EGFRvIII是最常见的变异,是由801 bp的框内缺失导致的,从而导致了组成型活性EGFR。方法。通过FISH和免疫组织化学测试了来自50名患者的51个胶质母细胞瘤样品的EGFR扩增,并通过逆转录酶PCR(RT-PCR)和免疫组织化学测试了EGFRvIII的表达。将队列中的EGFR和EGFRvIII表达与总生存期进行比较。结果。总体上22/51个样本(43%)EGFR阳性,16/51(31%)EGFRvIII阳性,13/51(25%)两者均为阳性。 9/51例(18%)仅EGFR阳性,3/51例(6%)EGFRvIII阳性。在EGFR阳性病例中,FISH阳性率为22/51(43%),IHC阳性为24/51(47%),两种方法之间的差异为2/51(4%)(IHC阳性但未扩增)鱼)。在EGFRvIII阳性病例中,RT-PCR阳性率为16/51(31%),IHC阳性为17/51(33%),1/51(2%)样品差异较大(IHC阳性但RT不阳性) -PCR)。 EGFRvIII或EGFR均不能预测该队列的总生存期。结论。在我们的队列中,GBM的25/51(49%)显示EGFR改变,包括EGFRvIII的16/51(31%)。 IHC和FISH(96%)与IHC和RT-PCR(98%)作为诊断方法之间具有很高的一致性。 EGFR或EGFRvIII均不能预测该队列的总体生存。这些结果是选择患者进行新型个体化抗EGFR治疗的关键。

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