Epidermal Growth Factor Receptor Variant III (EGFRvIII) Positivity in EGFR-Amplified Glioblastomas: Prognostic Role and Comparison between Primary and Recurrent Tumors
Epidermal Growth Factor Receptor Variant III (EGFRvIII) Positivity in EGFR-Amplified Glioblastomas: Prognostic Role and Comparison between Primary and Recurrent Tumors
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DOI：
10.1158/1078-0432.ccr-17-0890
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发表时间：
2017-11-15
影响因子：
11.5
通讯作者：
Weller, Michael
中科院分区：
文献类型：
--
作者：
Felsberg, Joerg;Hentschel, Bettina;Weller, Michael
目的：大约40%的胶质母细胞瘤扩增了EGFR基因，其中大约一半的肿瘤表达EGFRvIII变体。EGFRvIII在EGFR扩增的胶质母细胞瘤患者的预后作用和EGFRvIII在复发与原发性胶质母细胞瘤表达的变化仍然存在争议，但这些数据是高度相关的EGFRvIII靶向therapy.Experimental Design：EGFR扩增的胶质母细胞瘤从106例患者进行了评估EGFRvIII阳性。在40例EGFR扩增肿瘤患者和33例EGFR非扩增肿瘤患者中评价了EGFR扩增和EGFRvIII状态从原发性到复发性胶质母细胞瘤的变化。在27例患者中评估EGFR单核苷酸变异（SNV）。数据与结果相关，并在150例胶质母细胞瘤患者的癌症基因组图谱（TCGA）consortion.Results验证：60 106 EGFR扩增胶质母细胞瘤EGFRvIII阳性（56.6%）。EGFRvIII阳性与不同的无进展生存期或总生存期无关。40例EGFR扩增原发性肿瘤患者中有35例（87.5%）的EGFR vIII状态在复发时无变化。复发时，4例患者失访，1例患者获得EGFRvIII阳性。33例EGFR非扩增胶质母细胞瘤在复发时均未获得EGFR扩增或EGFRvIII。EGFR SNVs在EGFR扩增的肿瘤中很常见，但与生存率无关。结论：EGFR扩增的胶质母细胞瘤患者中，EGFRvIII和EGFR SNVs不具有预后意义。EGFR扩增在复发性胶质母细胞瘤中保留。大多数EGFRvIII阳性胶质母细胞瘤在复发时保持EGFRvIII阳性。然而，EGFRvIII表达可能会改变一个子集的患者在复发，因此重复活检与EGFRvIII状态的重新评估建议复发性胶质母细胞瘤患者接受EGFRvIII靶向药物。(C)2017年AACR。
Purpose: Approximately 40% of all glioblastomas have amplified the EGFR gene, and about half of these tumors express the EGFRvIII variant. The prognostic role of EGFRvIII in EGFR-amplified glioblastoma patients and changes in EGFRvIII expression in recurrent versus primary glioblastomas remain controversial, but such data are highly relevant for EGFRvIII-targeted therapies.Experimental Design: EGFR-amplified glioblastomas from 106 patients were assessed for EGFRvIII positivity. Changes in EGFR amplification and EGFRvIII status from primary to recurrent glioblastomas were evaluated in 40 patients with EGFR-amplified tumors and 33 patients with EGFR-nonamplified tumors. EGFR single-nucleotide variants (SNV) were assessed in 27 patients. Data were correlated with outcome and validated in 150 glioblastoma patients from The Cancer Genome Atlas (TCGA) consortium.Results: Sixty of 106 EGFR-amplified glioblastomas were EGFRvIII-positive (56.6%). EGFRvIII positivity was not associated with different progression-free or overall survival. EGFRvIII status was unchanged at recurrence in 35 of 40 patients with EGFR-amplified primary tumors (87.5%). Four patients lost and one patient gained EGFRvIII positivity at recurrence. None of 33 EGFR-nonamplified glioblastomas acquired EGFR amplification or EGFRvIII at recurrence. EGFR SNVs were frequent in EGFRamplified tumors, but were not linked to survival.Conclusions: EGFRvIII and EGFR SNVs are not prognostic in EGFR-amplified glioblastoma patients. EGFR amplification is retained in recurrent glioblastomas. Most EGFRvIII-positive glioblastomas maintain EGFRvIII positivity at recurrence. However, EGFRvIII expression may change in a subset of patients at recurrence, thus repeated biopsy with reassessment of EGFRvIII status is recommended for patients with recurrent glioblastoma to receive EGFRvIII-targeting agents. (C) 2017 AACR.