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葡萄牙高级别胶质瘤中表皮生长因子受体(EGFR)过表达、EGFR基因扩增及EGFRvIII突变分析

Analysis of EGFR overexpression, EGFR gene amplification and the EGFRvIII mutation in Portuguese high-grade gliomas.

作者信息

Viana-Pereira Marta, Lopes José Manuel, Little Suzie, Milanezi Fernanda, Basto Diana, Pardal Fernando, Jones Chris, Reis Rui Manuel

机构信息

Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal.

出版信息

Anticancer Res. 2008 Mar-Apr;28(2A):913-20.

Abstract

BACKGROUND

Patients with malignant gliomas do not respond to any current therapy. Epidermal growth factor receptor (EGFR) controls several oncogenic processes, being frequently up-regulated in gliomas due to overexpression, gene amplification and gene mutation. EGFR inhibitors are being tried in gliomas, yet the molecular determinants of therapeutic response are unclear.

MATERIALS AND METHODS

EGFR overexpression, EGFRvIII mutation and EGFR amplification were determined by immunohistochemistry and chromogenic in situ hybridization (CISH) in 27 primary glioblastomas (GBM), 24 anaplastic oligodendrogliomas (AO) and four anaplastic oligoastrocytomas (AOA).

RESULTS

EGFR overexpression was associated with EGFR amplification, being found in 48% and 53% GBM, 33% and 40% AO and 75% and 67% AOA, respectively. EGFRvIII was found in 22% GBM, 8% AO and was absent in AOA. No association was observed between EGFR alterations and patient survival.

CONCLUSION

We characterized, for the first time, EGFR molecular alterations in Portuguese patients with malignant glioma and identified a subpopulation of patients presenting putative biomarkers for EGFR-based therapies.

摘要

背景

恶性胶质瘤患者对目前的任何治疗均无反应。表皮生长因子受体(EGFR)控制多种致癌过程,在胶质瘤中常因过表达、基因扩增和基因突变而被上调。EGFR抑制剂正在胶质瘤中进行试验,但治疗反应的分子决定因素尚不清楚。

材料与方法

通过免疫组织化学和显色原位杂交(CISH)检测27例原发性胶质母细胞瘤(GBM)、24例间变性少突胶质细胞瘤(AO)和4例间变性少突星形细胞瘤(AOA)中的EGFR过表达、EGFRvIII突变和EGFR扩增情况。

结果

EGFR过表达与EGFR扩增相关,分别在48%的GBM、33%的AO和75%的AOA中以及53%的GBM、40%的AO和67%的AOA中被发现。EGFRvIII在22%的GBM、8%的AO中被发现,在AOA中未发现。未观察到EGFR改变与患者生存之间的关联。

结论

我们首次对葡萄牙恶性胶质瘤患者的EGFR分子改变进行了特征描述,并确定了一组可能存在基于EGFR治疗生物标志物的患者亚群。

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