Overexpression of c-erbB2 is a negative prognostic factor in anaplastic astrocytomas
Overexpression of c-erbB2 is a negative prognostic factor in anaplastic astrocytomas
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DOI：
10.1186/1746-1596-5-18
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发表时间：
2010-03-23
影响因子：
2.6
通讯作者：
Torp, Sverre H.
中科院分区：
文献类型：
--
作者：
Gulati, Sasha;Ytterhus, Borgny;Torp, Sverre H.
表皮生长因子受体(EGFR)家族由四种酪氨酸激酶受体c-ErbB1-4组成，在神经胶质瘤的发生中起重要作用。本研究的目的是研究间变性星形细胞瘤中EGFR基因扩增和c-ErbB1-4受体蛋白的表达。对31例福尔马林固定切片和石蜡包埋切片进行常规免疫组织化学染色，检测c-ErbB1-4受体蛋白的表达。石蜡包埋组织用荧光原位杂交法研究EGFR基因扩增。用NCL-EGFR-384和NCL-EGFR两种单抗检测EGFR，其阳性反应率分别为97%和71%。用CB11、3B5和5A2三种单抗检测c-erbB2，其阳性反应率分别为45%、100%和52%。C-erb B3和c-erbB4的阳性表达分别为97%和74%。31例肿瘤中有9例(29%)扩增出EGFR基因。在调整了年龄、卡氏功能状态和手术切除程度后，以总生存期为因变量的COX多元回归分析显示，单抗克隆CB11检测到的c-erb B 2过表达是一个具有统计学意义的不良预后因素(P=0.004)。本研究显示了免疫组织化学方法在人脑星形细胞瘤组织切片中检测受体蛋白表达的方便性和可行性。间变性星形细胞瘤中c-ErbB1-4蛋白的同步过表达支持其在肿瘤发病机制中的作用。此外，c-erbB2的过度表达似乎预示着攻击性行为。
The epidermal growth factor receptor (EGFR) family, consisting of four tyrosine kinase receptors, c-erbB1-4, seems to be influential in gliomagenesis. The aim of this study was to investigate EGFR gene amplification and expression of c-erbB1-4 receptor proteins in human anaplastic astrocytomas. Formalin-fixed and paraffin-embedded sections from 31 cases were investigated by standard immunohistochemical procedures for expression of c-erbB1-4 receptor proteins using commercial antibodies. EGFR gene amplification was studied by fluorescence in situ hybridization using paraffin-embedded tissues. Two monoclonal antibodies, NCL-EGFR-384 and NCL-EGFR, were used for EGFR detection and they displayed positive immunoreactivity in 97% and 71%, respectively. For c-erbB2 detection three monoclonal antibodies, CB11, 3B5, and 5A2, were applied and they displayed positive immunoreactivity in 45%, 100%, and 52%, respectively. Positive immunostaining for c-erbB3 and c-erbB4 was encountered in 97% and 74%, respectively. The EGFR gene was amplified in 9 out of 31 tumors (29%). After adjusting for age, Karnofsky performance status, and extent of surgical resection, Cox multiple regression analysis with overall survival as the dependent variable revealed that c-erbB2 overexpression detected by the monoclonal antibody clone CB11 was a statistically significant poor prognostic factor (P = 0.004). This study shows the convenience and feasibility of immunohistochemistry when determining the expression of receptor proteins in tissue sections of human astrocytomas. The synchronous overexpression of c-erbB1-4 proteins in anaplastic astrocytomas supports their role in the pathogenesis of these tumors. Further, c-erbB2 overexpression seems to predict aggressive behaviour.