Epidermal growth factor receptor family (EGFR, ErbB2-4) in gliomas and meningiomas

Epidermal growth factor receptor family (EGFR, ErbB2-4) in gliomas and meningiomas
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DOI:
10.1007/s00401-004-0875-6
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发表时间:
2004-08-01
影响因子:
12.7
通讯作者:
Henriksson, R
Henriksson, R
中科院分区:
医学1区
文献类型:
--
作者:
Andersson, U;Guo, D;Henriksson, R

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表皮生长因子受体(EGFR,ErbB 1)的过表达与包括多形性胶质母细胞瘤在内的许多人类肿瘤类型的恶性潜能增强相关。然而,EGFR在脑膜瘤中表达的意义尚不清楚。关于EGFR家族其他成员ErbB 2 -4在脑肿瘤中的报道很少。在这项研究中,EGFR家族成员的表达进行了分析,这些受体在44个胶质瘤和26个脑膜瘤的临床重要性的各种参数。在胶质瘤中,定量实时逆转录(RT)-PCR显示EGFR mRNA在高级别胶质瘤中表达最高,而ErbB 2和ErbB 3 mRNA仅在少数高级别胶质瘤中检测到。相反,ErbB 4表达在低级别胶质瘤中最明显。免疫组化显示EGFR蛋白在高级别胶质瘤中的表达显著高于低级别胶质瘤(P=0.004)。ErbB 2蛋白表达主要见于高级别胶质瘤。ErbB 3蛋白在所有分析的胶质瘤中表达均较低。ErbB 4蛋白在低级别胶质瘤中的表达显著高于高级别胶质瘤(P=0.007)。在脑膜瘤中,实时定量RT-PCR显示EGFR、ErbB 2和ErbB 4 mRNA在大多数肿瘤中表达。ErbB 3仅在1例脑膜瘤中检出。免疫组化结果显示脑膜瘤中ErbB 2蛋白高表达。在星形细胞瘤和II级少突胶质细胞瘤中观察到一个有趣的现象,即EGFR蛋白高表达患者的总生存率显著降低(P=0.04)。与高级别胶质瘤相比,ErbB 4在低级别胶质瘤中的高表达可能表明ErbB 4可以抑制脑肿瘤的恶性转化,这与之前在其他肿瘤类型中的研究一致。
Overexpression of epidermal growth factor receptor (EGFR, ErbB1) correlates with enhanced malignant potential of many human tumor types including glioblastoma multiforme. The significance of EGFR expression in meningiomas is, however, unclear. Reports regarding the other EGFR family members, ErbB2-4, in brain tumors are sparse. In this study, the expression of the EGFR family members was analyzed in relation to various parameters for the clinical importance of these receptors in 44 gliomas and 26 meningiomas. In gliomas, quantitative real-time reverse transcription (RT)-PCR revealed the highest EGFR mRNA expression in high-grade gliomas, while ErbB2 and ErbB3 mRNA were detected only in a few high-grade gliomas. In contrast, ErbB4 expression was most pronounced in low-grade gliomas. Immunohistochemistry showed significantly higher EGFR protein expression in high-grade gliomas compared to low-grade gliomas (P=0.004). ErbB2 protein expression was mainly seen in high-grade gliomas. ErbB3 protein expression was low in all gliomas analyzed. ErbB4 protein expression was significantly higher in low-grade gliomas than in high-grade gliomas (P=0.007). In meningiomas, quantitative real-time RT-PCR revealed expression of EGFR, ErbB2, and ErbB4 mRNA in the majority of the tumors. ErbB3 was detected in only one of the meningiomas analyzed. Immunohistochemistry demonstrated high ErbB2 protein expression in meningiomas. An intriguing observation in astrocytomas and oligodendrogliomas grade II, was a significantly decreased overall survival for patients with high EGFR protein expression (P=0.04). The high ErbB4 expression in low-grade compared to high-grade gliomas might suggest that ErbB4 acts as a suppressor of malignant transformation in brain tumors, which is in line with previous studies in other tumor types.