胶质瘤中EGFR扩增、过表达及其与肿瘤增殖关系的研究

The relationships of the amplification and gene expression of EGFR with tumor proliferating activity

目的探讨表皮生长因子受体(EGFR)在胶质瘤中扩增、过表达及其在肿瘤增殖中的作用机制。方法应用SP免疫组化法、RT-PCR、Southern印迹法检测6例正常脑组织、50例不同级别胶质瘤及2个体外胶质瘤细胞系中在EGFR蛋白水平、mRNA水平、DNA水平的表达及扩增情况,以及与肿瘤增殖活性的相关性。结果不同级别的胶质瘤中,表达与扩增程度不同,Ⅱ级与Ⅲ、Ⅳ级肿瘤之间比较具有显著性差异;EGFR过表达与Ki-67在胶质瘤中的表达呈正相关,而EGFR过表达与扩增并不一致。结论EGFR过表达与胶质瘤的增殖活性增高有密切相关性,推测EGFR过表达是肿瘤进展中的早期事件而非进展期事件。

Objective To study the distribution, expression and amplification of proto-oncogenes EGFR in human gliomas in China. Methods The gene expression of EGFR in 50 human gliomas, 2 malignant human glioma cell lines and 6 normal brain tissues were studied by immunohistochemical staining, Southern blot analysis and RT-PCR. The relationship between their expression was analysed, and their expression level correlated with glioma and proliferation activity was also studied, Results Immunohistochemical study showed EGFR expression rate was 70,59% （24/34） in high-grade gliomas, where it was 50% （8/16） in low grade gliomas. Both 2 malignant human cell lines expressed EGFR, and 6 normal brain samples had no EGFR protein expression. EGFR expression was significantly increased in ascending order from low to high grade gliomas, The results of RT-PCR analysis using a cDNA probe were coincident with that of immunohistochemical staining. EGFR gene amplification only existed in l case of human low grade gliomas（l/16） and one human malignant glioma cell line （1/2）, but in 12 cases in human high grade gliomas（12/34）. Comparing the immunostaining pattern of EGFR protein with the amplification of EGFR, we found a discrepancy between them. 14 cases manifested with EGFR gene overexpression without gene amplification. Conclusion EGFR over-expression is often observed in low grade glioma, which differs from the reports from most other Europe country and America, and there is a significant correlation with glioma grades. EGFR gene signaling pathways was associated with the proliferation activity in human gliomas. EGFR gene may play an important role in the malignant progression in gliomas.