EGFR过表达和基因扩增状态差异与胶质瘤临床病理和细胞凋亡关系研究

The relationship of the amplification and gene expression of EGFR with the clinical pathology of glioma and tumor apoptosis activit

目的探讨人类表皮生长因子受体(EGFR)在胶质瘤中的表达和基因扩增状态,并分析其与肿瘤细胞凋亡的关系。方法采用Envision免疫组化二步法、westernblot和荧光原位杂交法(FISH)检测10例正常脑组织、60例不同级别原发性胶质瘤和25例继发性胶质母细胞瘤组织中EGFR蛋白水平和基因扩增状态,并分析其与肿瘤凋亡蛋白P53的相关性。结果在不同级别的原发性胶质瘤组织中,EGFR的阳性表达与扩增程度不同,Ⅰ～Ⅱ级组与Ⅲ～Ⅳ级组间比较具有统计学差异(P<0.05);原发性胶质瘤中EGFR免疫组化阳性率和基因扩增率分别为85%和40%,显著高于继发性胶质母细胞瘤(28%和28%),差异均具有统计学意义(P均<0.05);EGFR过表达与基因扩增状态并不一致,在有EGFR扩增的原发性胶质母细胞瘤中均有EGFR过表达,在EGFR过表达的肿瘤中仅有31.03%EGFR扩增;在胶质瘤中EGFR阳性表达与P53呈正相关(r=14.22,P=0.001)。结论 EGFR在不同级别胶质瘤中差异性过表达和扩增,且与肿瘤细胞凋亡相关,其基因扩增状态在原发性和继发性胶质母细胞瘤中存在差异,EGFR可作为胶质母细胞瘤治疗的一个重要靶点。

Objective To investigate the relationship of the amplification and gene expression of Epidermal growth factor receptor （EGFR） with the clinical pathology of glioma and tumor apoptosis activity. Methods The amplification and gene expression of EGFR in 10 normal brain tissue , 60 primary gliomas of different degrees and 25 Secondary glioma were studied by immunohistochemical staining, western blot analysis and filter in situ hybridization （FISH）. The relationship between expression level of EGFR and apoptosis activity in glioma （by detecting the expression of 1953, a protein associated with apotosis ） was studied. Results The amplification and gene expression of EGFR were different from glioma degree. EGFR expression was significantly increased in ascending order from low to high grade glioma（ P 〈 O. 05 ）. The rate of EGFR-immunohistochemical staining （ EGFR-IHC ） and EGFR-FISH was 85% and 40% in primary glioma, and it was 28% and 28% in secondary gliomas （ P 〈 0.05 ） . The results of FISH analysis of EGFR expression were not coincident with that of immunohistochemical staining. The primary glioblastoma cases with EGFR gene amplification were also with EGFR overexpression but only 31. 03% EGFR gene amplification in the cases of EGFR overexpression. It was positively correlated between expression of EGFR and P53 （ r = 14. 22, P = 0. 001 ）. Conclusions Expression and amplification level of EGFR has significantly different in different degree glioma, and it related to tumor cell apoptosis. The state of EGFR gene amplification was different in primary and secondary glioblastoma. EGFR may be a treatment target in glioblastoma treatment in future.