中国人脑星形胶质细胞瘤中表皮生长因子受体的表达及其靶向治疗

背景越来越多恶性脑胶质瘤存在的基因缺陷被发现,恶性脑胶质瘤的基因治疗逐渐成为热点,胶质瘤的治疗可以靶向于脑胶质瘤的基因缺陷.目的研究中国人脑星形胶质细胞瘤中表皮生长因子受体(epidermalgrowthfactorreceptor,EGFR)的表达,并探讨其临床意义.设计以金标准为依据的诊断性试验的病例观察性研究.地点、对象和干预人脑星形胶质细胞瘤新鲜手术标本37例,其中男22例,女15例,年龄11～69岁,平均37岁,均来自于1998/2000长征医院手术病例.样本包含术中所切除肿瘤组织及配对瘤周组织,按照Kernohan病理分级,分为低级别组(Ⅰ～Ⅱ级,12例)和高级别组(Ⅲ～Ⅳ级,25例).人脑胶质瘤细胞株U87MG,U251MG,大鼠脑胶质瘤细胞株C6.应用免疫组化方法(Evision-HRP法)检测人脑星形胶质瘤标本(含配对瘤周组织)和体外培养的多株人和大鼠胶质瘤细胞系的EGFR表达.主要观察指标EGFR在人星形细胞瘤、脑胶质瘤细胞株中的表达;EGFR表达与肿瘤病理分极的相关性.结果人脑星形胶质瘤组织EGFR阳性率为70%(26/37),明显高于瘤周组织(32%,12/37),差异有显著性意义(x2=10.602,P＜0.01).Ⅲ～Ⅳ级肿瘤EGFR阳性率为84%(21/25),Ⅰ～Ⅱ级为42%(5/12),高级别组肿瘤EGFR表达水平显著低于低级别组,差异有显著性意义.(x2=6.955,P＜0.01),体外实验显示不同来源细胞系间的EGFR表达率差异存在显著性意义.结论中国人脑星形胶质瘤存在EGFR的过度表达,提示EGFR可作为恶性脑胶质瘤细胞的标志物.为基因治疗提供了适宜的靶向,为研究EGFR介导的脑胶质瘤靶向性基因治疗建立基础.

Expression ofepidermal growth factor receptor of brain astrocytoma in Chinese and target treatment

BACKGROUND: With more and more gene defects of malignant brain gliomas being found, gene therapy has been popular for treating malignant brain gliomas by targeting specific gene defect.OBJECTIVE: To study the expression of epidermal growth factor receptor(EGFR) and discuss its clinical significance.DESIGN: Case observational research of diagnostic test on the basis of gold standard.SETTINGS and PARTICIPANTS: Thirty-seven fresh surgical specimens of brain astrocytoma from 22 males and 15 females in Changzheng Hospital during 1998 to 2000 were chosen, patients aged from 11 to 69 years old, with an average age of 37 years old.INTERVENTION: The specimens of brain astrocytoma which included surrounding tissues of tumors and the EGFR expressions of glioma cell lines in human and rats by culture in vitro were detected by Evision-HRP method. The specimens included tumor and pairing surrounding tissues which were graded into low grade group(level Ⅰ - Ⅱ, 12 cases) and high grade group(level Ⅲ -Ⅳ, 25 cases). Human brain glioma cell strains were U87MG, U251MG and rats brain glioma cell strain was c6.MAIN OUTCOME MEASURES: Expressions of EGFR in human astrocytoma and brain glioma cell strains; correlation between EGFR expressions and grading of tumor pathology.RESULTS: The positive rate of EGFR in human brain astrocytoma was 70%(26/37) which was higher than that in surrounding tissue of tumor(32%,12/37) . There was significant difference between these two rates(X2 =10. 602, P ＜ 0.01). The positive rate of EGFR in level Ⅲ - Ⅳ was 42%(5 / 12). The expression of EGFR in high grade group was much lower than that in low grade group, there was significant difference between two groups(X2 =6. 955, P ＜ 0.01 ). The in vitro experiment indicated that there was significant difference among expressions of EGFR in cell lines from different sources.CONCLUSION: EGFR can be regarded as marker of malignant braingliomas. It provides suitable target for gene therapy and establishes research basis for target gene treatment of brain gliomas conducted by EGFR.