血管内皮生长因子在脑复发胶质瘤中的表达

背景:脑胶质瘤病灶介质中富含新生血管,血管内皮生长因子表达不同可能与其病理表现和复发存在一定的相关性。目的:分析血管内皮生长因子在复发脑胶质瘤中表达的特征。设计:对照实验。单位:四川大学华西医院神经外科。对象:从华西医院1996-06/2001-06手术切除且病理证实为脑胶质瘤143例石蜡标本中,收集临床资料完整且相同的个体复发前、后脑胶质瘤标本44例(22对)。取首次手术及第1次复发手术标本。其中Ker-nohan评分Ⅰ级8例;Ⅱ级10例;Ⅲ级14例;Ⅳ级12例。分为初发和复发2组,每组22例。方法:采用免疫组织化学SP法,一抗羊抗人血管内皮生长因子IgG(单抗)、二抗兔抗羊IgG,工作度1:50,阴性对照为磷酸盐缓冲液置换一抗染色。检测44例复发前、后的脑胶质瘤病理组织中血管内皮生长因子蛋白表达水平,结合病理分级作对照分析。①胞浆内呈棕黄色颗粒为阳性信号。②在MPIAS-500型多媒体彩色病理图文分析系统上,对肿瘤细胞进行表达强度PU值(阳性单位)和细胞数测定。③PU值95%临界值,分别计数阳性细胞率。④常规苏木精-伊红染色Kernohan病理分级。主要观察指标:①脑胶质瘤复发前、后标本血管内皮生长因子表达强度PU值。②脑胶质瘤复发前、后组病理分级。结果:①脑胶质瘤血管内皮生长因子表达强度PU值:初发组为21.9273±6.607,复发组为33.0545±6.684。②病理分级:初发Ⅰ级8例,复发Ⅱ级2例、Ⅲ级5例、Ⅳ级1例;初发Ⅱ级6例,复发Ⅱ级2例、Ⅲ级1例、Ⅳ级3例;初发Ⅲ级6例,复发Ⅲ级2例、Ⅳ级4例;初发Ⅳ级2例,复发Ⅳ级2例。③脑胶质瘤复发前、后标本血管内皮生长因子蛋白表达PU值和肿瘤复发前、后病理分级各自对比检验差异均有显著性(P<0.05)。结论:血管内皮生长因子表达强度在脑胶质瘤复发较初发时增加明显,复发肿瘤恶化趋势与血管内皮生长因子的高表达在胶质瘤的复发中呈一致性。

Expression of vascular endothelial growth factor in recurrent brain glioma

BACKGROUND: Neuroglioma is easy to recur, the focus of infection in which is rich in new vessels. Different expression of vascular endothelial growth factor (VEGF) may be related with the pathologic changes and recurrence of tumor.OBJECTIVE: To analyze the characteristics of VEGF expression in recurrent brain glioma.DESIGN: Control test.SETTLNG: Department of Neurosurgery, West China Hospital of Sichuan University.PARTICIPANTS: Forty-four (22 pairs) samples of neurogliocytoma before and after the recurrence with complete clinical data were collected from143 paraffin embedded samples, which were obtained from the operation between June 1996 and June 2001 in West China Hospital and pathologically proved to be brain gliomas. Samples were collected separately from the first operation and first recurrence, in which 8 cases belonged to grade Ⅰ of Kernohan scale, 10 were grade Ⅱ , 14 were grade Ⅲ and 12 were grade Ⅳ. The enrolled samples were divided into two groups: primary group and recurrent group with 22 cases in each group.METHODS: The immunohistochemiscal method was adopted. First antibody was goat-anti-human VEGF (mono-antibody), and second antibody was rabbit-anti-goat with the working concentration of 1:50. The phosphate buffered solution (PBS) was taken as negative control for staining instead of first antibody. The protein expression of VEGF in brain gliomas of 44 cases before and after the recurrence were detected and the cross-check analysis was conducted by combing with pathologic grades. ① The buff grains in intracytoplasm were positive signals. ②MPLAS-500 media mix chromatic pathologic imaging and literal analytical system were used to detect the PU (positive unit) value and number of tumor cells.③95% were the critical value of PU value, and the positive cell rates were calculated respectively. ④Routine hematoxylin-eosin stain was used for pathologic grades (Kernohan). MAIN OUTCOME MEASURES: ① PU value and the intensity of VEGF expression in brain glioma samples before and after the recurrence. ②The pathologic grades of brain gliomas before and after the recurrence. RESULTS: ①The expression of VEGF in primary and recurrent groups of brain glioma: the primary group was 21.927 3±6.607 and the recurrent group was 33.054 5±6.684. ② Pathologic grades: In 8 cases of primary grade Ⅰ gliomas, there were 2 cases of grade Ⅱ in recurrence, 5 cases of grade Ⅲ in recurrence, 1 case of grade Ⅳ in recurrence. In 6 cases of primary grade Ⅱ gliomas, there were 2 cases of grade Ⅱ in recurrence, 1case of grade Ⅲ in recurrence, 3 cases of grade Ⅳ in recurrence. In 6eases of primary grade Ⅲ .gliomas, 2 cases of grade Ⅲ in recurrence, 4cases of grade Ⅳ in recurrence. In 2 cases of primary grade Ⅳ gliomas,there were 2 cases of grade Ⅳ in recurrence. ③ Differences in PU value of VEGF protein expressions and pathologic grades of brain glioma samples before and after recurrence in self-compared detection were remarkable (P＜0.05).CONCLUSION: The expression of VEGF in recurrent glioma is higher than primary glioma, and there is a worsening tendency in recurrent tumor and the high-expression of VEGF in glioma plays an important role in the recurrence.