突变型异柠檬酸盐脱氢酶1(IDH1)水平与人脑胶质瘤细胞增殖和血管增生正相关

The expression of IDH1( R132H) is positively correlated with cell proliferation and angiogenesis in glioma samples

目的研究人胶质瘤中异柠檬酸盐脱氢酶1突变体(IDH1R132H)表达水平与肿瘤细胞增殖活性和血管形成之间的关系。方法采用测序法和免疫组织化学染色法检测IDH1突变情况和IDH1(R132H)表达水平,采用免疫组织化学染色法分析胶质瘤Ki-67标记指数,采用CD34免疫组织化学染色分析人胶质瘤组织中的血管数量,通过统计学方法,分析胶质瘤中IDH1(R132H)表达水平与肿瘤Ki-67标记指数和血管数量的相关性。结果 IDH1在Ⅱ级、Ⅲ级胶质瘤及继发性胶质母细胞瘤中突变率较高,且IDH1(R132H)表达水平与胶质瘤Ki-67和微血管密度存在明显的正相关。结论 IDH1在Ⅱ、Ⅲ级胶质瘤和继发胶质母细胞瘤中表达水平高,且突变型IDH1(R132H)的表达水平可能在胶质瘤的增殖和血管形成中发挥重要作用。

Objective To explore the correlations of the expression of mutant isocitrate dehydrogenase（ IDH1）（ R132H）protein with angiogenesis and cell proliferation in glioma. Methods We performed polymerase chain reaction-based IDH gene mutation screening in 385 glioma samples,and the subcellular localization and expression levels of IDH1（ R132H） was examined by immunohistochemistry（ IHC）. Ki-67 labeling index was introduced to determine the proliferation of glioma cells,and the microvessel density was measured through CD34 staining. Statistical analyses were performed to show the correlations of IDH1 mutation with cell proliferation and microvessel density. Results The mutant rates of IDH1 were about 50%-60% in grade Ⅱ-Ⅲ gliomas and secondary glioblastomas,which were significantly higher than those in pilocytic astrocytoma（ gradeⅠ）and primary glioblastoma（ grade Ⅳ）. Moreover,the level of IDH1（ R132H） protein was positively correlated with Ki-67 labeling index and microvessel density. Conclusion IDH mutation was common in grade Ⅱ-Ⅲ glioma and secondary glioblastoma,and the mutant IDH1（ R132H） might play a critical role in the cell proliferation and angiogenesis of glioma.