p16基因CpG岛甲基化与胶质瘤生物学特性的关系

目的：研究p16基因CpG岛甲基化与胶质瘤恶性程度分级及肿瘤细胞增殖活性的关系。方法：应用半巢式甲基化特异性多聚酶链反应（MSP）检测40例不同级别的胶质瘤组织标本中p16基因CpG岛甲基化状态。免疫组化SP法分析肿瘤组织p16蛋白和Ki-67抗原的表达情况。结果：肿瘤组织甲基化发生率为42.5%（17/40）,p16蛋白表达缺失率为72.5%（29/40）,其中55.2%（16/29）缺失与甲基化有关（P=0.0085）。甲基化发生率随胶质瘤恶性程度增加有增高趋势（χ2=11.4288,P=0.0007）。甲基化阳性者中Ki-67抗原增殖指数明显高于甲基化阴性者（P〈0.05）。结论：p16基因CpG岛甲基化导致该基因灭活是胶质细胞恶性增生的主要机制之一。

The relation between hypermethylation of the CpG island of p16 gene and the biological characteristics of brain glioma

Objective To study the relation between hypermethylation of the CpG island of p16 gene and the malignant grades of brain glioma and the proliferative activity of tumor cells.Method Methylation status of the CpG island of p16 gene was detected by methylation-specific PCR (MSP) in plasma and brain tumor specimens in 40 patients with gliomas in different grades. Immunohistochemical method (SP) was used to analyze the expression of the p16 and Ki-67 protein.Results Methylation of brain gliomas was found in 42.5% of all the specimens(17/40). Immunohistochemical analysis showed an absence of p16 protein in 72.5% of (29/40) brain gliomas, where hypermethylation was found in 55.2%(16/29), suggesting a highly significant (P=0.0085) correlation between hypermethylation of the gene and absence of p16 protein. The positive rate of methylation of p16 gene was significantly (P<0.05) related to the increase of malignant grades of brain glioams. The Ki-67 index increased significantly (P<0.05) in brain glioams methylated compared to those unmethylated.ConclusionThe p16 gene silencing caused by hypermethylation of CpG island is a major mechanism to promote tumor cells proliferation.