Notch1胞内结构域在星形细胞肿瘤中的表达及其临床意义

Expression of Notch1 intracellular domain in astrocytic tumors and their clinical significance:an analysis based on 97 cases

目的探讨Notch1胞内结构域(intracellular Domain,ICD)在星形细胞肿瘤中的表达规律及其临床意义。方法收集大坪医院2009年1-6月间经手术切除的12例不同级别星形细胞肿瘤及2例瘤周正常脑组织新鲜标本,采用实时定量PCR方法检测Notch1ICD mRNA表达;收集85例有完整随访资料的星形细胞肿瘤存档标本,采用免疫组织化学技术检测Notch1ICD蛋白表达。结果 Notch1ICD在正常脑组织中低或不表达,肿瘤组织中Notch1ICD mRNA水平(4.65±3.04)显著高于正常脑组织(1.13±0.11)(P<0.01);高级别(WHOⅢ和Ⅳ级)星形细胞肿瘤Notch1ICD mRNA表达水平显著高于低级别星形细胞肿瘤(WHOⅡ级)[分别为(6.58±2.63)与(2.49±1.01),P<0.01]。免疫组化结果显示,相对于瘤周正常脑组织,各级星形细胞肿瘤Notch1ICD表达明显增强,并由单纯胞质表达向胞质胞核联合表达及单纯胞核表达过渡;Notch1ICD蛋白表达与组织学分级及患者的存活期有关,Notch1ICD高表达预示着较高的组织学分级和较短的存活时间。结论 Notch信号通路的激活是星形细胞肿瘤的常见事件,Notch1ICD的异常表达与肿瘤分级及患者预后关系密切,可能成为胶质瘤基因治疗的有用分子靶标之一。

Objective To explore the expression pattern of Notch1 intracellular domain（ICD）in astrocytic tumors and its clinical significance.MethodsNotch1 ICD mRNA was detected in 12 fresh-resected astrocytic tumors of various grades after pathological diagnosis and 2 normal cerebral tissues in Daping Hospital from January to Jane in 2009 by real-time quantitative PCR.Notch1 ICD protein was detected in 85 archived astrocytic tumor samples at different grades using immunohistochemical method.ResultsMild or low expression of Notch1 ICD mRNA was found in normal cerebral tissues.The expression level of Notch1 ICD mRNA in neoplastic tissues（4.65±3.04）were significantly higher than in normal tissues（1.13±0.11）（P0.01）.There was statistical significance of difference of Notch1 ICD mRNA expression between high-grade astrocytic tumors（grade Ⅲ and Ⅳ,n=7）and low-grade tumors（gradeⅡ,n=5）（6.58±2.63 vs 2.49±1.01,P〈0.01）.Immunohistochemical results revealed that obvious upregulation of Notch1 ICD protein was seen in neoplastic tissues,and transformation of protein localization from pure cytoplasmic staining,combined cytoplasmic and nuclear staining,to pure nuclear staining.The expression of Notch1 ICD protein was correlated with histological grade and patient＇s survival time.Higher expression of Notch1 ICD protein predicted higher malignant grade and shorter survival time.ConclusionActivation of Notch signaling is frequently found in astrocytic tumors.Aberrant expression of Notch1 ICD is correlated with tumor malignant grade and patient＇s survival,which implies that Notch1 might be one of useful target molecules for anti-glioma gene therapy.