Notch1胞内结构域在星形细胞肿瘤中的表达及其临床意义 杨东虹.docVIP

Notch1胞内结构域在星形细胞肿瘤中的表达及其临床意义 杨东虹，唐文渊，徐伦山，周 椿，肖华亮，许民辉 （邮政编码、城市、单位（具体到科室）、相对应的英文翻译） [摘要 目的 探讨Notch1胞内结构域（ICD）在星形细胞肿瘤中的表达规律及其临床意义。方法 收集不同级别星形细胞肿瘤及瘤周正常脑组织新鲜标本，采用实时定量PCR方法检测Notch1 ICD 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Notch1 ICD蛋白表达。结果 Notch1 ICD在正常脑组织中低或不表达，肿瘤组织中Notch1 ICD mRNA水平显著高于正常脑组织；高级别（WHOⅢ和Ⅳ级）星形细胞肿瘤Notch1 ICD mRNA表达水平显著高于低级别组（WHOⅡ级）。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Notch1 ICD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；Notch1 ICD蛋白表达与组织学分级及患者的存活期密切相关，NICD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，Notch1 ICD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。关键词］脑肿瘤，星形细胞；Notch；逆转录聚合酶链式反应；免疫组织化学 Expression of Notch1 intracellular domain in astrocytic tumors and their clinical significance YANG Dong-hong，XU Lun-shan，XIAO Hua-liang，ZHOU Chun，XU Min-hui， TANG Wen-yuanDepartment of Neurosurgery，First Affiliated Hospital，Chongqing Medical University，Chongqing 400042，China [Abstract] Objective To explore the expression features of Notch1 intracellular domain（ICD）in astrocytic tumors and its clinical significance. Methods Notch1 ICD mRNA was detected in 12 fresh-resected astrocytic tumors and 2 normal cerebral tissues by real-time quantitative PCR. Notch1 ICD protein was detected in 85 archivedastrocytic tumors using immunohistochemical method. Results low expression of Notch1 ICD mRNA was found in normal cerebral tissues. The expression level of Notch1 ICD mRNA in neoplastic tissues were significantly higher than in normal tissues(P＜0.01). There was statistical significance of difference of Notch1 ICD mRNA expression between high-grade astrocytic tumors （gradeⅢand Ⅳ）and low-grade tumors（gradeⅡ）(P＜0.01). Immunohistochemical results revealed obvious upregulation of Notch1 ICD protein 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 correlated with histological grade and patient’s survival time. Higher expression of Notch1 IC