Zhen Hai-Ning, Zhang Xiang, Hu Pei-Zhen, Yang Tong-Tao, Fei Zhou, Zhang Jian-Ning, Fu Luo-An, He Xiao-Sheng, Ma Fu-Cheng, Wang Xi-Ling
Institute of Neurosurgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, The People's Republic of China.
Cancer. 2005 Dec 15;104(12):2775-83. doi: 10.1002/cncr.21490.
An unbalance of cell proliferation and cell apoptosis is an important mechanism in carcinogenesis, and angiogenesis also plays a crucial role in tumorigenesis. Recently, survivin has been identified as an important member of the inhibitor of apoptosis protein (IAP) family. Although it has been shown that survivin is highly expressed in gliomas, and is associated with tumorigenesis, progression, and poor prognosis of gliomas, as yet the relation of survivin expression with proliferation, apoptosis, and angiogenesis of gliomas it is still unclear.
Eighty-three cases of brain glioma were chosen and protein expressions of survivin and proliferating cell nuclear antigen (PCNA) in glioma cells and Factor VIII-related antigen (FVIII-RAg) in vascular endothelial cells were investigated by immunohistochemistry. Apoptotic cells of brain glioma were screened by TdT-mediated dUTP nick end-labeling (TUNEL), and survivin immunoreactivity score (IRS), proliferative index (PI), apoptotic index (AI), overall daily growth (ODG), and microvessel density (MVD) in brain gliomas were measured.
The survivin IRS, PI, AI, ODG, and MVD of brain gliomas were 3.75 +/- 3.89, 28.39 +/- 19.49%, 1.00 +/- 0.80%, 12.19 +/- 10.21%, and 62.75 +/- 31.50, respectively, and all of them increased markedly with an increase in the pathologic grade of brain gliomas (P < 0.001 for all). PI, ODG, and MVD in the survivin-positive group were significantly higher than those in the survivin-negative group (P < 0.001 for all). PI, ODG, and MVD were positively correlated with survivin IRS (P < 0.001 for all). Although there was no significant difference between AI in the survivin-positive group or in the survivin-negative group (P = 0.108), AI was inversely correlated with survivin IRS (P = 0.005).
Survivin is overexpressed in brain gliomas, which may play an important role in malignant proliferation, antiapoptosis, and angiogenesis of brain gliomas.
细胞增殖与细胞凋亡失衡是肿瘤发生的重要机制,血管生成在肿瘤发生过程中也起着关键作用。最近,生存素被鉴定为凋亡抑制蛋白(IAP)家族的重要成员。尽管已表明生存素在胶质瘤中高表达,并与胶质瘤的发生、发展及不良预后相关,但生存素表达与胶质瘤增殖、凋亡及血管生成之间的关系仍不清楚。
选取83例脑胶质瘤病例,采用免疫组织化学法检测胶质瘤细胞中生存素和增殖细胞核抗原(PCNA)的蛋白表达以及血管内皮细胞中因子VIII相关抗原(FVIII-RAg)的表达。采用TdT介导的dUTP缺口末端标记法(TUNEL)筛选脑胶质瘤凋亡细胞,并检测脑胶质瘤中生存素免疫反应评分(IRS)、增殖指数(PI)、凋亡指数(AI)、总体日生长率(ODG)和微血管密度(MVD)。
脑胶质瘤的生存素IRS、PI、AI、ODG和MVD分别为3.75±3.89、28.39±19.49%、1.00±0.80%、12.19±10.21%和62.75±31.50,且均随脑胶质瘤病理分级的增加而显著升高(均P<0.001)。生存素阳性组的PI、ODG和MVD显著高于生存素阴性组(均P<0.001)。PI、ODG和MVD与生存素IRS呈正相关(均P<0.001)。尽管生存素阳性组与生存素阴性组的AI无显著差异(P=0.108),但AI与生存素IRS呈负相关(P=0.005)。
生存素在脑胶质瘤中过表达,可能在脑胶质瘤的恶性增殖、抗凋亡及血管生成中起重要作用。