Objective To study the expression and functional role of S phase kinase associated protein 2 (Skp2) in development of glioma. Methods Sixty surgically removed specimens of primary glioma and 4 normal brain specimens were obtained from the Department of Neurosurgery, Navy General Hospital of PLA, from June 2001 to June 2006. All the specimens were graded according to WHO Criteria as astrocytoma (grade II, n=20), anaplastic astrocytoma (grade ID, n=20) and glioblastoma (grade IV, n=20). Western blotting and immunohistochemistry were used to detect the expression of Skp2 in specimens of glioma of different grades and normal brain tissue. Results Western blotting demonstrated that the expression of Skp2 in normal brain tissue was significantly lower than that in glioma specimens, and the expression increased in degree along with the elevation of malignant grade. Immunohistochemical staining showed that the Skp2 positively expressed in both the normal brain tissues and gliomas. However, Skp2 was weakly positive and mainly found in the cytoplasm in normal brain tissue and low grade glioma (grade II ), while it was strongly positive and mainly observed in the nuclei in high grade glioma (grade IH and IV). Furthermore, the positive expression of Skp2 was also observed in vascular endothelial cells of glioma tissue, and the glioma cells with positive Skp2 were found to gather around the vessels in glioma specimens. Statistically analysis showed that the expression of Skp2 was significantly higher in high grade glioma tissues (grade 1H and IV) than in normal brain tissues and low grade glioma (grade II ) with significant difference (P<0.0l). Conclusions Along with the increase in malignancy of glioma, the expression of Skp2 was found increasing gradually, and it transferred from cytoplasm to nuclei. Skp2 positively expressed in both vascular endothelial cells of glioma tissue and the glioma cells around vessels in glioma specimens. The change in Skp2 expression might be closely related to an increase in malignancy of glioma, the formation of new vessels, and metastasis of tumor cells.%目的 探讨S期激酶相关蛋白2(Skp2)在胶质瘤中的表达情况及其功能意义.方法 收集海军总医院神经外科2001年6月-2006年6月手术切除的原发胶质瘤标本60例,根据WHO胶质瘤分类法(2000年),其中星形细胞瘤(WHOⅡ级)、间变性星形细胞瘤(WHOⅢ级)、胶质母细胞瘤(WHO Ⅳ级)各20例,另取4例正常脑组织作为对照.采用Western blotting及免疫组化法检测正常脑组织及不同恶性程度胶质瘤组织中Skp2的表达情况.结果 western blotting结果显示,正常脑组织中Skp2表达明显低于胶质瘤组织,且随着胶质瘤恶性程度的增高,Skp2蛋白表达逐渐增强.免疫组化染色显示,正常脑组织及胶质瘤组织中均有Skp2阳性表达,其中正常脑组织和WHOⅡ级胶质瘤中Skp2呈弱阳性,多位于胞质,WHOⅢ级和Ⅳ级胶质瘤中Skp2表达呈强阳性,阳性染色颗粒集中于细胞核.胶质瘤组织中的血管内皮细胞也有Skp2阳性染色,且在血管周围有Skp2阳性染色的肿瘤细胞聚集.统计学分析显示,Skp2在高度恶性胶质瘤组织(WHOⅢ级、Ⅳ级)中的表达明显高于正常脑组织和低度恶性的胶质瘤组织(WHOⅡ级),差异有统计学意义(P＜0.01).结论 随着胶质瘤的恶性进展,Skp2表达逐渐增强,且由细胞质转移至细胞核；在胶质瘤组织新生血管内皮细胞及血管周围肿瘤细胞中均有Skp2阳性表达.Skp2的表达变化可能与胶质瘤的恶性进展、新生血管的形成及肿瘤细胞的转移密切相关.
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