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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(WHOⅣ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。
Objective To investigate the expression of S-phase kinase-related protein 2 (Skp2) in gliomas and its functional significance. Methods Sixty patients with primary glioma surgically resected from June 2001 to June 2006 were collected from the Department of Neurosurgery, Navy General Hospital. According to WHO classification of glioma (2000), including astrocytoma (WHO grade Ⅱ) Anaplastic astrocytoma (WHO Ⅲ grade), glioblastoma (WHO Ⅳ grade) of 20 cases, another 4 cases of normal brain tissue as a control. Western blotting and immunohistochemistry were used to detect the expression of Skp2 in normal brain tissue and different malignant gliomas. Results Western blotting showed that Skp2 expression in normal brain tissue was significantly lower than that in glioma tissue, and Skp2 protein expression gradually increased with the increase of malignant degree of glioma. Immunohistochemical staining showed Skp2 positive expression in both normal brain tissue and glioma tissues, of which Skp2 was weakly positive in normal brain tissue and WHO grade II gliomas, mostly in cytoplasm, WHO grade III and IV gliomas Skp2 expression was strongly positive, positive staining particles concentrated in the nucleus. Vascular endothelial cells in glioma tissue also have Skp2-positive staining, and there are Skp2-positive staining of tumor cells around the blood vessels. Statistical analysis showed that the expression of Skp2 in high grade glioma tissue (WHO grade Ⅲ, grade Ⅳ) was significantly higher than that in normal brain tissue and low grade glioma (WHO grade Ⅱ) (P <0.05), the difference was statistically significant (P <0.01). Conclusion With the malignant progression of glioma, the expression of Skp2 gradually increases and translocates from the cytoplasm to the nucleus. Skp2 expression is also observed in both glioma and neovascular tumor cells. Skp2 expression may be related to the malignant progression of gliomas, the formation of new blood vessels and the metastasis of tumor cells.