尿激酶及其受体在人脑胶质瘤中的表达

EXPRESSION OF UROKINASE AND UROKINASE RECEPTOR IN HUMAN GLIOMAS

目的研究尿激酶（ｕＰＡ）、尿激酶受体（ｕＰＡＲ）在人脑胶质瘤中的表达特征，评估其在胶质瘤恶性生长方式中的作用。方法选取５７例不同恶性程度的星形细胞瘤、１３例良性脑膜瘤和１０例正常脑组织，分别以抗ｕＰＡ单克隆抗体和抗ｕＰＡＲ多克隆抗体用ＡＢＣ法进行免疫组织化学染色和半定量分析。结果ｕＰＡ、ｕＰＡＲ的表达程度与胶质瘤的恶性程度有关，胶质瘤恶性程度越高，表达程度越高；良性脑膜瘤的表达程度较低；正常脑组织则未见ｕＰＡ、ｕＰＡＲ的表达。ｕＰＡ染色除见于肿瘤细胞、血管内皮细胞外，还见于少数胶质增生带的正常胶质细胞和神经元。在肿瘤细胞增殖密集区域，ｕＰＡ阳性的肿瘤细胞比例较低，而在肿瘤细胞生长较稀疏、肿瘤血管增殖旺盛的区域阳性细胞比例较高。ｕＰＡＲ的染色定位于肿瘤细胞和血管内皮细胞。结论ｕＰＡ和ｕＰＡＲ的共同表达是浸润性生长的胶质瘤的特征之一。其表达程度可作为判断星形细胞瘤浸润性的重要参考指标。在人体内，表达ｕＰＡ的细胞种类是较多的。ｕＰＡ、ｕＰＡＲ的表达对胶质瘤的浸润和血管发生可能起着重要作用。

PURPOSE To study the patterns of the expression of urokinase(uPA), urokinase receptor(uPAR) in human gliomas. METHODS The immunohistochemical localization of uPA and uPAR was evaluated by using the avidin-biotin immunoperoxidase technique. Studies were performed in 80 surgical excised specimens, including 57 astrocytomas, 13 benign meningiomas and normal brain tissue of 10 cases. The immunohistochemical staining results were densitometrically semiquantitatived. RESULTS The intensity of the immunoreaction correlated with biological malignancy of astrocytoma. A semiquantitative analysis of immunohistochemical results showed that uPA and uPAR were overexpressed in Ⅲ～ Ⅳ grade astrocytomas in comparison with Ⅰ～Ⅱ grade astrocytomas or meningiomas, and they were undetectable in normal brain tissue. The staining for uPA was mainly localized on tumor cells and vascular endothelial cells, but was also seen on a few normal glial cells and neurons adjacent to glioma tissue. The uPA staining was hetrogeneously distributed with preferential localization in the areas of vascular proliferation. The astrocytoma cells in denser proliferated areas showed minor uPA positivity. The staining for uPAR was localized on astrocytoma cells and endothelial cells. CONCLUSIONS We showed that overexpression of uPA and uPAR is a constant feature of invasive malignant astrocytomas in vivo. The cellular source of uPA was not only from astrocytoma cells and endothelial cells, but also from some other cells, maybe include normal glial cells and neurons. The combined increased expressin of uPA and its cellular receptor, uPAR, may account for the activasion of the proteolytic system which occours in invasion and angiogenesis of astrocytoma.