骨巨细胞瘤基质金属蛋白酶系统的表达及其与复发的关系

Relationship between Expression of Matrix Metalloproteinases（MMPs） System and Recurrence of Human Giant Cell Tumor of Bone

目的:研究骨巨细胞瘤组织中基质金属蛋白酶-2和基质金属蛋白酶-9(matrixmetalloproteinaseMMP2,MMP9)及其特异性抑制剂金属蛋白酶组织抑制物-1和金属蛋白酶组织抑制物-2(tissueinhibitorsofmetalloproteinaseTIMP1和TIMP2)和尿激酶型纤溶蛋白酶原激活物(urokinasetypeplasminogenactivatoruPA)的表达与肿瘤复发的关系。方法:用免疫组化法和原位杂交法检测45例骨巨细胞瘤组织中MMP2、MMP9、TIMP1、TIMP2和uPA蛋白和RNA的表达,计算MMP2/TIMP2和MMP9/TIMP1的比值,对比肿瘤复发组和非复发组的差异。结果:骨巨细胞瘤组织有高水平的MMP2、MMP9、TIMP1、TIMP2和uPA表达,但与肿瘤的形态分级无关。复发组MMP2、MMP9和MMP2/TIMP2、MMP9/TIMP1比值以及uPA表达均比非复发组明显增高。高水平MMP2、MMP9、MMP2/TIMP2、MMP9/TIMP1表达的病例复发时间较早,复发风险较高。结论:骨巨细胞瘤的复发与基质金属蛋白酶和酶激活物表达增高,酶抑制剂表达减低相关。

Objective：To investigate the relationship between ex pression of MMP－２，MMP－９，their special inhibitors TIMP－１，TIMP－２，and u PA and recurren ce of human giant cell tumor of bone．Methods ：Expression of MM P－２，MMP－９，TIMP－１，TIMP－２，and uPA were detecte d by immunohistochemist ry and in sit u hybridization in ４５patients with g iant cell tumor of bone．Th e ratios of MMP－２／TI MP－２and MMP－９／TIMP－１were calculated and used as a n indicator．Results：Over－expression of MMP－２，MMP－９，TI MP－１，TIMP－２ ，and uPA was found in gia nt cell tumors of bone．However，there was no relatio nship between the enzy me expressions and histologic gradi ngs of the tumor．The expression levels of MMP－２，MMP－９，uPA and ratios of MMP－２／TIMP－２and M MP－９／TIMP－１were signi ficantly higher in recurrence group than that of non －recurrence group．T he tumor in the cases with higher leve l of MMP－２，MMP－ ９，MMP－２／TIMP－２，and MMP－９／TIMP－１recurred earlier，and had a higher r isk of recurrence．Conclusion：The recurrence of giant cell tumor of bone is cor related with high express ion of MMP－２，MMP－９，uPA and high ratios of MMP９ ／TIMP１，MMP２／TIMP２．