胶质瘤浸润组织中MMP-2、MMP-9、VEGF、Flk-1和P16的表达及其临床意义

Expressions of MMP-2,MMP-9,VEGF,Flk-1 and P16 in glioma invasive tissues and their clinical significances

目的:检测人脑胶质瘤浸润组织中基质金属蛋白酶2(MMP-2)、基质金属蛋白酶9(MMP-9)、血管内皮生长因子(VEGF)、血管内皮生长因子受体Flk-1和多种肿瘤抑制基因1(multiple tumor suppressor 1,P16)的表达,阐述其与胶质瘤浸润的相关性。方法:用原位杂交和免疫组织化学方法检测33例胶质瘤浸润组织中MMP-2、MMP-9、VEGF、Flk-1和P16的表达,并比较不同分组胶质瘤间表达率及P16的缺失率。结果:在Ⅰ-Ⅱ级与Ⅲ-Ⅳ级胶质瘤的浸润组织中,MMP-2和MMP-9的阳性表达率分别为20.00%、61.11%和13.33%、55.56%(P<0.01);VEGF和Flk-1阳性表达率分别为26.67%、66.67%和20.00%、72.22%(P<0.01);P16缺失率分别为13.33%和77.78%,两者之间比较差异有统计学意义(P<0.01)。结论:基质金属蛋白酶降解构成血脑屏障的基底膜和血管内皮细胞的过度增殖是胶质瘤浸润发生的必要条件。P16的缺失反映了恶性胶质瘤浸润组织具有增殖性生物学行为。

Objective To detect the expressions of the matrix metalloproteinase 2（MMP-2） matrix metalloproteinase 9（MMP-9） vascular endothelial growth factor（VEGF）,Flms like tyrosine kinase（Flk-1） and multiple tumor suppressor 1（P16） in human glioma invasive tissues,and to elaborate the correlation of the MMP-2,MMP-9,VEGF,Flk-1 and P16 with the glioma invasion.Methods The expressions of MMP-2,MMP-9,VEGF,Flk-1 and P16 were detected through in situ hybridization and immunohistochemistry in 33 cases of glioma invasive tissues.Results The positive rates of MMP-2 and MMP-9 in Ⅰ-Ⅱ grade and Ⅲ-Ⅳgrade glioma invasive tissues were 20.00%,61.11% and 13.33%,55.56%.The positive rates of VEGF and Flk-1 were 26.67%,66.67%and 20.00%,72.22%（P〈0.01）,respecttively;the P16 deletion frequencies were 13.33% and 77.78%,there was significant difference（P〈0.01）.Conclusion The necessary condition in occurrence of glioma invision is the basilar membrane degraded by the matrix metalloproteinases and the proliferative activity of vascular endothelial cells.The descended expression rate for P16 reflects the biological behavior of glioma invasive tissue