The Expression Of TIMP-1 And TIMP-2 In Gliomas

Objective Through detecting the expression and DNA mutations of tissue inhibitor of metalloproteinase-1 (TIMP-1) and tissue inhibitor of metalloproteinase-2 (TIMP-2) in human gliomas to study their heterogenous expression in gliomas and the reason of the heterogenous expression.Methods①The expression of TIMP-1 and TIMP-2 in 119 cases of gliomas were detected by immunohistochemical PV6000 method.②TIMP-1 gene mutations in exon3 and TIMP-2 gene mutations in exon2 were examined in these 119 specimens of gliamas using PCR-SSCP analyses, and the positive specimens were confirmed by DNA sequencing.③The immunohistochemical results were analyzed using the software of SPSS11.5 by means of. Chi-Square test,Rank sum test and Kendall's rank correlation analysis.Results①The expression rate(X~2=24.97, P＜0.01; X~2=44.03, P＜0.01) and intensity(u=567.5, P＜0.01; u=447.0, P＜0.01) of TIMP-1 and TIMP-2 in gliomas was higher than that of in non-tumor tissues. The result was of statistical significance.②The expression rate(u=622.50, P＜0.01; u=395.00, P＜0.01) and intensity(r=0.271, P＜0.01; r=0.319, P＜0.01) of TIMP-1 and TIMP-2 in astrocytomas had negative correlation with the differentiation degree.③TIMP-1 and TIMP-2 expressed in all blood vessels of the non-tumor brain tissue and gliomas. But their expression intensity were higher in blood vessels of gliomas. The result was of statistical significance (u-292.5, P＜0.01; u=409.5, P＜0.01).④PCR products were proved to be the aimed size through agarose gel electrophoresis.⑤PCR-SSCP and silver staining displayed that TIMP-1 exon3 and TIMP-2 exon2 in all the 119 gliomas had no mutations.Conclusions TIMP-1 and TIMP-2 expressed negatively or poorly in none-tumor brain, but intensively in gliomas; The difference was significant. The expression level of TIMP-1 and TIMP-2 was positively correlated with the malignant degree of astrocytomas; These two may serve as markers to judge the clinical prognosis of astrocytomas. TIMP-1 and TIMP-2 expressed much more in gliomas and were positively correlated with malignent degrees of gliomas; These phenomenon result from a mechanism of compensation. We had not detected any proof to indicate correlation of the gene mutation and the higher expression of TIMP-1 and TIMP-2. TIMP-1 and TIMP-2 were closely related with progression and heterogeneity of brain gliomas. TIMP-1 and TIMP-2 expressed in all vascular endothelial cells of small vessel, and expressed much more in immature and new vessels. These two might be closely related with angiogenesis of normal brain and angiopoiesis of brain gliomas.