Study Of MMP-2 And TIMP-1 Expression In Nephroblastoma And Clinical Significance

Objective:The matrix metalloproteinases (MM1Ps) are responsible for degradation of the extracellular matrix (ECM) in tumor invasion and metastasis. Among them, MMP-2 is found to be most important because it hydrolyzes the type IV collagen of the basement membrane (BM). Tissue inhibitor of matrix metalloproteinase-l (TIMP- 1) form complexes with MMPs, inhibit their enzymatic activity They are responsible for inhibition of tumor invasion and metastasis by blocking degradation of ECM. This study was carried out to detect the expression of MMP-2 and TIMP-1 in nephroblastoma and to investigate whether they have any association with nephroblastoma metastasis and clinical outcome.Methods:Inimunohistochemical staining technique (Streptavidin-peroxidose method) was used to detect the expression of MMP-2 and T1MP- 1 in paraffin sections of tumor tissues from 42 children with nepbroblastoma and of normal kidney tissues from 8 embryos. Average optical density (AOD) of MMP-2 positive immunoreactivity in vascular endothelium was assessed by image analyser. The percentage of tumor cells with positive immunoreactivity was use to assess the TIMP-l expression pattern. The correlation between MMIP-2, TIIvIP-l expression and clinicopathological parameters were analyzed.Results:MMP-2 staining was confined mostly to the stromal tissues. The expression of MMP-2 had no association with pathological type (P>O.05). Increased expression of MMP-2 had significant association with advanced clinical stages and tumor invasion and metastasis (NO.0 1). TIMP-l staining was confined mostly to the neoplastic cell cytoplasm. Decreased expression of TIMP- 1 had significant association with nephroblastoma invasion and metastasis (PO.05).Conclusions:MMP-2 may play an important role in nephroblastoma progressin and metastasis. MIvIP-2 expression is correlated with nephroblastoma invasion and metastasis and clinical stages. TIMP-l expression is inversely correlated with nephroblastoma invasion and metastasis. An early detection of MMP-2 and TIMIP-l expression pattern by immunohistochemistzy in nephroblastoma may provide prognostic informations in clinical practice.