Expression Of β-catenin,MMP-7 And E-cadherin In Wnt Signaling Pathway During The Oncogenesis And Invasion Of Nephroblastoma

Background and Objective: Nephroblastoma, or named embryonic tumor of kidney, is the most common pediatric cancer of kidney ,affecting 1 in 10,000 children.Most cases occur before the age of 5 years,the incidence of bilateral involvement is about 5-10%. In 1899, Max Wilms described its characteristics, so it was named after his name. It is currently thought that nephroblastoma arise from metanephric blastema.If metanephric blastemas live to be undifferentiated after 36 weeks of prenatal development, those residues can be integrated into blasto-nephroblastomatosis complex and meanwhile invade kidney to proliferate.Eventually it can be evolution into malignant blastoma. Nephroblastoma ,derived from embryonic renal tissue,comprise undifferentiated blastemal cells,differentiated epithelial cells and stromal cells.There are similarities between histology of the tumor and embryonic nephrogenesis. Histological type and clinical stage are important criteria in programming remedy and predicting outcome.Now an independent prognostic molecular marker has not been identified as yet.Wnt signaling pathways are involved in the control of gene expression,cell behavior,cell adhesion and cell polarity and play a crucial and evolutionarily conserved role in directing cell fates during embryogenesis and tumorgenesis.TheWnt/p-catenin pathway is the best studied and canonical of the Wnt path ways. Inappropriate activation of this transduction pathway ,which inhibits the degradation of p-catenin,has activated the key signal transducer p-catenin.And as a result p-catenin regulate the transcription of a number of target genes,and matrix metalloproteinase-7(MMP-7) is one of these target genes.Matrix metalloproteinases (MMPs)comprise a family of structurally related enzymes which are dependent on zinc.MMP-7 is a member of the MMP family which is believed to degrade components of the extracelluar matrix(ECM).MMP-7 which is secreted only by tumor cells degrade basement membrane consisted of components of the extracellular matrix and stimulate neoplasms'invasion and metastasis.The adhension of cells to their neighbors which are regulated by E-cadherin are important for maintaining tissue architecture and limiting cell movement and proliferation.The cell-cell adhension junctions compose of E-cadherin and its associated catenins.Loss of E-cadherin expression eliminates Ajs formation and stimulates the deviateon of p-catenin from the cytoskeleton. It was closely related to malignant transformation of the cell and neoplasms' invasion.In this research expressions of the key Wnt signal regulator P-catenin with its revelant gene E-cadherin and MMP-7 are detected in nephroblastoma and non-tumor renal tissue by immunohistochemistory S-P method in order to discover involvement of Wnt/p-catenin pathway in the genesis and progression of nephroblastoma .The theoretical basis can be provided for the research to inhibit nephroblastoma metastasis and gene therapy.Materials and Methods: Thirty nephroblastoma specimens and fifteen non-neoplasia renal tissue specimens proved by pathologic diagnosis were collected from surgical resections. These neoplasitc patients whose age varied from 7 months to 9 years, average 2.6 years, are 19 males and 11 females andwere not performed any radiotherapy and chemotherapy. According to NWTS-5 criteria, histological types of their HE staining sections were classified into two groups. Among them 23 cases belonged to favorable histology (FH) type, and 7 patients were unfavorable histology (UH) type. Control group, 15 cases, consisted of 6 normal renal tissues near tumor and 9 non-neoplasia renal tissues. Each specimen was stained both in HE staining and in immunohistochemistory. Expressions of E-cadherin , p-catenin and MMP-7 in patients were detected by S-P method. The results are analysed by SPSS 10.0 statistical software.All data were classified by clinical stage,age and gender .All the statistical resultswere showed in the form of x -s. The r-test ,chi-square test and Fisher's exact probabilities were u...