The Expression And Significance Of Extracellular Matrix Metalloproteinase Inducer And Matrix Metalloproteinsaes In Epithelial Ovarian Tumor Tissue

Objectives To study the expression and significance of matrix metalloproteinases-2, 9 (MMP-2, 9), tissue inhibitors of metalloproteinases-2 (TIMP-2), extracellular matrix metalloproteinase inducer (EMMPRIN) and their relationship with the invasion, metastasis and biological behavior of epithelial ovarian cancer (EOC).Methods The paraffin blocks of 64 primary epithelial ovarian tumors (EOT) were obtained from the surgical archives of the Department of Pathology, QiLu Hospital of Shan Dong University from 1997 to 2001. The expression of MMP-2, 9, TIMP-2 and EMMPRIN in 47 patients with epithelial ovarian carcinoma and 17 patients with benign neoplasm was determinded by immunohistochemistry (IHC) and was analyzed their relationship to many clinicopatholgical parameters.Results MMP-2, 9, TIMP-2 and EMMPRIN protein were detected in primary tumor cells and stromal cells, but preminately in the tumor cells. The expression rates of MMP-2,9 protein in the EOC tissue were 78.7%(37/47), 70%(31/47), respectively, higher than their positive expression rates in benign ovarian tumors, which were58.8%(10/17), 41.2% (7/17) respectively. There was no significant difference between EOC tissue and benign ovarian tumor tissue (X2=1.6169,P>0.05; X2=3.1287, P>0.05). The expression rate of TIMP-2 protein in EOC tissue and in benign one was 78.7%(37/47) and 47.1%(8/17), respectively, the difference was significant (X2=5.9029, P<0.05). The expression of MMP-2, 9 had a significant relevance with clinical stage and lymphnodes metastases in EOC tissue. The positive expression rates were 86.4%(32/37^ 75.7 %(28/37) in stages III—IV of ovarian cancer, respectively, which were much higher than that of 50.0% (5/10), 30.0 %(3/40) in stages I-II (X2=4.2682 , P<0.05;X2 =5.4218,P<0.05).The positive expression rates of MMP-2 ,MMP-9 94.7%(18/19), 78.9%(15/19) were significantly higher in G3 than those in G1-2 EOC, which were 60.7% (17/28), 39.2 (11/28), respectively. The difference was significant (X2=5.2179, P<0.05; X2=7.0505, P<0.05). The positive expression rates of MMP-2, 9 were higher in EOC with lymphnodes metastases than those with non-lymphnodes metastases in EOC. The difference was significant (X2=5.4435, P<0.05; X2=5.9093, P<0.05). The positive expression of TIMP-2 was reverse to the expression of MMP-2 and MMP-9 on clinical stage, cell grades and lymphnodes metastases in EOC. The expression rate of EMMPRIN in EOC was 55.3 %(26/47),while there was no expression in benign EOT tissue.In EOC,the expression of EMMPRIN was associated with clinical stage,The expression rate in stage III-IV 89.1% (33/37) was significantly higher than that of EOC in stage I ~ II 50%(5/10)( X2=5.4831, PO.05). There was no significant correlation between the expression of EMMPRIN and cell grades (X2=0.2773, P>0.05). The positve expression rates of EMMPRIN 86.9%(20/23) was significantly higher in those with lymphnodes metastases than those non-lymphnode metastasis 54.1% (13/24), the difference was significant (X2=5.9093, PO.05).Conclusions (1)The expression rates of MMP-2,9, TIMP-2 and EMMPRINprotein were significantly higher in EOC tissue than in benign one, but there was no significant difference between EOC and benign ovarian tumor. The expression of TIMP-2 protein was significantly higher in EOC tissue than in benign one.(2)The expression of MMP-2, 9 and TIMP-2 correlated with tumor stages, cell grades and lymphonodes metastases in EOC (P<0.05). (3)The expression rate of EMMPRIN was significantly higher in EOC than in benign one and associated with tumor stage and lymphonodes metastases in EOC, while no relationship with cell grades.