| Endometrial carcinoma (EC) is the most common malignancy of the female tract ,and is increasing frequent in many advanced countries. Although the overall 5-year survival rate is 73%, the rate is low in the patients with stage III and IV. The molecular pathogenesis of EC is largely unknown. Matrix Metalloproteinases (MMPs) were initially associated with a metastatic phenotype via breakdown of the physical barrier (ECM). There is growing evidence, however, that the MMPs have an expanded role, as they are important for the creating and maintenace of a microenviroment that facilitates growth and modulates adhesion of tumors at primary and metastatic sites. MMP-7 is the most important one. Tissue Inhibitor of Metalloproteinase-1(TIMP-1) can inhibit its activity by binding with its center. E-cadherin (E-CAD) is a member of a family of transmembrane glycoproteins that mediate cell-cell adhesion by homophilic recognition in a Ca2+-dependent manner. It has been suggested that loss of E-cadherin epression leads to dissociation of tumor cells and promotes invasion. It has also been suggested that MMP-7 mediated extracellular cleavage of E-cadherin from tumor cell resulting in its dissociation from the cadherin/catenin complx.Objective: The aim of this study was to detemine the role of MMP-7, TIMP-1 and E-CAD in the cacinogenesis and development of EC and to analyse the correlation between MMP-7,TEMP-1 and E-CAD expression with the clinical or pathological features in EC.Method: We exmined MMP-7, TIMP-1, E-CAD protein expression in 13 nomal human endometrium, 16 precanertissues and 68 primary endometrial adenocacinomas by immunohistochemical method (SP method).Results: (1) MMP-7 was localized in plasma of glandular epithelium ofendometrium.Its expression was found in 6/13 (42.6%) normal endometriun , 12 of 16 (75%) precancers and 60 of 68 (88.2%) ECs.The difference of .the three groups was statistically significance (P<0.05). High level expression of MMP-7 was significantly related to histologic grade (P<0.05) and lymph node metastasis (P<0.05). The 5-year survival rate in patients with high MMP-7 expression (50.0%) was significantly lower than that in patients with non-high expression (P<0.05). (2) TIMP-1 was localized to endometrial-gland epithelium and stroma. Expression intensity of TIMP-1 in EC was significantly higher than in nomal endometrium (P=0.001). No relationship was found between TIMP-1 expression and clincopathologic parameters, prognosis in EC. (3) E-CAD is confined to membrane of nomal endometrium. Its expression in ECs was significantly lower than that in precancers and nomal endometrium (P<0.05). Expression of E-CAD decreased with the progress of FIGO stage, histologic grade, myometrial invasion and poor suvival (P<0.05). (4) In ECs, expression of E-CAD was correlated with MMP-7 negatively (R=-0.327,P<0.01).Conclusion: MMP-7 and TIMP-1 expression were found mainly in ECs. MMP-7 was related to cacinogenesis and development of ECs. TIMP-1 as inhibitor also increases with the pathogesis and developments but was low compared with MMP-7, the imbanlance between them resulted in invasion and metastasis of EC. Ours findings also indicated that the dissociation of cancers cells due to decresed expression of E-padherin faciliting invasion of EC cells. MMP-7 may cleavage E-CAD faciliting progression of ECs.
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