The Expressions Of Matrix Metalloproteinases (MMP-2,MT1-MMP) And Tissue Inhibitor Of Metalloproteinases (TIMP-2) In Esophageal Squamous Cell Carcinoma

Objective:This study was aimed to investigate the expression of MMP-2 (matrix metalloproteinase-2), MT1-MMP (membrane type 1 matrix me-talloproteinase ) and TIMP-2( tissue inhibitor of metalloproteinase-2) in the esophageai carcinomas and in normal pericarcinomatous tissues, and to clarify the relationship between MMP/TIMP expressions(MMP-2, MT1-MMP and TIMP-2) and the depth of tumor invasion, differentiation of tumor cells, and with or without regional nodular invasion of the esophageai carcinoma. Meanwhile, the relationship between the expression of MMP-2, MT1-MMP and TIMP-2 and relapse and/or metastasis for three years after the operation of the radical esophageai carcinoma resection was also analyzed, so as to primarily make sure whether these indexes could be used to determine invasion and metastasis of esophageai carcinoma and to evaluate the prognosis for the patients with esophageai carcinoma. Methods:Immunohistochemistry was used to study the expression of MMP-2, MT1-MMP and TIMP-2 in esophageai carcinoma tissues and normal tissues in distance for 5-7CM from tumor. The intensity of theexpressions in tumor cells was analyzed by semiquantitative digital image analysis, and the relationship between their expressions and clinico-pathological parameters was analyzed by statistical methods. Results :Among 54 specimens of the esophageal carcinoma , the positive expression rate of MMP-2, MT1-MMP and TIMP-2 expression was 85. 2%, 63.0% and 87.0% respectively, while all of them were expressed a small quantity in normal esophageal epithelial tissues , and their expression in carcinomatous tissues of esophagus was significantly higher than those in normal esophageal epithelial tissues (all P<0.01). MMP-2, MT1-MMP and TIMP-2 were expressed on the micro-vascular endothelial cells in tumor stroma. This appearance was also detected in the tumor cells in the lymphatic ducts. The degree of MMP-2 and MT1-MMP expressions was well associated with the depth of tumor invasion (both P<0. 01), the invasion of the lymph nodes (both P<0. 01) and relapse and/or metastasis of the tumors for three years after the surgical procedure, and was also related to differentiation of tumor cells (both P<0. 01). The degree of TIMP-2 expression was not associated with the depth of tumor invasion , the invasion of the lymph nodes and the differentiation of tumor cells, but was related to relapse and/or metastasis of the tumors for three years after the radical esophagectomy.The expression of MMP-2 in the carcinomatous tissues of esophagus was well related to those of MTl-MMP(P<0.01), while both of them were not related to the expression of TIMP-2 in the esophageal carcinomas tissues(both P>0.05).Conclusions:The expression of MMP-2 and MT1-MMP in the esophageal carcinoma tissues may be used as indexes to judge invasion and metastasis of the esophageal carcinomas. The expression of MMP-2, MT1-MMP and TIMP-2 in the tissue of esophageal carcinoma may be used as indexes to evaluate the prognosis of esophageal carcinoma. High expression of MMP-2, MT1-MMP and TIMP-2 predict a poor prognosis in the patients with esophageal carcinoma. The ternary complex of MT1-MMP, TIMP-2, and proMMP-2 should be play pivotal role on the genesis, progress and metastasis of the esophageal carcinoma. TIMP-2 is a complicated and key role in the genesis of the esophageal carcinoma, and also may be play an important role in the chemotherapy of malignant tumor. To reduce the formation of the ternary complex of MT1-MMP, TIMP-2, and proMMP-2 and to increase the free TIMP-2 should be a new way to treat esophageal carcinoma.