Clinical Pathological Study On Expression Of Gelatinases And Their Inhibitors

Objective: To study the expression of matrix melloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-2 (TIMP-2), tissue inhibitors of metalloproteinase-1 (TIMP-1) and CD34 in oral squamous cell carcionoma (OSCC), and investigate the relationship about gelatinases (MMP-2, MMP-9) and their inbibitors (TIMP-1, TIMP-2) with micro vessel density (MVD) of carcinoma, so as to provide theoretic foundation for clinical diagnosis, therapy and prognosis of OSCC.Methods: The expressions of MMP-2, MMP-9, TIMP-2, TIMP-1 and CD34 were examined by immunohistochemistry S-P method in 22 cases of normal oral mucosa, 40 cases of atypical hyperplasia of oral epithelia and 65 cases of OSCC.Results: (1) The expressions of MMP-2 and MMP-9 in OSCC were significantly higher than those of atypical hyperplasia, and the expressions of MMP-2 and MMP-9 in the group of atypical hyperplasia were significantly higher than those of oral mucosa.(2) Significant correlations were found between the expression of MMP-9 and tumor size, differentiation, clinical stage and lymph-node metastasis. The expression of MMP-2 in OSCC was closely related with lymph-node metastasis, but had no relation with tumor size, differentiation and clinical stage.(3) The expressions of TIMP-1 and TIMP-2 in OSCC and atypical hyperplasia were significantly higher than those of oral mucosa. TIMP-1 expression in OSCC was significantly higher than that of atypical hyperplasia, but TIMP-2 expression showed no difference in OSCC and in the group of atypical hyperplasia.(4) Significant correlation was found between TIMP-1 expression and tumor differentiation and lymph-node metastasis, and significant correlation was also found between TIMP-2 expression and lymph-node metastasis.(5) The mean value of MVD in OSCC was significantly higher than that in atypical hyperplasia and the latter was significantly higher than that in oral mucosa. Significant correlation was found between MVD and tumor differentiation, clinical stage and lymph-node metastasis.(6) The expressions of MMP-2 and MMP-1 were closely related with MVD value, but the former was not closely related with MVD value.Conclusion: (1) The up-regulation of the expression of MMP-2, MMP-9, TIMP-2 and TIMP-1 in oral precancerous lesions and OSCC indicated that they might take an important role in the carcinogenesis of OSCC.(2) The significant relationship between MMP-2, MMP-9 and MVD indicated that MMP-2 and MMP-9 might be valuable to angiogenesis in OSCC.(3) MMP-2 MMP-9, TIMP-2 and TIMP-1 are important makers for metastasis of OSCC, it may be useful for the evaluation of the potential ability of lymph-node metastasis of OSCC to detect these markers by immunohistochemistry.