Expression Of Matrix Metalloproteinase-9(MMP-9) And Tissue Inhibitor Of Metalloproteinase-1 (TIMP-1) And MVD In Oral Squamous Cell Carcinoma

ObjectiveTo detect the expression of MMP-9,TIMP-1 and CD34 in oral squamous cell carcinomas(OSCC) and the invasive tumor front(ITF) of OSCC, to investigate microvessel density(MVD) stained by monoclonal antibody CD34. The correlations between MMP-9,TIMP-1 at ITF and MVD and clinicopathological features were analyzed.Materials & MethodsThe analysis was performed retrospectively on 54 formalin-fixed, paraffin-embedded samples from patients with primary OSCC who received operation treatment from June 1994 to December 2001 in Department of Oral and Maxillo-facial Surgery, School of Stamotology, Wuhan University. The tumor were graded using both WHO and IFG grading system respectively by two experienced pathologists;the expressions of MMP-9, TIMP-1 and CD34 were detected by immunohistochemistry(method of streptaridin-peroxidase, SP) at the ITF and other parts of the same tumor;intratumoral microvessels were determined by immunostaining using monoclonal antibody CD34;using breast carcinoma tissue as a positive control. The correlations between levels of these expression and clinicopathological features were investigated.Results1, MMP-9 and TIMP-1 were mainly expressed in the cytoplasm of tumor cells, and rarely in tumor stroma. CD34 was expressed positively in the endothelial cells, MVD was increased near the ITF.2, The degree of staining for MMP-9 , TIMP-1 , CD34 to the size of tumor was positive(P<0.05). The expression of MMP-9 in grading III was significantly stronger than that in grading I+II (P<0. 01). The difference between MMP-9 , CD34 and depth of inflicating was significant(P<0. 05). There was no differencesbetween expression of TIMP-1 and CD34 and tumor cells differentiation and TNM stage(P>0. 05).3^ The positive rate of MMP-9 and TIMP-1 at the invasive tumor front was significantly higher than that of other parts(P<0. 001). The expression of MMP-9 in ITF was associated with to the size of tumor (P<0.05), depth of inflicating(P<0.01),MVD(P<0.01), score of IFG(P<0.01)and survival time (P<0. 01) positively. The expression of TIMP-1 had a tendency to be associated negatively with a lower cell differentiation, but the association had no statistical significance;however,the relation to IFG was positive (P<0.01).4n The expression of MMP-9 at ITF and MVD were significantly correlated with survival rate (Log-rank, P<0. 05). The WHO grading, depth of inflicat-ing, IFG score and the expression of MMP-9 at ITF were significant in the univariate COX analysis. The multivariate COX linear logistic regression model showed that the depth of invasion and expression of MMP-9 at ITF were significantly independed prognostic factors for overall survival and cumulative survival for 0SCCs(P<0.05). Gender, age, the expression of TIMP-1 and MVD had no statistical significance.ConclusionThe expression of MMP-9 and TIMP-1 were closely related to the oral squamous cell carcinoma. Their expression at ITF were significantly higher than that of other parts, and were significantly correlated with the IFG score.The relation between expression of MMP-9 at ITF and MVD was positive. Positive rate of MMP-9 and high MVD could predict the high risk group of tumors, the depth of invasion and expression of MMP-9 could be valuble of predicting the prognosis of OSCC.