The Study On The Expression Of MMP-2, TIMP-2, VEGF In Oromaxillofacial Sarcoma And Their Correlations With Angiogenesis

Oromaxillofacial sarcomas (OMFS) have obvious difference of histology, high invasion and recurrence, distant metastasis easily and poor prognosis. Reports reveal that angiogenesis is regulated by certain stimulators and inhibitors. Angiogenesis is nessessary for growth and metastasis in almost all tumours. Matrix metalloproteinase 2 (MMP-2) can degenate type IV collagen specially. Tissue inhibitors of matrix metalloproteinase 2 (TIMP-2) can suppress MMP-2. Vascular endothelial growth factor (VEGF) is a most typical mitogen of endothelial cells and a potient angiogenesis promoting factor. Microvessl density (MVD) is a quantitative measure of angiogenesis and has been shown to be an important parameter of the biological behavior of various malignant tumours. MMP-2, TIMP-2 and VEGF expression was correlated positively with invasion, metastasis and angiogenesis of several human tumours. Recently, the angiogenesis activity of OMFS and its regulators have not been well defined yet.Objective This study evaluated the roles of MMP-2, TIMP-2, VEGF and angiogenesis in the genesis and progression of sarcoma as well as their interaction in order to understand the mechanisms of sarcogenesis, progression and angiogenesis, so as to help distinguish the malignant degree of OMFS, indicate clinicial therapeutics, assess prognosis and provide a theorectical foundation for a potential new therapeutic method (anti-angiogenesis therapeutics) of OMFS.Materials and methods 37 cases of OMFS samples, 14 cases of benign mesenchymal tumour samples and 3 cases of normal mesenchyma tissue samples were collected. Immunohistochemical streptavidin peroxidase method was used to detect the MVD and the MMP-2, TIMP-2, VEGF expression in OMFS and benign tumours. MMP-2 mRNA was detected by in situ hybridization at the same time. Statistical analysis was performed with SPSS 10.0 software, using Chi-square, Fisher's exact test and WilcoxonW test. Statistically significant level was considered as "alpha equals 0.05".Results 1 Immunohistochemistry1.1 Positive staining for MMP-2,TIMP-2 and VEGF protein was mainly observed in the cytoplasm and/or on the membrane of tumour cells as well as some mesenchymal cells. Positive staining for VEGF protein was also observed in some vascular endothelial cells. Positive staining for CD34 was observed in the cytoplasm of vascular endothelial cells.1.2 The MMP-2 positive rates were 14.29% (2 of 14) in benign tumour group and 51.35% (19 of 37) in OMFS group respectively. The MMP-2 positive rates in OMFS group were higher than that in benign tumour group (P<0.05). The TIMP-2 positive rates were 28.57% (4 of 14) in benign tumour group and 32.43% (12 of 37) in OMFS group respectively. There was no significant difference between them (P>0.05). The VEGF positive rates were 28.57% (4 of 14) in benign tumour group and 67.57% (25 of 37) in OMFS group respectively. The difference between them was significant (P<0.05).There was no positive expression of MMP-2, TIMP-2 and VEGF in mesenchymal tissue group. The MVD were 17.67 in the benign tumour group and 29.00 in the OMFS group respectively. The difference between them was significant (P<0.05).1.3 There were no significant difference between MMP-2, TIMP-2, VEGF expression and MVD in the OMFS group and the benign tumour group (P>0.05).1.4 In highly, moderately/poorly differentiated of OMFS, the positive rates of MMP-2 were 25.00% (3 of 12) and 64.00% ( 16 of 25) respectively, and there was significant difference between them (P<0.05); the positive rates of TIMP-2 were 25.00% (3 of 12) and 36.00% ( 9 of 25) respectively, and there was no significant difference between them (P>0.05); the positive rates of VEGF were 41.67% (5 of 12) and 80.00%(20 of 25) respectively, and there was significant difference between them (P<0.05); the MVD were 16.67 and 30.00 respectively, there was significant difference between them (P<0.05).1.5 In the group with lymph mode metastases and the group without lymph node metastases comparsion, the positive...