The Correlation Between Osteosarcoma And The Expression Of Vascular Endothelial Growth Factor, Matrix Metalloproteinase

IntroductionAlthough the use of adjuvant chemotherapy and neoadjuvant chemotherapy improves the prognosis of osteosarcoma, the high ratio of metastasis is still the problem. The traditional chemotherapy has many defects, such as drug resistance. Antiangiogenic therapy, at least in theory, provides a number of important advantages over cytotoxic chemotherapy: (1) Tumor endothelium appears to be similar to each other. This finding supports the notion that agents directed against tumor endothelium will be active for a broad range of tumor types, a hope that has been supported by animal studies. (2) Tumor cells lose responsiveness to chemotherapy in part because their high mutation rate and genetic instability lead to the selection of and overgrowth by resistant clones. Antiangiogenic therapy, by contrast, targets activated epithelial cells that are nonneoplastic, diploid, and genetically stable. This has lead to the prediction that resistance may develop more slowly, or not at all, to this type of treatment, which has been borne out in certain animal models. (3) The responsiveness of a tumor to chemotherapy is also dependent on tissue particularly in poorly vascularized, hypoxic tumors.Endothelial cell, however, should be easily accessible to agents administered systemically. (4) The side effect profile for many of the agents tested thus far appears to be favorable and is generally nonoverlapping with chemotherapies. The mechanisms of antiangiogenic therapy includes three aspects: (1) Block the cytokines for angiogenesis, receptors or signal pathways; (2) Up-regulate or induce endogenous inhibitors; (3) act directly on the blood vessels of the tumor. Vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMP) are important targets for anti-angiogenic therapy. Many studies has indicated that MMPs (especially MMP-2 and MMP-9) and VEGF are associated with tumor invasion and metastasis. However, there is no report concerning the correlation between VEGF, MMP-2, MMP-9 and osteosarcoma.AimThe aim of this study was to: (1) find the possible relationship between the expression of VEGF and the expression of MMP-2 and MMP-9 in osteosarcoma; (2) detect wether the expressions of MMP-2, MMP-9 and VEGF were associated with the prognosis of osteosarcoma; (3) provide evidence for antiangiogenic therapy in clinical use for osteosarcoma.MethodsThe 56 specimens of osteosarcoma biopsy and 8 specimens of metastasis focus were from the Department of Orthopaedics in the Second Affiliated Hospital of Zhejiang University. There were 34 specimens from male and 22 specimens from female. The age of the patients was from 9 to 43 years old and the mediumage was 18 years old. Tumors were located in the distal femur in 28 patients, the proximal tibia in 12, the proximal humerus in 8, the proximal fibula in 5, the proximal femur in 2 and distal tibia in one. The number of osteoblastic osteosarcoma is 28, chondroblastic 11, fibroblastic 8 and the others 9. Thirty-seven patients carried out limb salvage surgery, 19 patients carried out amputation.The expression of VEGF, MMP-2 and MMP-9 was detected by immunohistochemical method (S-P). The metastasis lymphonode of breast cancer was used for positive control of MMP-2 and MMP-9. The colon cancer was used for positive control of VEGF. MMP-2 and MMP-9 were described by qualitative analysis: "+" means positive cell >5%. VEGF was described by half-quantitative analysis: "-" means positive cell...