Objective: Osteosarcoma (OS) is a malignant tumor derived frommesenchymal tissue, the main site for the onset is the distal femur,proximal tibia and proximal humerus. It is the most common malignantbone tumor in the youth, occuring in about5%of our children. Before the1970s, osteosarcoma was mainly treated with surgery(amputation), and5-year survival rate was less than20%; Then Professor Rossen and so onmade a big breakthrough by applying neoadjuvant chemotherapy toosteosarcoma, making5-year survival rate of osteosarcoma increased to60%to70%. Currently limb salvage surgery (90%of limb salvage rate)combined with preoperative and postoperative neoadjuvant chemotherapyhave been applied to the limbs sarcoma, and patients’5year survival ratewas65%to70%. Nevertheless, lung metastases still occurs in about40%to50%of patients with osteosarcoma, and lung micrometastases is oftenoccurred before diagnosis, which became the most common death reasonof osteosarcoma patients. Therefore, osteosarcoma invasion andmetastasis mechanism has become a research focus.Tumor angiogenesis(TA) and the important role in tumor occurrence and development is oneof major breakthroughs in cancer research in recent years, which hasprovide a new idea for the diagnosis and treatment of cancer. Tumorgrowth required for nutrients from blood vessels, and tumor cells can alsogo through these vascular network to distant metastasis. It can be said thegrowth, invasion and metastasis of tumor are inseparably connected withtumor angiogenesis. Tumor angiogenesis dependent on the regulation andinduction of many relevant factors. both of vascular endothelial growthfactor (VEGF) and malignant melanoma cell adhesion molecule (CDl46)are the important relevant factors, which have played an important role in tumor occurrence and development.The growth and maturation of bloodvessel are highly complex and highly coordinated process, which requirea variety of ligands to sequentially activat a series of receptors. Inpathological cases, hypoxia or abnormal expression of VEGF and so oncan stimulate VEGF overexpresion, and then cause a series of signaltransduction by binding to its specific receptor (VEGFR). VEGF onendothelial cells can produce a strong mitogenic effect, stimulateendothelial cell proliferation and increase vascular permeability, therebypromote tumor growth and metastasis.CDl46is a cell adhesion molecule,which originally is found in melanoma cells. It not only is in function as a"molecular glue", but also mediates cell-cell or cell-extracellular matrixinteractions, which help with local adhesion, cytoskeletal reorganization,cell-cell interaction, cell morphology maintenance, regulation of cellmigration and proliferation. Recent studies show that CDl46is closelyrelated with the invasion and metastasis of many tumors, especially therelationship between CDl46and tumor angiogenesis has been cause awidespread attention. Many literature has reported that CDl46is highlyexpressed in a variety of tumors such as malignant melanoma, prostatecancer, liver cancer, pancreatic cancer, kidney cancer and so on, and itshigh expression in these tumors is closely related with the process oftumor recurrence and metastasis, angiogenesis and prognosis. But therelationship between CDl46, VEGF and osteosarcoma is rarely reported.We make this study in order to investigate the expression and clinicalsignificance of CDl46and VEGF in human osteosarcoma tissues andexplore their correlation with angiogenesis of OS.Methods:43cases of resected osteosarcoma specimens have beencollected from January2006to January2008in the Third Hospital ofHebei Medical University, among which20cases with lung metastasesand23cases without lung metastases. All cases were diagnosed bypathological and imaging data. Immunohistochemistry was employed todetermine the expression of CDl46and VEGF and microvessel density (MVD) in43cases of osteosarcoma(experimental group)tissues and23cases of osteochondroma(control group).Results: The positive rates of CDl46and VEGF were significantlyhigher in the OS tissues than in the osteochondroma tissues(69.77%vs.21.74%and74.42%vs.17.39%, P<0.05).MVD was markedly higher inthe OS tissue than in the osteochondroma tissue (48.68±4.00vs.20.16±2.40, P<0.05).The expression of CDl46and VEGF and MVD inthe OS tissue was significantly correlated with the Enneking stage andlung metastasis but not with the sex, the age, the pathogenic site and thesize of tumor.The MVD values in CD146positive (50.65±2.75) andVEGF positive (50.45±2.78) groups was significantly higher than thosein CD146negative (44.12±2.32)and VEGF negative (43.53±1.96) groups(P<0.05).Conclusion: Microvessel is rich in osteosarcoma, which canpromote tumor growth and metastasis; CD146and VEGF are overexpressin OS, and both of Them have a positive correlation relationship. Theexpression of CD146and VEGF in osteosarcoma have a significantrelationship with angiogenesis; CD146and VEGF closely correlate withthe development, progress and metastasis of osteosarcoma; CD146can beused as an index of prognosis and new target of osteosarcoma treatment. |