Expression of a disintegrin and metalloprotease 8 and endostatin in human osteosarcoma: Implication in tumor progression and prognosis

Abstract

BACKGROUND: A disintegrin and metalloprotease 8 (ADAM8) is a trans-membrane protein, which is involved in cell adhesion, signaling and migration as well as the proteolytic cleavage of various substrates. Endostatin is a potent inhibitor of angiogenesis. ADAM8 and Endostatin have been associated with multiple malignancies. However, their role in osteosarcoma is not fully elucidated. AIM: To determine the expression of ADAM8 and endostatin in osteosarcoma and to study their correlation with different clinicopathological parameters and patients' outcomes. MATERIAL AND METHODS: ADAM8 and endostatin expression were immunohistochemically evaluated in 61 primary osteosarcomas and 11 pulmonary metastatic osteosarcoma lesions. RESULTS: Among 61 primary osteosarcomas, ADAM8 was detected in 52 tumors (85.2%) and highly expressed in 33 cases (54.1%). Positive endostatin expression was found in 28 tumors (45.9%). Higher ADAM8 and decreased endostatin expression rates in metastatic lesions compared to primary osteosarcoma were found but these differences were not statistically significant (p=0.086 & 0.558 respectively). High ADAM8 expression score and positive endostatin expression were significantly correlated with tumor size, stage and distant metastasis (p<0.05). Survival analysis showed that high ADAM8 expression was associated with poor overall survival (OS) (p=0.0002). Multivariate analysis revealed that ADAM8 expression level was an independent prognostic parameter for the OS (p=0.017). CONCLUSION: Our data suggest that ADAM8 and endostatin play a role in osteosarcoma progression. High ADAM8 expression serves as a reliable marker for poor prognosis in osteosarcoma patients.