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

Abstract

BackgroundA 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. AimTo determine the expression of ADAM8 and endostatin in osteosarcoma and to study their correlation with different clinicopathological parameters and patients’ outcomes. Material and methodsADAM8 and endostatin expression were immunohistochemically evaluated in 61 primary osteosarcomas and 11 pulmonary metastatic osteosarcoma lesions. ResultsAmong 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). ConclusionOur 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.