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

Abstract EN

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).