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

J Egypt Natl Canc Inst. 2015 Mar;27(1):1-9. doi: 10.1016/j.jnci.2014.11.001. Epub 2014 Dec 4.

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.

Keywords: ADAM8; Endostatin; Immunohistochemistry; Osteosarcoma.

MeSH terms

  • ADAM Proteins / physiology*
  • Adolescent
  • Adult
  • Aged
  • Bone Neoplasms / metabolism*
  • Bone Neoplasms / mortality
  • Bone Neoplasms / pathology
  • Child
  • Disease Progression
  • Endostatins / physiology*
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Membrane Proteins / physiology*
  • Middle Aged
  • Multivariate Analysis
  • Osteosarcoma / metabolism*
  • Osteosarcoma / mortality
  • Osteosarcoma / pathology
  • Prognosis
  • Proportional Hazards Models
  • Young Adult

Substances

  • Endostatins
  • Membrane Proteins
  • ADAM Proteins
  • ADAM8 protein, human