LONG-TERM TREATMENT RESULTS OF BONE SARCOMA PATIENTS WITH CONSIDERATION OF SERUM METALLOPROTEINASE LEVELS

Background: Bone sarcomas are extremely malignant prone to rapid hematogenic metastasing. Evaluation of biological marker expression by the tumor is important not only for the search of new potential chemotherapy targets, but for the assessment of the disease prognosis.
Aim: A comparative evaluation of matrix metalloproteinases (MMP)-2, -7, -9 and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the serum of patients with primary bone tumors and in healthy people to identify their potential association with the histological characteristics of the tumor and the disease prognosis.
Materials and methods: A comparative study of serum MMP-2, -7, -9, and TIMP-1 levels was performed in 54 patients with primary bone tumors (malignant, 45 patients, including central osteosarcoma in 21, periosteal osteosarcoma in 4, Ewing's sarcoma in 11, primary chondrosarcoma in 6, undifferentiated pleomorphic sarcoma in 3, and borderline giant cell tumors in 9) and in 26 healthy individuals with the use of the immunoenzyme technique (Biosource, USA, for TIMP-1 and R&D, USA, for MMP-2, -7, and -9).
Results: The TIMP-1 levels in the serum of patients with central and periosteal osteosarcomas were significantly higher than in the serum of healthy controls (р = 0.038 and p = 0.007, respectively). The MMP-9 levels in patients with bone malignancies were significantly lower than that in the normal controls (p < 0.05). There was a positive correlation between serum TIMP-1 and MMP-9 levels in patients with central, periosteal and Ewing's sarcomas (r = 0.37, p = 0.024). No significant differences in the 5-year survival rates related to serum TIMP-1, MMP-2, -7, -9 levels were found in patients with bone sarcomas. However, in those with osteosarcoma and serum MMP-2 > 160 ng/ml, the overall 5-year survival rate was 1.6-fold higher than in those with lower MMP-2 levels, and in those with ММP-9 levels < 377 ng/ml, the 5-year survival rate was 1.4-fold higher than in patients with ММP- 9 > 377 ng/ml. The worst 5-year survival (33%) was found in the patients with serum ММP-2 levels of less than 160 ng/ml and ММP-9 of more than 377 ng/ml. Conclusion: The results obtain suggest that the expression of MMP-2, MMP-9 and TIMP-1 could be associated with pathophysiological changes related to growth and metastatic process of bone sarcomas and osteosarcoma, in particular. This area could be an object for further studies on levels of these biomarkers and their prognostic value in bone malignancies.