Aims: The purpose of this study is to investigate whether the expression of MMP-9 (matrix metalloproteinase-9) is a potentially useful marker in osteosarcomas. Methods: 55 patients with stage IIB knee osteosarcomas were treated in our unit and had a median follow-up of 68 months. In addition to clinical data, MMP-1, MMP,-2, MMP-3, MMP-7, MMP-9 and MMP-13 were studied in the resection specimens, using immunohistochemical methods. The importance of all factors was studied using the log-rank test, and the overall survival of patients was calculated using Kaplan-Meier survival curves. Multiple variable analysis was carried out using Cox regression models with variables chosen forward and backward stepwise methods with deviance statistics. Signiþcance was set at p< 0.05. Results: On multiple variable analysis only the MMP-9 status of the tumour cells had a signiþcant effect on overall (p=0.032) and disease free survival (p=0.014). Conclusions: Our study shows that some post-chemotherapy osteosarcoma specimens express MMP-9 in the surviving tumour cells after chemotherapy. We believe that MMP-9 in the osteosarcoma cells which survive chemotherapy, contributes to recurrence because of the ability of these cells, to stimulate a new vascular network. The relationship between osteosarcomas and MMP-9 is worthy of further study.

Purpose: Matrix metalloproteinases are important for matrix turnover in development of metastasis and angiogenesis. Our purpose was to investigate the expression of MMP-9 and itsb prognostic significance in knee osteosarcomas.

Patients: 55 patients with osteosarcoma IIB of the knee area have been studied with respect to the expression of MMP-9 in the surviving tumour cells in the surgical resection specimens

Patients were followed up for at least two and a half years.

Methods: We studied the MMP-9 expression in the resection specimens using immunohistochemistry. The importance of the prognostic factors was assessed using single (log rank test) and multiple variable (Cox regression) analysis. Independence between the factors found significant using the log rank test was studied using the yf test. Significance was set at P< 0.05.

Results: On single variable analysis factors significantly associated with poor survival were high alkaline phosphatase at diagnosis and tumour cells expressing MMP-9 in the resection specimens. The only factor strongly associated with disease free survival was immunohistochemical status of tumour cells for MMP-9 in the resection specimens.

Percentage of necrosis after chemotherapy failed marginally to reach statistical significance.

On Cox regression analysis only MMP-9 remained significant for overall and disease free survival.

Discussion: Once new blood vessels penetrate a microscopic primary tumour or a distant metastasis, the lesions acquire the potential to grow into larger and potentially life threatening tumours. MMP-9 is a factor associated with matrix remodeling during angiogenesis and is also associated with leaky vessels because of its ability to degrade basement membranes. These two properties are very important for tumour growth and development of haematogenous metastases and we believe may explain our findings.