METASTATIC GIANT CELL TUMOR OF BONE: RELATIONSHIP WITH UROKINASE-TYPE PLASMINOGEN ACTIVATION SYSTEM AND CLINICAL OUTCOME

Abstract

Introduction: Giant Cell Tumor (GCT) is rarely associated with lung metastases (1–4%). No prognostic factors have been reliably associated with the occurrence of lung metastases.

Since high levels of urokinase-type plasminogen activation system have been associated with cancer metastasis, purpose of this study was to investigate its expression in patients with giant cell tumor and the relationship with outcome.

Materials and Methods: Expression of urokinase-type plasminogen activation system was evaluated by immunohistochemistry in the primary lesion of 65 patients with GCT. This included urokinase-type plasminogen activator (u-PA), plasminogen activator inhibitor type 1 (PAI-1), and u-PA receptor (u-PAR). Patient population consisted of 12 cases that developed lung metastases and 53 cases that did not show metastases at last follow-up. Clinical outcome of the 2 groups was retrospectively reviewed and correlated with u-PA, PAI-1 and u-PAR expression levels.

Results: Overexpression of u-PA, PAI-1 and u-PAR was more frequent in the metastatic (92%) than non-metastatic (21%) group (p< 0.0005). Incidence of local recurrence was higher in the metastatic (67%) than non-metastatic (30%) group (p=0,024). Risk of re-recurrence after 1st local recurrence was more than 4 times higher in the metastatic than non-metastatic group (p=0.05). No differences were observed in the 2 groups with respect to age, sex, site, stage, treatment, follow-up and mortality.

Conclusions: Overexpression of urokinase-type plasminogen activation system in this study associated with an increased risk of lung metastases, local recurrence and local re-recurrence. Evaluation of urokinase-type plasminogen activation system expression levels may identify a subgroup of patients with increased risk of relapse