Overexpression of cathepsin B and urokinase plasminogen activator is associated with increased risk of recurrence and metastasis in patients with chondrosarcoma

BACKGROUND, Deregulation of the cellular protease network has been shown to be responsible for aggressive clinical behavior in several common human ma lignancies. In the current study, the authors evaluated the expression patt erns of proteases in patients with chondrosarcoma of bone and correlated th ese patterns with clinical outcome. METHODS. The expression levels of urokinase plasminogen activator; matrix m etalloproteinase types-1, -2, and -9; and cathepsins B and L were determine d immunohistochemically in 114 cases of chondrosarcomas of bone and were co rrelated with their clinicopathologic parameters as well as with long term follow-up data. RESULTS. Overexpression of cathepsin B was associated with a high rate of l ocal recurrence (P = 0.006) and a decreased recurrence free survival (P = 0 .005). Overexpression of urokinase plasminogen activator was associated wit h an increased rate of metastasis (P = 0.013), a decreased metastasis free survival (P = 0.016), and a decreased 5-year overall survival rate (P = 0.0 48). The univariate Cox model showed that tumor extension into soft tissue, high histologic grade, and overexpression of cathepsin B were predictors o f adverse outcome. Multivariate analysis showed only overexpression of cath epsin B and tumor extension into soft tissue to be independent predictors o f local recurrence. CONCLUSIONS. Overexpression of cathepsin B and urokinase plasminogen activa tor can be used to identify those patients with chondrosarcoma of hone who have an increased risk of local recurrence and distant metastases. (C) 2000 American Cancer Society.