Urokinase-type Plasminogen Activator System In Bone Tumors, Expression And Significance

[ objective ] To detect the expression of urokinase-type plasminogen activator( uPA) and its receptor protein (uPA-R) in bone tumors and study their pathologic role and biological significance, then analyse the possible relationship between uPA and uPA-R.[ Method ] The expression , distribution and location of uPA and uPA-R proteins were investigated in 18 case of osteosarcoma ,13 cases of chondrosarcoma, 24 cases of osteochondroma and 23 cases of bone giant cell tumors (include 8 cases of pathological grade â… ,10 cases of pathological grade â…¡ and 5 cases of pathological grade â…¢ according to Jaffe classification), by using Avidin-biotin complex(ABC) immunohistochemistry.[ Results ]1. The positive expression rate of uPA and uPA-R proteins were 63.6% and 51.5% in malignant bone tumors(osteosarcoma and chondrosarcoma,), whereas those in benign tumors(osteochondroma) were 16.7% and 8.3% respectively (p<0.01) .In the invasive cases ,positive staining rate of uPA and uPA-R was 81.0% and 61.9%,while in the cases without invasion, positive staining rate of uPA and uPA-R was 41.7% and 25.0% respectively (P<0.05 ). In the cases which uPA and uPA-R expression were positive, the death rate of 5-year after surgery was 71.4% and 76.5% , whereas in the cases which uPA and uPA-R expression were negnative, the death rate of 5-year after surgery was 33.3% and 37.5% (P<0.05 ). Positive expression of uPA and uPA-R proteins were found in tumor cells and vascular endothelial cells.Using the correction analysisi, we found a positive correction between uPA and uPA-R in malignant bone tumors(r=0.774 p<0.01).2. In bone giant cell tumors, positive expression of uPA and uPA-R were detected in 10 and 8 casees (positive rate 43.5% and 34.8%) .In the cases with relapse or not, the positive expression rate of uPA and uPA-R was 66.7%, 28.6% and 66.7%,14.3% respectively, abnormally high expression of both uPA and uPA-R proteins was found in 6 cases (66.7%) . A striking statistically significant correlation existed betweenthe uPA-R expression or co-over expression of uPA, uPA-R proteins in bone giant cell tumors and its relapse (P<0.05 ) . However,there was no association between positive expression of uPA, uPA-R protein s and pathological gradation in bone giant cell tumors (P>0.05 ) .[ Conclusions ] 1, The plasminogen system activation was higher in malignant bone tumors. A significant correlation was found between uPA system and malignant tumor invasion , metastasis and prognosis, so the high level of uPA and uPA-R proteins reflects a biological behavior of malignant tumor. In the pathologic process of malignant bone tumors , uPA and uPA-R coordinate each other, leading to the matrix degradation and tumor invasion.2, Expression of uPA system in bone giant cell tumors is closely related to tumor relapse but not to its pathological gradation, the high expression of uPA or co-expression of uPA and uPA-R may reveal the relapse tendency of tumor.