Prognostic significance of soluble urokinase plasminogen activator receptor in serum and cytosol of tumor tissue from patients with primary breast cancer.
Riisbro R., Christensen IJ., Piironen T., Greenall M., Larsen B., Stephens RW., Han C., Høyer-Hansen G., Smith K., Brünner N., Harris AL.
PURPOSE: The aim of the study was to evaluate the prognostic value of soluble urokinase plasminogen activator receptor (suPAR) in preoperatively obtained sera samples (s-suPAR) from breast cancer patients. EXPERIMENTAL DESIGN: suPAR levels were determined by the use of a kinetic ELISA in sera from 274 breast cancer patients and in tumor cytosols (c-suPAR) from 188 of these patients. In addition, s-suPAR levels were analyzed in 174 female blood donors. RESULTS: The mean s-suPAR level was 3.8 ng/ml (range, 1.6-9.2 ng/ml) in the patients and 3 ng/ml (range, 1.3-6.4 ng/ml) in the donors. The mean c-suPAR level was 0.55 ng/mg protein (range, 0.07-2.83 ng/mg protein). A weak but significant linear association was found between s-suPAR and age in the donors; thus, all of the s-suPAR levels were adjusted for this age dependency (aa-s-suPAR). The aa-s-suPAR levels were significantly increased in the patients as compared with the donors (P < 0.0001). No difference was found in aa-s-suPAR levels between the lymph node-positive and -negative patients (P = 0.27), and no correlation was seen between aa-s-suPAR and c-suPAR (sigma = 0.08; P = 0.71). During the follow-up period (5.9 years) 77 patients experienced a relapse and 69 died. aa-s-suPAR as a continuous variable was significantly associated with relapse-free survival [hazard ratio (HR), 1.4; 95% confidence interval (CI), 1.1-1.8; P = 0.003] and overall survival (HR, 1.6; 95% CI, 1.2-2.0; P < 0.0001). In multivariate Cox analysis including the classical prognostic parameters in breast cancer, continuous aa-s-suPAR was significantly associated with both relapse-free survival (HR, 1.4; 95% CI, 1.1-1.7; P = 0.001) and overall survival (HR, 1.4; 95% CI, 1.1-1.8; P = 0.002). In these analyses positive lymph nodes, tumor size >2 cm, and negative estrogen receptor content were also significantly associated with patient outcome. CONCLUSION: This study shows that high preoperative aa-s-suPAR levels are significantly associated with poor outcome for breast cancer patients independent of lymph node status, tumor size, and estrogen receptor status.