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Prognostic Significance of Soluble Urokinase Plasminogen Activator Receptor in Serum and Cytosol of Tumor Tissue from Patients with Primary Breast Cancer¹

Finsen Laboratory, Rigshospitalet, DK-2100 Copenhagen, Denmark [R. R., I. J. C., T. P., B. L., R. W. S., G. H-H., N. B.], and Imperial Cancer Research Fund, Molecular Oncology Laboratories, Institute of Molecular Medicine [C. H., K. S., A. L. H.] and Department of Surgery, John Radcliffe Hospital, Oxford, England [M. G.]

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 ( = 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.

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