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Cleaved Forms of the Urokinase Plasminogen Activator Receptor in Plasma Have Diagnostic Potential and Predict Postoperative Survival in Patients with Ovarian Cancer

Emir Heni¹, Christer Borgfeldt¹, Ib Jarle Christensen², Bertil Casslén¹ and Gunilla Høyer-Hansen²

Authors' Affiliations: ¹ Department of Obstetrics and Gynecology, University Hospital Lund, Lund, Sweden and ² Finsen Laboratory, Copenhagen, Denmark

Requests for reprints: Christer Borgfeldt, Department of Obstetrics and Gynecology, University Hospital Lund, SE-221 85 Lund, Sweden. Phone: 46-46-17-10-00; Fax: 46-46-15-78-68; E-mail: christer.borgfeldt{at}med.lu.se.

Purpose: To evaluate the plasma level of different forms of soluble urokinase plasminogen activator receptor (suPAR) as discriminators between malignant, borderline, and benign ovarian tumors and as prognostic markers in patients with ovarian cancer.

Experimental Design: The different suPAR forms were measured in preoperative plasma samples obtained from 335 patients with adnexal lesions using three different time-resolved fluoresence assays (TR-FIA): TR-FIA 1 measuring intact suPAR, suPAR(I-III), TR-FIA 2 measuring the total amount of suPAR(I-III) and the cleaved form, suPAR(II-III), and TR-FIA 3 measuring the liberated uPAR(I). Tumors were classified as benign (n = 211), borderline (possibly malignant; n = 30), and well (n = 19), moderately (n = 15), and poorly (n = 60) differentiated malignant.

Results: All uPAR forms as well as CA125 were statistically significant in univariate analysis discriminating between benign, borderline, and invasive tumors. Restricting the analysis of invasive tumors to early stage (I and II) showed similar results. A combination of CA125 and suPAR(I-III) + suPAR(II-III) discriminated between malignant (all stages) and benign tumors [AUC, 0.94; 95% confidence interval (95% CI), 0.90-0.98] as well as borderline and benign tumors (AUC, 0.78; 95% CI, 0.67-0.89). All suPAR forms were markers for poor prognosis in univariate analyses, and high preoperative plasma level of uPAR(I) is an independent predictor of poor prognosis (hazard ratio, 1.84; 95% CI, 1.15-2.95; P = 0.011) in multivariate analyses including age and CA125.

Conclusions: High concentration of plasma uPAR(I) is an independent preoperative marker of poor prognosis in patients with ovarian cancer. The combination of plasma suPAR(I-III) + suPAR(II-III) and CA125 discriminates between malignant and benign tumors with an AUC of 0.94.

Commentary

Urokinase-Type Plasminogen Activator Receptor: A Beacon of Malignancy?

Ronny Drapkin, Adam Clauss, and Steven Skates
Clin. Cancer Res. 2008 14: 5643-5645. [Abstract] [Full Text] [PDF]