CEACAM1: A Novel Urinary Marker for Bladder Cancer Detection

Background: Carcinoembryonic antigen-related cell adhesion molecule 1 (biliary glycoprotein; CEACAM1) is expressed in normal bladder urothelium and in angiogenically activated endothelial cells, where it exhibits proangiogenic properties. Objective: The aim of this study was to evaluate the value of urinary CEACAM1 for detection of urothelial carcinoma of the bladder (UCB). Design, setting, and participants: This prospective study included 175 patients. Measurements: Immunohistochemistry for CEACAM1 was performed on UCB sections of 10 patients. Enzyme-linked immunosorbent assay (ELISA) for CEACAM1 was performed on urine specimens of healthy volunteers (n = 30), patients with benign prostatic hyperplasia (BPH; n = 5), severe cystitis (n = 5), non-muscle-invasive UCB (n = 72), muscle-invasive UCB (n = 21), or past history of UCB without evidence of disease (n = 42). Western blot analysis was performed on a subgroup of these subjects (n = 53). Results and limitations: CEACAM1 immunostaining in normal urothelium disappears in non-invasive UCB but appears in endothelial cells of adjacent vessels. Western blotting revealed presence of CEACAM1 in the urine of no healthy volunteers, of 76% of noninvasive UCB patients, and of 100% of invasive UCB patients. ELISA analysis confirmed that urinary CEACAM1 levels were significantly higher in UCB patients compared with control subjects (median: 207 ng/ml vs 0 ng/ml; p < 0.001). The area under the curve for UCB detection was 0.870 (95% confidence interval [CI]: 0.810-0.931). In multivariable logistic regression analyses that adjusted for the effects of age and gender, higher CEACAM1 levels were associated with cancer presence (hazard ratio [HR]: 2.89; 95% CI: 2.01-4.15; p < 0.001) and muscle-invasive cancer (HR: 5.53; 95% CI: 1.68-18.24; p = 0.005). The cut-off level of 110 ng/ml yielded sensitivity of 74% and specificity of 95% for detecting UCB. Sensitivity was 88% for detecting high-grade UCB and 100% for detecting invasive-stage UCB. Larger studies are necessary to establish the diagnostic and prognostic roles of this highly promising novel marker in UCB. Conclusions: Urinary CEACAM1 levels discriminate UCB patients from non-UCB subjects. Moreover, urinary levels of CEACAM1 increased with advancing stage and grade. (c) 2009 European Association of Urology. Published by Elsevier B.V. All rights reserved.