CEACAM1: a novel urinary marker for bladder cancer detection

Abstract

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 noninvasive 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.