CEACAM1 IS A NEW URINARY MARKER FOR BLADDER CANCER

Abstract

INTRODUCTION AND OBJECTIVES: CEACAM1 is expressed in normal transitional epithelium (TE) of the bladder and in angiogenicly activated endothelial cells (EC) where CEACAM1 exhibits proangiogenic properties. We hypothesized that CEACAM1 was present in urine and that soluble CEACAM1 levels are elevated in patients with urothelial carcinoma of the bladder (UCB). METHODS: Immunohistochemical for CEACAM1 was performed on UCB sections from 10 patients. CEACAM1 ELISA was performed on prospectively collected voided urine specimens from healthy volunteers (n=30), patients with BPH (n=5), severe cystitis (n=5), non-muscleinvasive UCB (Tis n=17, Ta n=43, and T1 n=12), muscle-invasive UCB (n=21), or a past history of UCB but without evidence of disease (n=47). Western Blot analysis was performed on a subgroup of these subjects (healthy volunteers n=10, BPH n=3, severe cystitis n=5, UCB n=25, past history of UCB but without evidence of disease n=10). RESULTS: In normal bladder transitional epithelium, CEACAM1 expression was located in umbrella cells and there was no staining in blood vessels. In UCB specimens, CEACAM1 expression disappeared already in early stages whereas tumor-associated blood vessels now expressed CEACAM1. Western blotting revealed the presence of soluble forms of CEACAM1 in the urine of 0% of controls, 76% of non-invasive UCB patients, and 100% of invasive UCB patients. ELISA analysis confirmed that urinary levels of CEACAM1 were significantly higher in UCB patients compared to control subjects (median: 207 vs 0 ng/mL, p<0.001). Within UCB patients, urinary CEACAM1 levels were higher in patients with invasive disease compared to non-invasive disease (median: 400 vs 163 ng/ml, p<0.001). The area under the curve of urinary CEACAM1 for detecting UCB was 0.870 (95% CI: 0.810-0.931). The cut-off level of 110 ng/ml, for example, yielded a sensitivity of 74% and a specificity of 95% for detecting UCB. The sensitivity for detecting high-grade UCB was 88% and that for detecting invasive stage UCB was 100%. CONCLUSIONS: Epithelial expression of CEACAM1 disappears in early stages of UCB, while it appears in endothelial cells of newly formed blood vessels suggesting an angiogenic switch. CEACAM1 levels are measurable in urine samples of UCB patients using Western blot and ELISA assays. Urinary CEACAM1 levels discriminate with high accuracy UCB patients from non-UCB subjects. Moreover, urinary levels of CEACAM1 increased with advancing stage and grade. Larger studies are necessary to establish the diagnostic and prognostic role of this highly promising, novel marker in UCB.