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