Elevated Urinary Levels and Urothelial Expression of Hepatocarcinoma-intestine-pancreas/Pancreatitis-associated Protein in Patients With Interstitial Cystitis

ObjectivesTo investigate the pathophysiology of interstitial cystitis (IC), we examined urinary levels and urothelial expression of human orthologue of pancreatitis-associated protein (PAP) III, namely, hepatocarcinoma-intestine-pancreas (HIP)/PAP, in patients with IC. We have previously shown that PAP III is expressed with increased frequency in the bladder urothelium in a rat cystitis model (Takahara Y, et al. J Urol. 2008;179:1603-1609).MethodsHIP/PAP levels in the urine from patients with IC were measured by enzyme-linked immunosorbent assay, and HIP/PAP expression in the bladder tissues was assessed by immunohistochemical study.ResultsThe median concentration of urinary HIP/PAP was significantly higher in patients with IC than in controls (13.67 vs 1.86 pg/mL urine, respectively, P <.0001, with Mann–Whitney U test). HIP/PAP immunoreactivity was observed in the urothelium of 88.2% of patients with IC (15/17) and in 5.9% of bladder tissues of controls (1/17). Urinary HIP/PAP levels in patients with IC were positively correlated with urinary frequency and bladder pain (r = 0.429, 0.443) and inversely correlated with mean voided urine volume (r = −0.488).ConclusionsUrinary HIP/PAP levels were significantly higher in IC patients and the apparent HIP/PAP expression in the bladder urothelium was more frequently observed among IC patients. The involvement of HIP/PAP in the pathophysiology of IC is suggested.