Inverse expression of uroplakins and inducible nitric oxide synthase in the urothelium of patients with bladder outlet obstruction

Objective To assess the expression and distribution of uroplakins, protein subunits of the asymmetric unit membrane (AUM), and inducible nitric‐oxide synthase (iNOS) in the urinary bladder urothelium of patients with bladder outlet obstruction (BOO) caused by benign prostatic hyperplasia (BPH). Patients and methods Urinary bladder urothelium samples from 15 men (mean age 69 years) with BOO secondary to BPH were processed for light and electron immunocytochemistry. Uroplakins and iNOS were detected, and areas of apical surface covered with AUM were compared with those of iNOS‐positive urothelial cells. Results Areas of superficial urothelial cells with no AUM were found in all obstructed bladder samples. The immuno‐electron microscopy showed that the uroplakin‐positive cells had the characteristic appearance of terminally differentiated umbrella cells, whereas cells from the uroplakin‐negative regions were undifferentiated, typically showing microvilli on their apical surface. iNOS was not detected in areas with continuous AUM staining, but was readily detected in the uroplakin‐negative areas. There was an inverse correlation between the intensity of uroplakin and iNOS staining. Conclusions In patients with BOO associated with BPH, some superficial urothelial cells lacked the AUM, suggesting focal compromise of the blood–urine permeability barrier. In such relatively undifferentiated urothelial zones there was an accompanying increase in the expression of iNOS, which marks perturbed urothelial differentiation and may modulate bladder response to the outlet obstruction.