Interstitial cells of Cajal in the human normal urinary bladder and in the bladder of patients with megacystis-microcolon intestinal hypoperistalsis syndrome

OBJECTIVE: To investigate the distribution of c-kit-positive interstitial cells of Cajal (ICCs) in normal bladder and bladders from patients with megacystis-microcolon-intestinal peristalsis syndrome (MMIHS, a rare congenital and generally fatal cause of functional intestinal obstruction in the newborn), the most characteristic feature of which is abdominal distension caused by a distended unobstructed urinary bladder. PATIENTS AND METHODS: Full-thickness bladder specimens were obtained from four infants with MMIHS and four controls, and processed as paraffin-wax and frozen sections. Sections were assessed using single immunohistochemistry with monoclonal and polyclonal anti-c-kit antibodies. Anti-alpha-smooth muscle actin (SMA) antibody was used to investigate the contractile apparatus in smooth muscle cells of the urinary bladder. Specimens were examined using light and confocal scanning microscopy. RESULTS: There were many c-kit positive ICCs in the normal urinary bladder, appearing as small, long, bipolar cells with only two long and several short processes. In contrast, ICCs were absent in the MMIHS bladder. alpha-SMA immunoreactivity was lower in MMIHS urinary bladder than in control sections. CONCLUSION: This study shows for the first time the presence of c-kit-positive ICCs in the normal human urinary bladder. The lack of ICCs in the MMIHS bladder may contribute to the voiding dysfunction in this disease.