A LACK OF INTESTINAL PACEMAKER (C-KIT) IN AGANGLIONIC BOWEL OF PATIENTS WITH HIRSCHSPRUNGS-DISEASE

Recent experimental studies in mice have shown that the proto-oncogene c-kit plays a key role in the development of a component of the pacem aker system that is required for generation of autonomic gut motility. These studies further suggest that interaction of the c-kit receptor and its ligand (stem cell factor, SCF) is critical for the development of the enteric nervous system. The authors investigated the presence of c-kit-positive (c-kit(+)) cells as well as the expression of SCF in bowel from 12 patients with Hirschsprung's disease (HD), 4 patients w ith total colonic aganglionosis (TCA), 2 patients with extensive agang lionosis (EA) and 14 controls, Our methods involved the use of immunoh istochemistry with antihuman c-kit sera and antihuman SCF sera. A few c-kit(+) cells were found in the muscle layers of aganglionic bowels f rom HD, TCA and EA, in contrast to many c-kit(+) cells in ganglionic b owel segments from control, HD, and TCA patients. Expression of SCF wa s identified in the muscle layers as well as in myenteric plexus of ga nglionic bowel, in contrast to its absence in the muscle layers of aga nglionic bowel specimens. A lack of c-kit and SCF might be of signific ance for autonomic gut dysmotility in aganglionic bowel segments of pa tients with HD and allied disorders such as chronic idiopathic intesti nal pseudo obstruction. Copyright (C) 1995 by W.B. Saunders Company