Abnormalities of C-Kit-positive cellular network in isolated hypoganglionosis

C-Kit-positive interstitial cells of Cajal (ICCs) have a key role in the normal motility function and development of the bowel. They are pacemaker cells, which facilitate active propagation of electrical events and neurotransmission in the bowel wall. ICCs are present in the bowel as myenteric ICCs (ICC(my)S) and muscular ICCs (ICC(mus)S). The aim of this study was to examine the distribution of c-Kit-positive ICCs and their relationship to the autonomic intrinsic innervation in bowel specimens from patients with isolated hypoganglionosis.

Full-thickness large bowel specimens were obtained from 6 patients with hypoganglionosis and from 4 patients during bladder augmentation (controls). Frozen sections and whole-mount preparations were stained using c-Kit immunohistochemistry, nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase, and acetylcholinesterase (AChE) histochemistry and evaluated using normal brightfield and confocal laser scanning microscopy.

NADPH-diaphorase and AChE histochemistry findings showed characteristic histologic features of hypoganglionosis, eg, sparse and small myenteric ganglia and low or absent AChE activity in the lamina propria. Myenteric plexus in the normal bowel was surrounded by a dense network of c-Kit-positive ICC(my)S, whereas in hypoganglionosis sparse isolated ICC(my)S were found. C-Kit-positive ICC(mus)S were reduced markedly in the longitudinal and circular muscle layer and at the innermost part of the circular muscle in hypoganglionosis.

Deficient expression of c-Kit-positive myenteric and muscular ICCs in the hypoganglionic colon may contribute to the motility dysfunction in the affected bowel.