Altered distribution of interstitial cells of Cajal in Hirschsprung disease.
BACKGROUND
Constipation or recurrent intestinal dysmotility problems are common after definitive surgical treatment in Hirschsprung disease (HD). c-Kit-positive interstitial cells of Cajal (ICCs) play a key role in the motility function and development of the gastrointestinal tract. Interstitial cells of Cajal that carry the tyrosine kinase receptor (c-Kit) develop as either myenteric ICCs or muscular ICCs under the influence of the kit ligand, which can be provided by neuronal and nonneuronal cells, for example, smooth muscle cells.


OBJECTIVE
To investigate the distribution of myenteric and muscular ICCs in different parts of the colon in HD.


METHODS
Resected bowel specimens from 8 patients with rectosigmoid HD were investigated using combined staining with c-Kit enzyme and fluorescence immunohistochemistry and acetylcholinesterase and nicotinamide adenine dinucleotide phosphate (NADPH) histochemistry in whole-mount preparations and conventional frozen sections.


RESULTS
In the normal bowel, ICCs formed a dense network surrounding the myenteric plexus and at the innermost part of the circular muscle. Myenteric ICCs were absent or sparse in the aganglionic bowel and sparse in the transitional zone. The expression of myenteric ICCs in the ganglionic bowel in HD was reduced compared to that in the normal bowel, and they formed only sparse networks. Muscular ICCs were found in the aganglionic bowel, transitional zone, and normoganglionic bowel of HD in a reduced density compared to the normal bowel.


CONCLUSIONS
This study demonstrates altered distribution of ICCs in the entire resected bowel of HD patients. This finding suggests that persistent dysmotility problems after pull-through operation in HD may be due to altered distribution and impaired function of ICCs.
Rolle
Udo
U
Children's Research Centre, Our Lady's Hospital for Sick Children, Dublin, Ireland.
Piotrowska
Anna Piaseczna
AP
Nemeth
Laszlo
L
Puri
Prem
P
D003106:Colon / Q000473:pathology*; D005260:Female; D005724:Ganglia / Q000473:pathology; D006627:Hirschsprung Disease / Q000473:pathology*; D006801:Humans; D007223:Infant; D008297:Male; D009130:Muscle, Smooth / Q000473:pathology*; D009197:Myenteric Plexus / Q000473:pathology*; D019009:Proto-Oncogene Proteins c-kit / Q000502:physiology
D019009:Proto-Oncogene Proteins c-kit