The extracellular matrix components, tenascin and fibronectin, in Hirschsprung's disease: an immunohistochemical study.

Previous in vitro studies have suggested that successful neural crest cell migration in the developing gut could be influenced by the composition of the extracellular matrix components, tenascin and fibronectin. The authors aimed to gain insight into the pathogenesis of Hirschsprung's disease (HD) by studying the distribution of tenascin and fibronectin in bowel specimens of patients with HD. Immunohistochemical examination was performed in specimens from 10 HD patients (8 aganglionic, 5 transitional, and 10 normoganglionic zones) and 18 age- and site-matched controls undergoing other types of gastrointestinal surgery. The distribution of tenascin was restricted to the basement membranes of the smooth muscle and vasculature, and in the basement membranes surrounding neuronal ganglia in all the controls and in 10 proximal normoganglionic HD specimens. More intense tenascin immunofluorescence was observed in the smooth muscle basement membranes of the muscularis externa of eight aganglionic and five transitional zones of HD. Wide-spread distribution of fibronectin was found in all the basement membranes as well as in the lamina propria and submucosa of all control and 10 normoganglionic HD sections. However, more intense immunofluorescence with fibronectin was observed in all the layers of eight aganglionic and five transitional zones of HD specimens. The present findings show that the mesenchymal and basement membrane extracellular matrix constitution is abnormal in the affected bowel of HD. Although a causal relationship has not been demonstrated, corroborative evidence from earlier animal experiments in other studies suggests that the extracellular matrix abnormalities may contribute to the pathogenesis of HD.