Role of interstitial cells of Cajal in motility disorders of the bowel

OBJECTIVE: Idiopathic intestinal pseudo-obstruction is characterized by the failure of the intestinal tract to propel its contents appropriately. This leads to signs and symptoms of bowel obstruction and, in the absence of an associated systemic disorder or the administration of drugs known to result in bowel dysmotility, is termed chronic idiopathic intestinal pseudo-obstruction (CIIP). Histopathologically, patients with CIIP can be characterized as having either myopathic or neuropathic forms, but the large majority of patients do not show any specific histological changes. Interstitial cells of Cajal (ICC) have been shown to be the pacemaker cells of the bowel and have been implicated in the pathogenesis of CIIP. The aim of this study was to compare the number and distribution patterns of c-kit+ ICC in CIIP in patients with mechanical bowel obstruction, other bowel motility disorders, and. normal controls. METHODS: Six patients with CIIP, six age-matched normal controls, nine patients with mechanical bowel obstruction, and 18 patients with other motility disorders (non-CIIP), including 10 with secondary intestinal pseudo-obstruction, were studied. Toluidine blue, Masson's trichrome, and S-100 immunostaining were performed in all subjects. The ICC were identified by an indirect immunoperoxidase method using a polyclonal c-kit antibody. RESULTS: All six patients with CIIP showed total absence of c-kit+ ICC. A subject with neonatal meconium ileus in the non-CIIP group showed patchy areas devoid of c-kit+ ICC amid normal areas. The c-kit+ ICC had a normal number and distribution pattern in all patients with mechanical obstruction and in the remaining 17 non-CIIP subjects. CONCLUSIONS: It seems that CIIP is characterized by a total loss of c-kit+ ICC. ICC may play an important role in the etiopathogenesis of CIIP and transient neonatal meconium syndrome, and staining for c-kit receptor may be very useful in the evaluation of motility disorders of the bowel.