Peripherin: a novel marker for the immunohistochemical study of malformations of the enteric nervous system

Pheripherin is a 57-kD type III intermediate filament that is a specific marker for peripheral neruons, including enteric ganglion cells (GCs). Hence antibodies to peripherin may be used to demonstrate abnormalities of the enteric nervous system (ENS). Serial longitudinal histologic sections of formalin-fixed paraffin-embedded colons from 15 patients were immunostained for peripherin, neuron-specific enolase (NSE), neurofilaments, S-100, and synaptophysin. Ten patients had variable degrees of colonic aganglionosis (Hirschsprung's disease), three were premature in infants, and two were controls. Peripherin labeling yielded the highest number of recognizable GCs. Overall, 56%, 78%, and 80% of the peripherin-positive GCs in the myenteric plexus were identified by staining for neurofilaments, NSE, and S-100, respectively. Intramucosal GCs were detected in 4 of 10 cases of Hirschspring's disease (HD), none of which had been evident by routine histology. The other neuronal markers were less specific for intramucosal GCs than peripherin, because they also added enterochromaffin cells. Peripherin immunohistochemistry also allowed exact quantification of GC density expressed as GCs/mm colon, which is important for the diagnosis of HD-related disorders. In three cases of HD the GC density of the transition zone was markedly elevated compared with more proximal ganglionic bowel segments, consistent with neuronal intestinal dysplasia type B, and two cases of HD showed low GC density within the transition zone. Hence peripherin immunolabeling may prove to be a valuable aid in the diagnosis and classification of congenital malformations of the ENS.