Expression of bcl-2 in enteric neurons in normal human bowel and Hirschsprung disease

Objective.--The bcl-2 protein has the functional role of blocking apoptosis , ie, programmed cell death. This protein is widely expressed in the develo ping central and peripheral nervous systems. The purpose of this study was to map bcl-2 expression in the human enteric nervous system, as this has no t previously been done. Methods.--Rectal specimens were obtained at autopsy of 13 fetuses at 13 to 31 weeks of gestation. Normal colon was also obtained from 5 children and 2 adults, and, in addition, ganglionic and aganglionic bowel resected in 11 patients with Hirschsprung disease was examined. Specimens were fixed in fo rmalin, embedded in paraffin, and analyzed with immunohistochemical methods , using antibodies raised against bcl-2 and neuron-specific enolase (NSE). Results.--The bcl-2 protein was expressed in myenteric and submucous gangli on cells in fetuses, children, and adults. Nerve fibers of the enteric plex uses that were bcl-2 immunoreactive were few compared with the number of NS E-immunoreactive nerve fibers. In aganglionic bowel no bcl-2- or NSE-immuno reactive ganglion cells were revealed. Results of NSE immunohistochemistry showed clearly stained hypertrophic nerve bundles, known to be of extrinsic origin, which were only weakly bcl-2 immunoreactive. Conclusion.--Expression of bcl-2 in enteric ganglion cells of the myenteric and submucous plexuses is displayed in the fetus and during childhood and is also retained in adult bowel. Immunohistochemical analysis of bcl-2 prov ides a good marker for identification of ganglion cells in Hirschsprung dis ease and may also be valuable for the diagnosis of disorders characterized by hypoganglionosis or hyperganglionosis.