CATHEPSIN-D IN INTESTINAL GANGLION-CELLS - A POTENTIAL AID TO DIAGNOSIS IN SUSPECTED HIRSCHSPRUNGS-DISEASE

There is still a need for a better method of detecting immature gangli on cells in paraffin sections of colorectal luminal biopsies in cases suspected of Hirschsprung's disease. The lysosomal aspartic proteinase cathepsin D has been immunolocalized to various cell types, including ganglion cells. We investigated its expression in intestinal ganglion cells to determine whether it could be used as an aid in the detectio n of immature ganglion cells in rectal biopsies from children suspecte d of having Hirschsprung's disease. Routinely processed tissues of eig ht adult intestines resected for gunshot wounds and six ganglioneuroma s (for mature ganglion cells), of six colons resected for neonatal nec rotizing enterocolitis (for immature ganglion cells), and of 11 cases of suspected and three cases of known Hirschsprung's disease were immu nostained with a polyclonal antibody to cathepsin D using the avidin-b iotin-peroxidase method. In all cases, all ganglion cell bodies presen t showed intense granular cytoplasmic reactivity for cathepsin D. The granules crowded the cytoplasm and formed a collarette around the nucl eus. In the submucosa, the only other immunoreactive cells were histio cytes, but they could be distinguished from ganglion cells by their ch aracteristic nuclear features and their occurrence singly and unassoci ated with nerves. The three resection specimens with Hirschsprung's di sease showed a clear transition between the ganglionic and the agangli onic segments. We conclude that cathepsin D is a promising marker of i mmature ganglion cells in cases suspected of Hirschsprung's disease.