Immunoreactivity of N-terminal fragment of gastrin-releasing peptide as histochemical marker for pancreatobiliary duct-type cells.

Immunoreactivity of the N-terminal fragment of porcine gastrin-releasing peptide (GRP) was found, using the indirect immunoperoxidase technique, to be a good histochemical marker for the following normal human pancreatobiliary duct-type cells: epithelial cells of the intra- and extra-hepatic bile ducts, gallbladder, papilla vateri and intra- and extralobular pancreatic ducts, centroacinar cells of the pancreas, and accessory gland cells of the large pancreatobiliary duct system. These cells were stained with antiserum R-6902 which recognizes both the N- and C-terminal portions of porcine GRP; antiserum R-6903 with a specificity to the C-terminal fragment of porcine GRP failed to stain the cells. Duct-type cells in other human adult organs were almost negative with both antisera. The N-terminal fragment of the GRP of monkey and pig pancreatobiliary duct cells also showed immunoreactivity, whereas those of dog, pika, rat, chicken, frog, and trout did not. Immunoabsorption experiments confirmed that the immunoreactivity of human pancreatobiliary duct-type cells belonged to the N-terminal portion of porcine GRP. Under electron microscopy, the antigen was shown to be localized diffusely in the cytosol and partially in the nucleoplasm of the duct-type cells that contained no endocrine granules. Immunostaining with R-6902 serum was found to be useful in identifying duct-type cells in inflamed and/or fibrosing pancreatobiliary tissues. Most cells of a benign pancreatic duct tumor (microcystic adenoma) were positive with R-6902 serum. Mucosal cells of the fetal gastric antrum and intestine and some cancer cells of the stomach and colon also stained with R-6902 serum; adenocarcinoma cells and hyperplastic duct cells of the pancreatobiliary tree frequently showed less stainability. The significance of the specific detection of neuropeptide immunoreactivity on non-neuroendocrine duct-type cells is discussed.