Cellular Localisation of Chromogranins and Processed Products in the Diffuse Neuroendocrine System and Related Tumours

Chromogranin A (CgA) and chromogranin B (CgB) are proteins present in secretory granules of the diffuse neuroendocrine system, with multiple pairs of basic amino acids, which are potential cleavage sites for production of biologically active peptides. We have developed antibodies against 12 defined epitopes of the CgA and 16 defined epitopes of CgB. With these, we have shown that the pancreatic neuroendocrine cells express different epitopes of the CgA and the CgB molecules. The insulin and glucagon producing cells express almost all examined epitopes of CgA and CgB, while the pancreatic polypeptide cells express some defined parts of the chromogranins and the somatostatin cells express only one CgA epitope and two CgB epitopes. Malignant endocrine pancreatic tumours show varied expression of chromogranin epitopes. The normal and neoplastic neuroendocrine cells of the gastrointestinal tract show various expressions of CgA epitopes. Thus, gastrin cells show a different expression of CgA epitopes than the enterochromaffin cells. One of the antibodies, CgA176-195, immunostained a larger cytoplasmic area than the other CgA antibodies, including the commercially available monoclonal antibody (LK2H10). In the adrenal glands, all chromaffin cells showed immunoreactivity to all region-specific chromogranin antibodies tested. By radioimmunoassay measurements we have shown that circulating plasma concentrations of different chromogranin epitopes differ between various types of tumours, indicating specific processing. We have also shown that the region-specific antibodies can be used to study biological processes. We conclude that the region-specific antibodies presented in this review are important tools to further study the biological role of chromogranins.