IMMUNOHISTOCHEMICAL LOCALIZATION OF CHROMOSTATIN AND PANCREASTATIN, CHROMOGRANIN A-DERIVED BIOACTIVE PEPTIDES, IN NORMAL AND NEOPLASTIC NEUROENDOCRINE TISSUES

Despite the widespread distribution of chromogranin A (CgA) in neuroen docrine tissues, the biological function of CgA has not yet been eluci dated. The primary amino acid sequence of CgA, elucidated by cDNA anal ysis, has been revealed to include several pairs of basic amino acid r esidues that are homologous to the bioactive peptides, such as pancrea statin (PST) and chromostatin (CST). Using antibodies for human PST an d CST, the immunohistochemical localization of these peptides was inve stigated in neuroendocrine tissues, including human pituitary glands, pancreas, adrenal medulla, various types of neuroendocrine neoplasms ( 13 pheochromocytomas, 10 medullary thyroid carcinomas, 11 pancreatic e ndocrine tumors, and 19 carcinoid tumors), and the cell line QGP-1N de rived from human somatostatin-producing pancreatic endocrine tumor. Va riable immunoreactive intensities of PST and CST were seen, but both p eptides were detectable in all neuroendocrine tissues and in most of t he neoplasms. Immunoreactivity for both PST and CST was observed in 10 0 and 73%, respectively, of pancreatic endocrine tumors, all pheochrom ocytomas, and 80 and 40%, respectively, of medullary thyroid carcinoma s, as well as all nonrectal carcinoid tumors. In rectal carcinoids, ce lls immunoreactive for PST and CST were sparse. The distribution of PS T and CST was similar to that of CgA, and it is considered that these peptides are simultaneously processed from CgA, and may play roles in autocrine and paracrine regulation on various hormones in addition to their previously known functions.