Chromogranins and/or
secretogranins constitute a family of water-soluble acidic
glycoproteins that are present in almost all endocrine, neuroendocrine and neuronal tissue.
Antibodies against
chromogranins have been widely used for immunohistochemical staining of endocrine tissue and tumours of neuroendocrine origin. Furthermore, measurements of circulating
chromogranin A have been used as a reliable marker for neuroendocrine tumour growth. In this study, we describe the development of specific
antibodies against
chromogranin A,
chromogranin B (
secretogranin I),
chromogranin C (
secretogranin II) and
pancreastatin. The
antibodies were used for immunohistochemical staining of normal and neoplastic neuroendocrine tissue and development of reliable radioimmunoassays for
chromogranin A,
chromogranin B,
chromogranin C and
pancreastatin. In 44 patients with
carcinoid tumours, 17 patients with sporadic endocrine pancreatic tumours and 11 patients with endocrine pancreatic tumours and the
multiple endocrine neoplasia 1 syndrome, plasma measurements revealed elevated
chromogranin A levels in 99%, elevated
chromogranin B in 88%, elevated
chromogranin C in 6% and elevated
pancreastatin in 46% of the patients. Urinary measurements revealed elevated levels in 39%, 15%, 14% and 33% of the patients respectively. Gel permeation chromatography of plasma and urine showed that circulating
chromogranin A, and immunoreactive fragments of
chromogranin A, had a higher molecular weight distribution than the
chromogranin A fragments excreted to the urine. Furthermore, it was noted that most of the patients excreting
chromogranin A fragments to the urine had previously been treated with
streptozotocin, a
cytotoxic agent known to induce renal tubular dysfunction. The
antibodies raised proved useful for immunohistochemical staining and visualised endocrine cells in pancreatic islets, adrenal medulla and the small intestine as well as in endocrine pancreatic tumours,
pheochromocytoma and midgut
carcinoid tumours. In conclusion, the
antibodies raised were useful for both immunohistochemical staining of normal tissue and endocrine tumours as well as development of specific radioimmunoassays for plasma measurements of the different
chromogranins. Furthermore, we show that plasma measurements of
chromogranin A and B were superior to measurements of
chromogranin C and
pancreastatin and plasma measurements of the different
chromogranins were more reliable as markers for tumour growth than the corresponding urine measurements.