Measurements of chromogranin A, chromogranin B (secretogranin I), chromogranin C (secretogranin II) and pancreastatin in plasma and urine from patients with carcinoid tumours and endocrine pancreatic tumours

Abstract

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.