Chromogranin A: its clinical value as marker of neuroendocrine tumours

Abstract

Chromogranin A (CgA) belongs to a family of secretory proteins that are present in densecore vesicles of neuroendocrine cells. Owing to its widespread distribution in neuroendocrine tissues, it can be used as an excellent immunohistochemical marker of neoplasms of neuroendocrine origin. It can also serve as serum marker of neuroendocrine activity because it is co-released with the peptide hormone content of the secretory granules. The serum concentration of CgA is elevated in patients with various neuroendocrine tumours. Elevated levels are strongly correlated with tumour volume. Although its sensitivity and specificity cannot compete with that of the specific hormonal secretion products of most of these tumours, it can nevertheless have useful clinical applications. Neuroendocrine tumours for which no peptide marker is available usually retain the capacity to secrete CgA. CgA can thus be used as serum marker for these so-called 'non-functioning' endocrine tumours. Moreover, in patients with carcinoids and phaeochromocytomas, CgA is a more stable and thus more easily manageable marker than plasma levels of respectively serotonin and catecholamines and their urinary metabolites. Its role as an important general neuroendocrine marker may be extended in the future by the development of immunoscintigraphy of membrane-bound CgA, allowing in vivo visualization of neuroendocrine neoplasms.

Plasma chromogranin A in patients with sporadic gastro-entero-pancreatic neuroendocrine tumors or multiple endocrine neoplasia type 1

“…Patients with renal failure or severe hepatic dysfunction were excluded from the study to avoid spuriously elevated CgA levels (3,8).…”

“…CgA immunohistochemical detection is a main step in the diagnosis of neuroendocrine tumors (NETs) (3). Also, circulating CgA levels have been claimed to be a useful marker for these tumors, with a high specificity and a sensitivity ranging from 27 to 81% depending on their origin (2 -8).…”

“…The highest CgA values have been found in patients with gastro-entero-pancreatic (GEP) NETs (4,6), and, interestingly, the so-called non-functioning tumors also frequently retain the ability to secrete significant amounts of CgA (3,4,9). However, most studies have been performed in patients with sporadic GEP NETs, although it is well known that these tumors can occur as a part of multiple endocrine neoplasia syndrome type 1 (MEN 1), which also includes parathyroid and pituitary tumors.…”

Circulating markers for endocrine tumours of the gastroenteropancreatic tract

“…For tumour diagnosis, however, it is advantageous to measure the intact molecule and thereafter if desired to measure whichever fragments that may give additional information as these may vary greatly between each tumour. 82 For diagnostic purposes, the measurement of intact CgA is the best chemical screening tool for NETs.…”

Impact of calibration fitting models on the clinical value of chromogranin A

“…Concentrations may be dependent on tumor features, such as: type, secretory activity, neuroendocrine differentiation degree and total burden (1,2). However, several lines of evidence show that the diagnostic accuracy is affected primarily by the type of assay used to measure CgA (1,(3)(4)(5). As a matter of fact, it has been reported that in healthy subjects, there is a discordance rate of ;20% between CgA concentrations measured using the two commercially available methods: immunoradiometric assay (IRMA) and enzyme-linked immunosorbent assay (ELISA) (1).…”