Chromogranin A (CgA) is present in some endocrine cells of adrenals, pituitary, pancreas, thyroid and in cells of diffuse endocrine system (DES) of gastrointestinal and respiratory system. It is co-secreted and co-released together with some amines and peptides, that are present in the neurosecretory granules. In functionally active, and non-active neuroendocrine tumors (NETs) blood CgA level is often elevated, therefore, it is accepted as a main nonspecific marker of NETs (1, 2).

Chromogranin A is an acidic protein with a molecular weight of 48 kDa that is composed of 439 amino acids (3). The human CgA gene (CHGA) is located on chromosome 14 (4). There are 10 dibasic sites in human CgA, which are potential sites for proteolytic cleavage (5). CgA occurs in two main conformations: random coil (60-65%) and alpha-helix (25-40%). Alteration of CgA conformation is pH and calcium ions dependent (6, 7). CgA is a protein binding Ca²⁺ ions. Many regions of CgA are homologous with Ca²⁺ binding protein – calmodulin (8). CgA is a member of the chromogranin family. The granin family consists of eight proteins including: CgA, chromogranin B (CgB), secretogranin II, secretogranin III, secretogranin IV, secretogranin V, secretogranin VI, VGF (9). Posttranslational processing of CgA molecule leads to the formation of smaller biologically active peptides, such as: vasostatin I, vasostatin II, chromacin, pancreastatin, WE-14, parastatin, catestin (10). These CgA-derived peptides due to their influence on the secretion of other hormone, play an indirect role in the metabolism of lipids, carbohydrates, calcium homeostasis, catecholamine secretion, and possess some activities on the cardiovascular system (e.g. vasoconstriction, vasodilatation). They participate also in regulation of secretion of some hormones (e.g. insulin, glucagon, leptin, LH, FSH, PTH), and play some role in the defense mechanism of the respiratory system (antimicrobial activity against bacteria, fungi) (11-15).

Measurement of blood CgA concentration appeared possible despite the presence in blood of circulating CgA fragments induced by proteolysis (16).

The first radioimmunoassay for measurements of chromogranin A was introduced by O’Connor and Bernstein in 1984 (17). The next generation assays were based on sandwich methods with the use of monoclonal or polyclonal antibodies (18). Currently few commercial assays are available: IRMA (CgA-RIA CT, CIS Bio International-Schering, Gif-sur-Yvette, France), DAKO chromogranin A ELISA kit (DAKO A/S, Glostrup, Denmark), RIA (EuroDiagnostica, Malmo, Sweden), TRACE (Kryptor System; B-R-A-H-M-S GmbH, Thermo Scientific, Germany). These assays differ in test structure, use different antibodies and differently calibrated standards. The applied in these assay monoclonal or polyclonal antibodies recognize different epitopes of CgA molecule and bind also some CgA fragments (19-21). Main characteristics of the mentioned method for determination of CgA are presented in table 1.

Lack of the recognized international standard for CgA, differences of methodology and specificity of the antibodies used, cause that individual CgA measurements performed with different CgA assays cannot be directly compared (22-23).