Chromogranin A as Serum Marker for Neuroendocrine Neoplasia: Comparison with Neuron-Specific Enolase and the -Subunit of Glycoprotein Hormones

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Abstract
Chromogranin A (CgA) is gaining acceptance as a serum marker of\ud neuroendocrine tumors. Its specificity in differentiating between\ud neuroendocrine and nonneuroendocrine tumors, its sensitivity to detect\ud small tumors, and its clinical value, compared with other neuroendocrine\ud markers, have not clearly been defined, however. The objectives of this\ud study were to evaluate the clinical usefulness of CgA as neuroendocrine\ud serum marker. Serum levels of CgA, neuron-specific enolase (NSE), and the\ud alpha-subunit of glycoprotein hormones (alpha-SU) were determined in 211\ud patients with neuroendocrine tumors and 180 control subjects with\ud nonendocrine tumors. The concentrations of CgA, NSE, and alpha-SU were\ud elevated in 50%, 43%, and 24% of patients with neuroendocrine tumors,\ud respectively. Serum CgA was most frequently increased in subjects with\ud gastrinomas (100%), pheochromocytomas (89%), carcinoid tumors (80%),\ud nonfunctioning tumors of the endocrine pancreas (69%), and medullary\ud thyroid carcinomas (50%). The highest levels were observed in subjects\ud with carcinoid tumors. NSE was most frequently elevated in patients with\ud small cell lung carcinoma (74%), and alpha-SU was most frequently elevated\ud in patients with carcinoid tumors (39%). Most subjects with elevated\ud alpha-SU levels also had elevated CgA concentrations. A significant\ud positive relationship was demonstrated between the tumor load and serum\ud CgA levels (P < 0.01, by chi 2 test). Elevated concentrations of CgA, NSE,\ud and alpha-SU were present in, respectively, 7%, 35%, and 15% of control\ud subjects. Markedly elevated serum levels of CgA, exceeding 300\ud micrograms/L, were observed in only 2% of control patients (n = 3)\ud compared to 40% of patients with neuroendocrine tumors (n = 76). We\ud conclude that CgA is the best general neuroendocrine serum marker\ud available. It has the highest specificity for the detection of\ud neuroendocrine tumors compared to the other neuroendocrine markers, NSE\ud and alpha-SU. Elevated levels are strongly correlated with tumor volume;\ud therefore, small tumors may go undetected. Although its specificity cannot\ud compete with that of the specific hormonal secretion products of most\ud neuroendocrine tumors, it can have useful clinical applications in\ud subjects with neuroendocrine tumors for whom either no marker is available\ud or the marker is inconvenient for routine clinical use

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