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

Abstract

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

Chromogranin A and the α -subunit of glycoprotein hormones in medullary thyroid carcinoma and phaeochromocytoma

“…The specificity of CgA in this study is therefore in the same range as that previously reported using the same immunoassay (Baudin et al, 1998). None of the classic false positive CgA results were found in these patients (O'Connor et al, 1989; Takiyyudin et al, 1990;Cryer et al, 1991;Deftos, 1991; Takiyyudin et al, 1991;Nobels et al, 1997;Sanduleanu et al, 1999). Above all associated NET as part of multiple endocrine neoplasia were excluded.…”

“…Given its low sensitivity in MTC patients, CgA does not appear to be capable of competing with CT for the diagnosis of MTC. This CgA sensitivity was in the lower range of values described in previous studies (O'Connor and Deftos, 1986;Blind et al, 1992;Nobels et al, 1997). Such discrepancies may partly be explained by different biological assays used to measure CgA.…”

“…CgA detection is a major step in the diagnosis of NET (Wiedenmann and Huthner, 1989;Deftos, 1991;Öberg, 1996;Nobels et al, 1997;Ferrari et al, 1998). Elevated serum CgA levels have been demonstrated in various NET primaries with varying sensitivity (Baudin et al, 1998;Ferrari et al, 1998).…”

Significance of plasma chromogranin A determination in neuroendocrine tumour (NET) diagnosis.

“…From other authors observations the sensitivity of CgA as a marker of neuroendocrine tumors of the gastrointestinal tract varies between 10-100% with specificity of 68-100% [17,20]. Values of CgA diagnostic sensitivity and specificity available in the literature differ depending on the secretory activity and the degree of tumor and also depend on the method used to determine the concentration of CgA and accepted cut-off value [5,6,10,17,25,32].…”

“…In every case of diagnosed NET determination of CgA concentration has a significant impact on the prognosis and the choice of treatment and clinical outcome. Prognosis for the patients with NET secreting CgA is better, having a longer survival time and a prolonged time to progression [5,10,18,22,24,25].…”