Nobels F R, Kwekkeboom D J, Coopmans W, Schoenmakers C H, Lindemans J, De Herder W W, Krenning E P, Bouillon R, Lamberts S W
Department of Medicine, University Hospital Dijkzigt, Rotterdam, The Netherlands.
J Clin Endocrinol Metab. 1997 Aug;82(8):2622-8. doi: 10.1210/jcem.82.8.4145.
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.
嗜铬粒蛋白A（CgA）作为神经内分泌肿瘤的血清标志物正逐渐被认可。然而，与其他神经内分泌标志物相比，其在区分神经内分泌肿瘤和非神经内分泌肿瘤方面的特异性、检测小肿瘤的敏感性以及临床价值尚未明确界定。本研究的目的是评估CgA作为神经内分泌血清标志物的临床实用性。测定了211例神经内分泌肿瘤患者和180例非内分泌肿瘤对照受试者的血清CgA、神经元特异性烯醇化酶（NSE）和糖蛋白激素α亚基（α-SU）水平。神经内分泌肿瘤患者中，CgA、NSE和α-SU浓度升高的分别占50%、43%和24%。血清CgA在胃泌素瘤患者（100%）、嗜铬细胞瘤患者（89%）、类癌患者（80%）、内分泌胰腺无功能肿瘤患者（69%）和甲状腺髓样癌患者（50%）中最常升高。类癌患者中观察到的水平最高。NSE在小细胞肺癌患者中最常升高（74%），α-SU在类癌患者中最常升高（39%）。大多数α-SU水平升高的受试者CgA浓度也升高。肿瘤负荷与血清CgA水平之间存在显著正相关（χ²检验，P < 0.01）。对照受试者中，CgA、NSE和α-SU浓度升高的分别占7%、35%和15%。对照患者中仅有2%（n = 3）血清CgA水平明显升高超过300μg/L，而神经内分泌肿瘤患者中有40%（n = 76）出现这种情况。我们得出结论，CgA是目前可用的最佳通用神经内分泌血清标志物。与其他神经内分泌标志物NSE和α-SU相比，它在检测神经内分泌肿瘤方面具有最高的特异性。水平升高与肿瘤体积密切相关；因此，小肿瘤可能未被检测到。尽管其特异性无法与大多数神经内分泌肿瘤的特定激素分泌产物相比，但对于没有可用标志物或标志物不便于常规临床使用的神经内分泌肿瘤患者，它可能具有有用的临床应用价值。
