Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Departments of Surgical Gastroenterology and Clinical Endocrinology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Scand J Gastroenterol. 2020 May;55(5):565-573. doi: 10.1080/00365521.2020.1759141. Epub 2020 Apr 30.
: The incidence of enteropancreatic neuroendocrine tumours (NET) is increasing. Chromogranin A (CgA) in plasma is a marker in patients suspected of NET tumours. CgA, however, is a precursor protein subjected to cellular processing that challenges quantitation and hence the use of CgA in diagnostics.: CgA concentrations in plasma sampled from 130 well-characterized patients with small intestinal NETs and from 30 healthy subjects were measured with eight commercial CgA kits, an in-house radioimmunoassay (RIA) and a processing-independent assay (PIA). For the evaluation of diagnostic accuracy, we performed regression analyses and plotted receiver-operating characteristic curves (ROC). The specificity was further assessed by size chromatography.: Five commercial assays (Thermo-Fisher, DRG Diagnostics, Eurodiagnostica (RIA and ELISA), and Phoenix), displayed a diagnostic accuracy with area under the curve (AUC) values >0.90, whereas three immunoassays (Yanaihara, CisBio RIA, and CisBio ELISA) discriminated poorly between disease stages (AUC: 0.60-0.78). Compared with the in-house assays, however, even the most accurate commercial immunoassay still missed patients with metastatic disease. Chromatography showed non-uniform patterns of large and small CgA fragments in plasma.: Available commercial immunoassays measure CgA in plasma with gross variability. Three commercial CgA immunoassays discriminate so poorly between health and disease that they should not be used. The highest diagnostic accuracy was obtained with processing-independent measurement of total CgA concentrations in plasma.
: 肠胰神经内分泌肿瘤（NET）的发病率正在上升。血浆中的嗜铬粒蛋白 A（CgA）是疑似 NET 肿瘤患者的标志物。然而，CgA 是一种前体蛋白，会经历细胞加工，这给定量带来了挑战，因此 CgA 在诊断中的应用受到限制。: 我们用 8 种商业 CgA 试剂盒、一种内部放射免疫测定法（RIA）和一种不依赖加工的测定法（PIA），测量了 130 例小肠 NET 患者和 30 例健康受试者的血浆中 CgA 浓度。为了评估诊断准确性，我们进行了回归分析并绘制了接收者操作特征曲线（ROC）。通过大小色谱进一步评估了特异性。: 5 种商业检测法（Thermo-Fisher、DRG Diagnostics、Eurodiagnostica（RIA 和 ELISA）和 Phoenix）显示出诊断准确性，曲线下面积（AUC）值>0.90，而 3 种免疫测定法（Yanaihara、CisBio RIA 和 CisBio ELISA）在疾病阶段之间的区分较差（AUC：0.60-0.78）。然而，与内部检测法相比，即使是最准确的商业免疫测定法仍会漏诊转移性疾病患者。色谱法显示血浆中 CgA 大、小片段存在非均匀模式。: 现有的商业免疫测定法在测量血浆 CgA 时存在很大的变异性。3 种商业 CgA 免疫测定法在健康和疾病之间的区分如此之差，以至于不应该使用它们。通过对血浆中总 CgA 浓度进行不依赖加工的测量，可获得最高的诊断准确性。
