Oberg K
Yale J Biol Med. 1997 Sep-Dec;70(5-6):501-8.
Neuroendocrine gut and pancreatic tumors are known to contain and secret different peptide hormones and amines. During the last two decades, many radioimmunoassays and Elizas have been developed to analyze these substances in blood and urine, which has enabled clinicians to improve the diagnosis and monitoring of patients with various neuroendocrine tumors. Due to cost constraints in medical care, it is important to try to define the most useful biochemical markers from the clinical point of view. The glycoprotein chromogranin A has been shown to be a useful marker for diagnosing various neuroendocrine tumors, both by histopathology and circulating tumor markers. In patients with demonstrable endocrine tumors, about 90 percent of the patients present high circulating levels of chromogranin A. A hundred-fold increase of plasma chromogranin is seen in patients with midgut carcinoid tumors and liver metastases. The plasma levels of chromogranin A reflect the tumor mass and can be used for monitoring the patient during treatment and follow-up, although the day-to-day variation might be 30-40 percent. High circulating levels of the chromogranin A might be an indicator of bad prognosis in patients with malignant carcinoid tumors. Besides analyzing plasma chromogranin A, specific analyses such as urinary 5-HIAA in midgut carcinoid patients, serum gastrin in patients with Zollinger-Ellison syndrome and insulin/proinsulin in patients with hypoglycemia should be performed. In patients with small tumor masses or intermittent symptoms, provocative tests such as a meal stimulation test, secretin test or pentagastrin stimulation of tachykinin release can supplement the basal measurements of peptides and amines. To fully evaluate the growth potential in neuroendocrine tumors, traditional biochemical markers should be supplemented with indicators of growth proliferation (Ki-67, PCNA) and immunohistochemical staining for the adhesion molecule CD44 and the PDGF-alpha receptor. Finally, analysis of somatostatin receptor subtypes and induction of the enzymes 2-5A syntethase and PKR are of clinical value.
神经内分泌性肠道和胰腺肿瘤已知含有并分泌不同的肽类激素和胺类。在过去二十年中，已开发出许多放射免疫分析法和酶联免疫吸附测定法来分析血液和尿液中的这些物质，这使得临床医生能够改善对各种神经内分泌肿瘤患者的诊断和监测。由于医疗保健中的成本限制，从临床角度尝试确定最有用的生化标志物很重要。糖蛋白嗜铬粒蛋白A已被证明是一种用于诊断各种神经内分泌肿瘤的有用标志物，无论是通过组织病理学还是循环肿瘤标志物。在患有可证实的内分泌肿瘤的患者中，约90%的患者循环嗜铬粒蛋白A水平升高。在患有中肠类癌肿瘤和肝转移的患者中，血浆嗜铬粒蛋白可升高百倍。嗜铬粒蛋白A的血浆水平反映肿瘤大小，可用于在治疗和随访期间监测患者，尽管每日变化可能为30%-40%。嗜铬粒蛋白A的高循环水平可能是恶性类癌肿瘤患者预后不良的指标。除了分析血浆嗜铬粒蛋白A外，还应进行特定分析，如中肠类癌患者的尿5-羟吲哚乙酸、卓-艾综合征患者的血清胃泌素以及低血糖患者的胰岛素/胰岛素原。在肿瘤较小或症状间歇性发作的患者中，激发试验，如进餐刺激试验、促胰液素试验或五肽胃泌素刺激速激肽释放试验，可补充肽类和胺类的基础测量。为了全面评估神经内分泌肿瘤的生长潜力，传统生化标志物应辅以生长增殖指标（Ki-67、增殖细胞核抗原）以及粘附分子CD44和血小板衍生生长因子-α受体的免疫组织化学染色。最后，生长抑素受体亚型分析以及2-5A合成酶和蛋白激酶R的诱导具有临床价值。
