Departments of Integrative Biosciences and Pathology, Oregon Health and Science University, Portland, Oregon, USA.
Bosn J Basic Med Sci. 2020 Aug 3;20(3):336-346. doi: 10.17305/bjbms.2020.4632.
The two most commonly used immunohistochemical markers for neuroendocrine cells and their tumors are chromogranin A (CgA) and synaptophysin (SPY). CgA is a marker for neuroendocrine secretory granules of four pancreatic hormones and gastrin while SPY is a marker for synaptic vesicles in neuroendocrine cells, which release classic neurotransmitters such as acetylcholine and others. CgA is involved in synthesis and secretion of peptide hormones through exocytosis while the function of SPY is elusive. Thirty-five pancreatic neuroendocrine tumors (Pan-NETs) were studied, consisting of 14 insulinomas, 8 gastrinomas, 2 glucagonomas, 6 pancreatic polypeptidomas and 5 non-functioning tumors, and were immunostained for four pancreatic hormones, gastrin, CgA, and SPY. Majority of Pan-NETs were less immunostained for the endocrine hormones and CgA than the normal pancreatic endocrine cells. CgA immunostaining mostly correlates with each hormone staining in non-β-cell tumors, while SPY immunostaining recognizes endocrine cells diffusely in the cytoplasm. CgA immunostaining is less in insulinomas than in non-β-cell tumors, and CgA immunostaining may distinguish CgA-weaker insulinomas from CgA-stronger non-β-cell tumors. CgA immunostaining may be used as an independent marker for biological aggressiveness in non-β-cell Pan-NETs. The serum CgA levels are higher in subjects harboring non-β-cell tumors than those harboring insulinomas, and the serum CgA elevates in parallel to the increasing metastatic tumor mass. Thus, CgA positive immunostaining in Pan-NETs correlates with the elevated serum levels of CgA for diagnosing CgA-positive non-β-cell Pan-NETs and the increasing serum CgA levels indicate increasing metastatic tumor mass.
两种最常用于神经内分泌细胞及其肿瘤的免疫组织化学标志物是嗜铬粒蛋白 A（CgA）和突触素（SPY）。CgA 是四种胰腺激素和胃泌素分泌颗粒的标志物，而 SPY 是神经内分泌细胞中突触小泡的标志物，这些细胞释放经典神经递质，如乙酰胆碱等。CgA 通过胞吐作用参与肽激素的合成和分泌，而 SPY 的功能尚不清楚。研究了 35 例胰腺神经内分泌肿瘤（Pan-NETs），包括 14 例胰岛素瘤、8 例胃泌素瘤、2 例胰高血糖素瘤、6 例胰多肽瘤和 5 例无功能肿瘤，并对四种胰腺激素、胃泌素、CgA 和 SPY 进行免疫染色。大多数 Pan-NETs 的内分泌激素和 CgA 免疫染色比正常胰腺内分泌细胞少。CgA 免疫染色与非-β 细胞肿瘤中每种激素染色大多相关，而 SPY 免疫染色则在细胞质中弥漫性识别内分泌细胞。胰岛素瘤中的 CgA 免疫染色比非-β 细胞肿瘤少，CgA 免疫染色可能将 CgA 较弱的胰岛素瘤与 CgA 较强的非-β 细胞肿瘤区分开来。CgA 免疫染色可作为非-β 细胞 Pan-NETs 生物学侵袭性的独立标志物。非-β 细胞肿瘤患者的血清 CgA 水平高于胰岛素瘤患者，并且血清 CgA 水平随转移性肿瘤质量的增加而平行升高。因此，Pan-NETs 中的 CgA 阳性免疫染色与升高的 CgA 血清水平相关，用于诊断 CgA 阳性非-β 细胞 Pan-NETs，而升高的血清 CgA 水平表明转移性肿瘤质量增加。
