Abstract
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.
Highlights
Chromogranin A (CgA) and synaptophysin (SPY) are the two most widely used immunohistochemical markers for neuroendocrine cells and their tumors, including pancreatic neuroendocrine tumors (Pan-NETs), in a pathology laboratory [1,2,3]
Each Pan-NET was first diagnosed for the presence of the specific hormone by immunostaining of four pancreatic hormones and gastrin, with which diagnosis of insulinoma, glucagonoma, PPoma, gastrinoma, and non-functioning tumor was rendered [20,21,25,26]
The specific hormone production influences the prognosis of Pan-NETs since over 90% of insulinomas are reportedly benign while non-β-cell tumors, including 60–90% of gastrinomas, 50–80% of glucagonomas, over 70% of somatostatinomas, and 40–70% of vasointestinal polypeptidomas (VIPomas) are malignant [25,26,27,28,29] and PPomas are estimated as 60–90% malignant depending on the location and sizes of the tumors [28,29]
Summary
Chromogranin A (CgA) and synaptophysin (SPY) are the two most widely used immunohistochemical markers for neuroendocrine cells and their tumors, including pancreatic neuroendocrine tumors (Pan-NETs), in a pathology laboratory [1,2,3]. CgA is a marker for neuroendocrine secretory granules (in neurons called large dense core vesicles) that store and release peptide hormones, originate from the trans-Golgi network, and constitute the regulated pathway of protein hormone secretion including all four pancreatic peptide hormones and gastrin [4]. CgA is an acidic protein with a molecular weight of 48 kDa consisting of 439 amino acids and is expressed by normal and tumor cells of the diffuse endocrine and neuroendocrine systems or by some cancer cells that can undergo neuroendocrine differentiation [5,6]. CgA belongs to the granin family, which includes CgA and Departments of Integrative Biosciences and Pathology, Oregon Health and Science University, Portland, Oregon, USA
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