Immunohistochemical Expression of Chromogranins A and B, Prohormone Convertases 2 and 3, and Amidating Enzyme in Carcinoid Tumors and Pancreatic Endocrine Tumors

Abstract

Although chromogranin A (CgA) is widely distributed in neuroendocrine tumors, the distribution of chromogranin B (CgB) has not been elucidated. Hormones produced by tumors are sometimes prohormones and not necessarily bioactive hormones. Prohormones have to be processed into bioactive peptides by prohormone convertases (PCs), and some of them have to be amidated by peptidylglycine ␣-amidating monooxygenase (PGM). Whether PCs and PGM are present or not in tumors may explain why some tumors are functioning and some are nonfunctioning. We investigated 45 carcinoids and 16 pancreatic endocrine tumors. Of the carcinoids, CgA was expressed in most of the tumors, except for the rectal and ovarian carcinoids, which expressed CgB strongly. The expressions of PC2, PC3, and PGM were 31%, 100%, and 87%, respectively. In the pancreatic tumors, CgA was expressed in all tumors, whereas CgB was not expressed in any tumor. The expressions of PC2, PC3, and PGM were 63%, 88%, and 63%, respectively. PC3 was expressed in all of the functioning tumors but not in two of the four nonfunctioning tumors. PC2 and PGM were not expressed in three of the four nonfunctioning tumors. In conclusion, expression of CgA and CgB was different depending on the tumor location. High frequency of PCs and PGM may explain why even nonfunctioning tumors produce some inconspicuous peptides.

Relevance of Lymph Node Micrometastases in Radically Resected Endobronchial Carcinoid Tumors

“…Chromogranin A is a glycoprotein located in the core of secretory granules of neuroendocrine cells, and it is used as general neuroendocrine histologic marker [24]. Cytokeratin is a component of the intermediate filament of the cytoskeleton in epithelial cells and presents high specificity in tumors derived from epithelial and neuroendocrine cells [25].…”

Consensus Guidelines for the Management of Patients with Digestive Neuroendocrine Tumours: Well-Differentiated Colon and Rectum Tumour/Carcinoma

“…Synaptophysin is seen in the small vesicles, and a sensitive marker for neuroendocrine tumours. Chromogranin is localized to the secretory granules and is positive in the majority of colorectal carcinoids, with chromogranin B also found in some tumours [6,27] . The minimum requirements for staining these tumours are therefore chromogranin and synaptophysin.…”

Practical Immunohistochemistry in Neoplastic Pathology of the Gastrointestinal Tract, Liver, Biliary Tract, and Pancreas

“…Chromogranin is the most specific marker, but its expression frequency varies based on anatomic location: up to 80% in NETs of the pancreas and GI tract proximal to the colon, but only 40% to 60% in those of the colorectum. [207][208][209] Synaptophysin is less specific but has a higher sensitivity that approaches 95% to 100%. 209 Although CD56 is also highly sensitive for NETs, it suffers from low specificity because it is widely expressed in a variety of tumors without neuroendocrine differentiation.…”