Proprotein convertases (PC1/PC3 and PC2) in normal and neoplastic human tissues: their use as markers of neuroendocrine differentiation.

• DOI: 10.1210/jcem.80.1.7829629
• Publication Date: 2014-01-08T16:58:12Z
• Authors: L Scopsi; M Gullo; F Rilke; S Martin; D F Steiner
• Keywords: Pancreatic polypeptide; Enteroendocrine cell; Immunostaining; Chromogranin A; Colocalization

By immunocytochemistry and immunoblotting, we examined normal neoplastic human tissues with polyclonal antibodies raised against selected peptide regions of proprotein convertase-2 -3 (PC2 PC3), two proteases that have been shown to selectively cleave neuroendocrine precursor molecules at pairs basic residues. Immunoreactivity for both enzymes was detected in cells pituitary, gut, pancreas, thyroid, adrenals tumors thereof, but absent thyroid follicular cells, parathyroids, adrenal cortex, testes, a number nonneuroendocrine tissues, tumorous. Although PCs were virtually universal concomitants the system, neural phenotype (e.g. pheochromocytes Merkel cells) predominantly contained PC2, whereas classic endocrine mostly PC3. PC3 immunoreactive abundant all along gastrointestinal tract, PC2 highly expressed only pyloric antrum proximal third duodenum. Double immunostaining experiments revealed colocalization peptides, immunoreactivity gastrin, cholecystokinin, somatostatin cells. Noticeably, proportion glucagon-producing high gut low pancreatic islets glucagonomas, reverse occurred PC2. At ultrastructural level, confined mature dense core granules, site storage granins hormones. With exception parathyroid and/or expression correlated occurrence granins, canonical markers secretory granules. Immunoblotting confirmed identity immunocytochemical reactivities. It is concluded are sensitive differentiation distinct distribution patterns, these may play an important role analysis tumors.