Insulin and Glucagon mRNA Expression and Prohormone Convertase Immunoreactivity in Normal and Neoplastic Pancreatic Endocrine Tissue.
Prohormone convertase (PC) 1/3 and PC2 are neuroendocrine-specific enzymes that convert prohormones to active hormones. To learn more about the role of these PCs in normal and neoplastic islet cells, we analyzed a series of pancreatic endocrine tumors to determine the role of PC1/3 and PC2 in islet cell hormone processing. In situ hybridization with insulin and glucagon probes and immunostaining with antibodies to PC1/3 and PC2 were done with 6 normal pancreases, 33 insulinomas, and 7 glucagonomas. The intensity of the reactions was graded from 0 to 3+. Normal islets stained strongly for both proinsulin and proglucagon mRNAs. Insulinomas and glucagonomas had readily detected hormone mRNAs for proinsulin and proglucagon, respectively. Normal pancreatic insulin cells stained weakly for PC1/3 (1+) and PC2 (1-2+), and glucagon cells stained weakly for PC1/3 (1-2+) and strongly for PC2 (2-3+). Both insulinomas and glucagonomas stained strongly for PC2 (2-3+) with less intense staining for PC1 (1-2+). These results indicate that PC2 is more highly expressed in insulin- and glucagon-producing pancreatic islet cell tumors and that there is increased expression of PC2 in insulinomas compared to normal insulin-producing cells.