In situ localization of transthyretin-mRNA in the adult human liver, choroid plexus and pancreatic islets and in endocrine tumours of the pancreas and gut.

In situ hybridization with 35S-labeled single stranded RNA probes was used on sections from formaldehyde-fixed and paraffin-embedded tissue specimens to provide semiquantitative data on the occurrence of transthyretin(TTR)-mRNA in human liver, choroid plexus and pancreatic islets as well as in 15 endocrine tumours of the pancreas and gut. A monoclonal antibody to TTR was used for immunocytochemical identification of the protein in consecutive sections. The amount of TTR-mRNA in hepatocytes was found to be much less than that in epithelial cells of the choroid plexus. Glucagon cells of the pancreatic islets were also specifically labeled and the level of TTR-mRNA in these cells was intermediate between that of hepatocytes and choroid plexus epithelial cells. Four glucagonomas, one malignant insulinoma and two midgut carcinoids were shown to contain TTR-mRNA. The 'in situ' labeled cells were also found to be TTR immunoreactive. These findings present the first conclusive evidence for TTR synthesis in pancreatic islets and in endocrine tumours. They also establish that the high serum concentration of TTR found in some patients with endocrine tumours (notably glucagonomas) is most likely due to tumour production of TTR.