Amylin/islet amyloid polypeptide expression in medullary carcinoma of the thyroid: correlation with the expression of the related calcitonin/CGRP genes

Summary OBJECTIVE The amylin/lslet amyloid polypeptide (IAPP) gene is the third member of the calcitonin (CT)/calcitonin gene related peptide (CGRP) gene family, which includes the αCT/CGRP (CALC-I) and βCGRP (CALC-il) genes. CT is predominantly expressed in thyroid C cells, a and βCGRP (CGRP-I and II) in neural tissue and amylin/IAPP in pancreatic β cells. Both the detailed tissue distribution and the physiological role of amylln are subjects of current research. We sought to characterize the RNAs transcribed from the IAPP gene In normal human pancreas and to investigate possible ectopic expression of this gene in neuroendocrine tumours. DESIGN AND TISSUES RNA was extracted from normal human pancreas, five phaeochromocytomas and 12 medullary thyroid carcinomas (MTCs) and studied by Northern blotting. RESULTS We found that in normal human pancreas the IAPP gene transcripts differ in size from those reported for human Insulinoma. Expression of the amylin/IAPP gene was detected In seven of the MTCs, while it was not detected in phaeochromocytomas. There were no apparent clinical or histological differences between IAPP positive and IAPP negative MTCs. The relative expression levels of the four mRNAs of the CT/CGRP gene family varied between the different tumours. CONCLUSIONS Our findings are consistent with the view that ectopic hormone production may occasionally be causally related to the common origin of related genes. The possibility that IAPP may constitute a minor component of MTC amyloid should be considered.