Gastroenteropancreatic tumours and prohormones

The structures and post-translational maturation of pancreatic and gastrointestinal prohormones are reviewed with emphasis on Danish contributions to today's knowledge. The review describes general, cell-specific, and tumour-specific prohormone-processing patterns. Since prohormone-processing in endocrine tumours is often attenuated, conventional assays that measure only the phenotypic endpoint of hormone gene expression (i.e. the bioactive hormone) do not quantitate tumour activity accurately. In contrast, measurements that include also prohormones and processing intermediates provide more accurate data on hormone synthesis in gastroenteropancreatic endocrine tumours. In order to comply with such demands we have developed a new analytical principle (processing-independent analysis (PIA)) which quantitates the entire translation product irrespective of the degree of processing. The significance of PIA in routine diagnostics awaits prospective evaluation. We hope that the present review illustrates how the tumour biology of endocrine cells in the pancreas and the gut has been an essential research area in Danish gastroenterology and endocrinology--one purpose being improvement of early diagnosis of endocrine tumours in the gut and the pancreas.