Processing of precursors of gastroenteropancreatic hormones: diagnostic significance

The structures and posttranslational maturation patterns of pancreatic and gastrointestinal prohormones are reviewed with emphasis on both general and tumor-specific prohormone processing patterns. Since prohormone processing in neuroendocrine tumors is often attenuated, conventional assays that measure only the phenotypic endpoint of hormone gene expression (i.e., the bioactive hormone) do not quantitate tumor activity accurately. In contrast, measurements that also include prohormones and processing intermediates provide more accurate data on hormone synthesis in gastroenteropancreatic neuroendocrine tumors. To meet such demands we have developed an analytical principle (processing-independent analysis) which quantitates the entire translation product irrespective of the degree of processing. Prospective evaluation in routine diagnostics has shown that processing-independent analysis contributes to ensuring correct diagnosis when gastroenteropancreatic tumors are still small and tumor symptoms uncharacteristic (borderline cases).