Development of the human pancreas: variations and pathology. A tentative classification Translated title: Le développement du pancréas humain: variations et pathologie. Essai de classification

A method of labelling known to be appropriate for the demonstration of endocrine polypeptide (APUD) cells was found to label the cells of the neural crest in the chick embryo after as little as 72 hours' development. The method depends on the production, from an exogenous precursor, of an amine which is stored in specific granules and which is convertible by treatment with hot formaldehyde vapour into a fluorescent derivative. The whole technique is described as APUD-FIF. The application of APUD-FIF to mouse embryos shows that at the 7-8 somite stage (eight days) labelled neural crest cells migrate in large masses in a ventrad direction. At around the ninth day they colonize the developing foregut and its derivatives, including pharynx, stomach, duodenum, ultimobranchial body, and pancreas. In subsequent stages of development (up to 12 days) the cells are seen in comparatively large numbers in the gastrointestinal tract and in the pancreas. Complete proof that these early APUD cells, which demonstrably arise from the neural crest, are the precursors of all the endocrine polypeptide cells of the adult pancreas, stomach, duodenum, and small and large intestine, is not at present available. Notwithstanding a great deal of earlier evidence to the contrary, the premise seems likely to be true.

Neuron-specific enolase (NSE) is a neuronal form of the glycolytic enzyme enolase, which was first found in extracts of brain tissue, and was later shown to be present in APUD (amine precursor uptake and decarboxylation) cells and neurons of the diffuse neuroendocrine system but not in other peripheral cells. 90 neuroendocrine neoplasias (APUDomas) (including islet-cell tumours, phaeochromocytomas, medullary thyroid carcinomas, oat-cell tumours, and APUDomas of the gut, pancreas, and lung) reacted strongly with antisera to NSE. In addition, large amounts of the enzyme were found by radioimmunoassay in the tumours (mean 1626 +/- 479 SEM ng of NSE/mg protein), whereas control non-endocrine neoplasias contained less than 15 ng NSE/mg protein. Thus NSE, a specific enzyme produced in the neural and endocrine systems, was found to be produced in considerable quantities by all types of APUDomas but not in any non-endocrine tumours. NSE seems to be a useful and easily detected marker which may be used to distinguish endocrine from nonendocrine neoplasias. Clinical detection of endocrine tumours is difficult and such tumours are often missed. Use of NSE as a marker may avoid this.