Aetiology, molecular pathogenesis and genetics

Endocrine tumours of the gut and pancreas originate from cells of the diffuse endocrine system and are characterised by the production of a wide variety of bioactive substances including growth factors. Two major tumour categories are distinguished-well-differentiated and poorly differentiated neoplasms-with distinct phenotypes and significantly diverse clinical behaviour. Here, genetic background data are summarised on an anatomical basis for tumours of foregut, midgut and hindgut derivatives. For well-differentiated tumours, independent techniques identified the abnormality of multiple chromosomal sites and genes, pointing to a complex genetic background. Differences in foregut tumours compared with midgut and hindgut tumours are, however, outlined. The multiple endocrine neoplasia syndrome type 1 (MEN1) gene is reported to be involved in about one-third of sporadic foregut endocrine tumours and exceptionally in midgut and hindgut tumours. Similarly, X chromosome markers are associated with malignant behaviour in foregut tumours only. For poorly differentiated carcinomas, a high degree of chromosomal instability is the common genetic trait independent of tumour site and frequently involving the p53 gene.