Historical, current and future perspectives on gastrointestinal and pancreatic endocrine tumors

Gastrointestinal and pancreatic endocrine tumors are neoplasms of which the pathogenesis is not completely understood and of which the clinical behavior is difficult to predict. Originally, Masson suggested that the cell of origin was an endocrine cell derived from the gastrointestinal epithelium. However, Pearse showed that the endocrine cells throughout the body shared various features, among others the amine precursor uptake and decarboxylation (APUD) capacity, and postulated the neural crest as the common origin for all APUD cells, a hypothesis that received support from the scientific community for many years. Now, biologists start to elucidate the various transcription factors that drive gastrointestinal development, and it has become evident that Masson was presumably right. Transcription factors relevant for development may also operate during tumorigenesis, and their expression may determine tumor biology. With other genetic factors, they may play a role in the pathogenesis of gastrointestinal and pancreatic endocrine tumors, and perhaps, their expression will turn out to be of prognostic or therapeutic value. In this review, current knowledge on the development of endocrine cells, hypotheses on the origin of endocrine tumors, genetic alterations, and prognostic factors are discussed. It is suggested that the increasing understanding of the normal development of gastrointestinal and pancreatic endocrine cells, the accumulating data on genetic alterations in endocrine tumors and the reappraisal of the hypotheses on their pathogenesis formulated in the past may help in elucidating their pathogenesis and in more accurately predicting prognosis.