Objective: Gastrointestinal and pancreatic neuroendocrine tumors (GEP-NETs) originate from cells of the diffuse endocrine system. Most GEP-NETs are sporadic, however, some of them, especially pancreatic endocrine tumors, may occur as part of familial syndromes. The genetic and molecular pathology of neuroendocrine tumor development is incomplete and remains largely unknown. However, the WHO classification introduced in clinical practice will give more insight into genetic and molecular changes related to tumor subtypes.

Results: In sporadic endocrine pancreatic tumors, losses of chromosome 1 and 11q as well as gain on 9q appear to be early invents in development of pancreatic tumors because they are already present in small tumors. Multiple genetic defects may accumulate with time and result in pancreatic neuroendocrine tumor progression and malignancy. Gastrointestinal endocrine tumors (carcinoids) show predominantly genetic alterations concentrated on chromosome 18. There are losses of the entire chromosome as well as smaller deletions. The most frequently reported mutated gene in gastrointestinal neuroendocrine tumors is b-catenin. Overexpression of cyclin D1 and cMyc has also been reported. Recently, a set of genes NAP1L1, MAGE-2D and MTA1 has been correlated with malignant behavior of small intestinal carcinoids.

Conclusions: Molecular profiling of GEP-NETs demonstrates that pancreatic endocrine tumors and gastrointestinal neuroendocrine tumors (carcinoids) display different genetic changes and should, therefore, be considered to be different tumor entities; thereby, also differently managed clinically. Although the number of genetic changes is higher in malignant tumors, we are still far away from defining a malignant profile in GEP-NETs.