Oncogenes, growth factors, receptor expression and proliferation markers in digestive neuroendocrine tumours. A critical reappraisal.
BACKGROUND
The main characteristic of the digestive neuroendocrine tumours (dNETs) is the low proliferating activity, even in the presence of malignant, metastatic behavior.


METHODS
Considering that dNETs are rare diseases, relatively numerous studies, often including a conspicuous number of patients, have recently investigated the molecular mechanisms of neuroendocrine tumour genesis.


RESULTS
In contrast to non-endocrine tumours of the digestive system such as carcinoma of the pancreas, colon and stomach, dNETs do not show alterations in oncogenes (ras, Myc, fos jun, Src) or in common tumor suppressor genes [p53, retinoblastoma suspectibility gene (Rb)]. MEN-1 gene alterations will likely be important in a proportion of sporadic dNETs. The role of various growth factors, novel oncogenes and tumour suppressor genes have also been investigated. However, results from these studies are non-conclusive and to date the molecular pathogenesis of these tumours has not been clarified. Studies on somatostatin receptor expression and synthetic analogues, as growth inhibitors in dNETs, although promising, have not reproduced in vivo all the antiproliferative effects showed in in vitro models.


CONCLUSIONS
Although various functional genes and molecular mechanisms have been investigated in dNETs, to date the molecular pathogenesis of these tumours remains to be elucidated.
Delle Fave
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Department of Gastrointestinal and Liver Diseases, II School of Medicine, La Sapienza University, Rome, Italy. dddhgi@tin.it
Corleto
V D
VD
D014408:Biomarkers, Tumor / Q000032:analysis*; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D005770:Gastrointestinal Neoplasms / Q000235:genetics* / Q000503:physiopathology; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006133:Growth Substances / Q000235:genetics* / Q000494:pharmacology; D006801:Humans; D009362:Neoplasm Metastasis; D018358:Neuroendocrine Tumors / Q000235:genetics* / Q000503:physiopathology; D009857:Oncogenes / Q000235:genetics*; D017481:Receptors, Somatostatin / Q000096:biosynthesis / Q000235:genetics
D014408:Biomarkers, Tumor; D006133:Growth Substances; D017481:Receptors, Somatostatin