Molecular aspects of gastrinoma

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In contrast to most common adenocarcinonomas (pancreas, gastric, colon, etc), common oncogenes (ras, c-fos, myc, etc) or common tumor suppressor genes (retinoblastoma, p53, etc) do not play a prominent role in the pathogenesis or progression of most pancreatic endocrine tumors. Therefore their molecular pathogenesis is largely unknown. Furthermore, routine histological features of PETs, in contrast to most common tumors, are not predictive of their biological behavior. For these reason the long term management of these patients is difficult because of lack of prognostic tools. In addition these tumors have functional features that nonendocrine tumors do not possess and little is known of the molecular determinants of these. The longterm prospective study of gastrinoma patients is a good model to study and develop possible prognostic molecular parameters because the long term follow-up allows the identification of patients with tumors that pursue an aggressive course allowing molecular clinical correlations that are otherwise difficult because of the slow growth patterns of some of these tumors. Previous studies by us have demonstrated frequent abnormalities in the MEN1 gene, p16INK4a and HER2/neu but these abnormalities were either not predictive of aggressive behavior or weakly predictive.We have performed one additional recent study related to tumoral biological ativity. This study demonstrated the presence of secretin receptors on all gastrinomas and assessed the level of their expression as well as a secretin receptor variant that is reported to function as a dominant negative mutant and its expression in pancreatic cancers is reported to correlate with malignant behavior. Our analysis demonstrated the variant was present in all tumors but correlation of its level of expression with results of the secretin provocative test provided no evidence it was functioning in a dominant negative pattern in these gastrinomas, nor that its presence might account for a negative secretin test as previous proposed by others. Furthermore, neither its level of expression nor of the secretin receptor itself correlated with malignant behavior.These studies showed the assessment of neither the variant or the secretin receptor would be a useful predictive factor.