Analysis of the genetic and molecular pathogenesis in enteropancreatic neuroendocrine tumors

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Enteropancreatic neuroendocrine tumors constitute a wide variety of rare lesions that are named according to the hormones that they produce. Although these tumors generally are believed to have an indolent growth pattern, the subset of tumors have an aggressive course. Unfortunately, in an individual patient there are no clinical, laboratory, or tumor histological features that reliably predict which the tumor will pursue an aggressive course. Furthermore, the molecular mechanisms responsible for the development and/or progression of Enteropancreatic neuroendocrine tumors are largely unknown.We previously demonstrated that human normal islet cells and insulinoma cells express the calcium-sensing receptor (CaR), and that the response of normal islets and insulinoma cells to change in extracellular Ca concentration was different. To investigate the genetic and molecular pathogenesis of the enteropancreatic neuroendocrine tumors, we analyzed the expression patterns of these tumors. We' ob … More tained the analysis of the data from tumor samples and extracted the some candidate genes involved in nodal metastasis of tumors. Here, we focused on the cell differentiation molecules, including NOTCH2 and PDX1 from the candidate genes. The expression patterns of PDX1, somatostatin, and serotonin were associated with the primary location of the tumors and with the tumors occurring in a sporadic fashion or a hereditary fashion. PDX1 was expressed in a115 duodenal gastrinomas, whereas its expression was reduced in 4 pancreatic tumors. Furthermore, the PDX1 was absent in the tumor occurring in a sporadic fashion, and was expressed in all tumors with MEN1. The difference in expression pattern of these genes was possibly, caused by the different origin of the tumors. Further investigation of the cell differentiated genes could result in the identification of the target genes and prognostic factors in the enteropancreatic neuroendocrine tumor. If molecular prognostic factors could be identified that accurately predicted the growth behavior of tumors in an individual patient, more aggressive treatment could be started earlier in the subset with a poor prognosis. Less