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Endocrine Abstracts (2013) 32 S5.1 | DOI: 10.1530/endoabs.32.S5.1

University of Verona, Verona, Italy.


Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) constitute a heterogeneous group of neoplasms. In the last few decades, due to a substantial rise in incidence and prevalence, GEP-NETs have been included among the most common tumors of the gastrointestinal tract. Diagnosis could be challenging and a significant number of patients present with metastatic or unresecable disease. The development of appropriate tools for standardized prognostic stratification and the introduction of effective target therapies have opened new horizons for planning tailored surgical or medical management and follow-up programs for these complex neoplasms. An overview on the GEP-NETs’ diagnostic and prognostic criteria proposed by the recently published WHO classification and ENETS and UICC TNM staging systems is presented, focusing on their impact on the clinical and therapeutical approaches.

The genetic events underlying the tumorigenesis of this complex group of neoplams still remain to be defined. Very recently, extensive investigations have focused on the neuroendocrine tumors of pancreatic origin (PEN). Indeed, massive-scale sequencing PEN has led to the identification of alterations of genes involved in the chromatin remodelling (MEN1, DAXX, and ATRX) in up to 60% of cases. Moreover, a small subgroup of patients harbored alterations in genes (PTEN and TSC2) that negatively regulate mTOR activation, for which targeted therapy in PEN already exist. Beyond alterations in protein coding genes, survey of chromosomal status have demonstrated that a high degree of genomic instability correlates with the aggressiveness of this neoplasm. Gene silencing by promoter methylation has been advocated, but a formal demonstration of the involvement of specific genes is still lacking. Expression profiling studies are furnishing valuable lists of mRNAs and noncoding RNAs that may advance further the research to discover novel markers and/or therapeutic targets.

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