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Molecular Pathology of Pancreatic Endocrine Tumors

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Pancreatic Cancer

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Abstract:

The molecular biology of Pancreatic Endocrine Tumors (PETs) carcinogenesis is poorly understood and is generally different from that of exocrine pancreatic neoplasms. PETs represent a rare group of neoplasms with heterogenous clinico-pathological features. They are generally sporadic but can also arise within very rare hereditary syndromes, such as Multiple Endocrine Neoplasia type I (MEN-I), von Hippel-Lindau disease (VHL), Neurofibromatosis type 1 (NF1) and Tuberous Sclerosis Complex (TSC). In these syndromes although a specific genotype/phenotype association with PETs has been described, exact mechanisms leading to tumors development are still debated. Some clinical and biological features of PETs associated with hereditary syndromes are similar in sporadic cases. Allelic imbalances (i.e., gain or loss of DNA sequences) have been explored by means of different techniques in different subtypes of sporadic PETs. Overall, main genomic changes involve gain of 17q, 7q, 20q, 9p, 7p, 9q and loss of 11q, 6q, 11p, 3p, 1p, 10q, 1q, that identify the region of putative candidate Oncogenes or Tumor Suppressor Genes (TSGs) respectively. For some of them a possible relevant prognostic role has been described. “Classical” oncogenes involved in exocrine neoplasms (k-Ras, c-Jun, c-Fos) are of limited relevance in PETs; on the contrary overexpression of Src-like kinases and cyclin DI oncogene (CCNDI) have been described. As for TSGs, p53, DPC4/Smad and Rb are not implicated in PETs tumorigenesis, while for p16INK4a, TIMP-3, RASSF1A and hMLH1 more data are available, with data suggesting a role for methylation as silencing mechanism. Different molecular pathways, and the role of tyrosine kinase receptors have also been investigated in PETs (EGF, c-KIT) with interesting findings especially for VEGF and m-TOR, which encourage clinical development. Microarray analysis of expression profiles has recently been employed to investigate PETs, with a number of different strategies, even if these studies suffer from a number of limitations, mainly related with the poor repeatability and the poor concordance between different studies. However, apart from methodological limits, molecular biology studies are needed to better know this group of neoplasms, aiming at identifying novel markers and targets for therapy also highlighting relations with clinical outcome.

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Authors and Affiliations

  1. Digestive and Liver Disease Unit, II Medical School, “Sapienza,” University of Rome, S. Andrea Hospital, Rome, Italy

    Gabriele Capurso, Stefano Festa, Matteo Piciucchi, Roberto Valente & Gianfranco Delle Fave

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  1. Gabriele Capurso
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Capurso, G., Festa, S., Piciucchi, M., Valente, R., Fave, G.D. (2010). Molecular Pathology of Pancreatic Endocrine Tumors. In: Pancreatic Cancer. Springer, New York, NY. https://doi.org/10.1007/978-0-387-77498-5_7

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