Abstract 3401: Impact of VEGF and VEGFR polymorphisms on neuroendocrine tumors of the gastro-entero-pancreatic system (GEPNETs) outcome

Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LA Introduction: Gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) are uncommon neoplasms including a wide range of anatomical, clinical, histological and molecular malignant entities. Improving our understanding of the molecular biology of GEP-NETs represents a key challenge in the treatment of these rare tumors. Therefore we aimed to analyze genotypes of VEGF-A, VEGFR2 and Flt4 in GEP-NETs and their potential correlation with the risk of these tumors and/or with the outcome. Methods: The genomic DNA of 28 consecutive patients with GEP-NETs treated at our Institution was extracted from paraffinembedded tissue. We selected polymorphisms in the following genes: VEGF-A (rs2010963G>C, rs699947A>C), VEGFR-2 (rs2305948C>T, rs1870377T>A) and VEGFR-3 (rs307826T>C, rs307821C>A). Gene polymorphisms were determined by Real-Time PCR using TaqMan assays. Results: Median age was 58 (range 33-78) and M/F ratio was 1/1. Twenty-one out of the 28 patients had NETs of the pancreas. The allele frequency of VEGFR2 rs2305948C and of VEGFA rs2010963G showed a trend of lower frequency than in general population (82% vs. 92% and 60.3% vs. 68.8%, respectively, p<0.001). The following factors significantly correlated with a poorer overall survival (p<0.05): VEGFA rs699947C, VEGFA rs2010963A, VEGFR-2 rs1870377T/A, VEGFR-2 rs2305948C/T, VEGFR-3 rs307821C and VEGFR-3 rs307826T. Conclusion: Our results suggest, for the first time, that inherited abnormalities in VEGF pathway influence the risk and aggressiveness of GEP-NETs. Within March 2016 final data about all the enrolled 64 patients will be also available. These results should be validated prospectively in order to optimize the diagnosis and treatment of these patients. Citation Format: Rossana Berardi, Mariangela Torniai, Silvia Pagliaretta, Silvia Rinaldi, Francesca Morgese, Stefano Partelli, Miriam Caramanti, Azzurra Onofri, Vanessa Polenta, Sonia Pasquini, Massimo Falconi, Stefano Cascinu. Impact of VEGF and VEGFR polymorphisms on neuroendocrine tumors of the gastro-entero-pancreatic system (GEPNETs) outcome. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3401.