Abstract 3429: Genetic analysis of pancreatic neuroendocrine neoplasms grade 3

Pancreatic neuroendocrine neoplasms (PanNENs) are pancreatic tumors with neuroendocrine differentiation. PanNENs are classified into three grades according to the proliferating cell fraction as measured by Ki-67 or mitotic index. Among them, PanNEN grade 3 (PanNEN G3) shows the highest Ki-67 index > 20%, which is morphologically divided into two categories, well-differentiated (PanNET G3) and poorly differentiated (PanNEC) tumors. Although sharing some overlapping histological features, both tumors also differ from each other with respect of clinical characteristics. To date, the molecular basis of these difference and similarity are poorly understood. To understand their molecular pathogenesis, we performed comprehensive genetic analysis on PanNEN G3. In total, we enrolled 25 PanNEN G3 cases, including 13 PanNET G3, 10 PanNEC, and 2 PanNEN G3 NOS, which were analyzed for somatic mutations. All tumors showed neuroendocrine markers such as synaptophysin or chromogranin A. The median Ki67 index of PanNET G3 was 30.5% (15-78%), which was lower than that of PanNEC (median 70.9%, range 44-100 %). Genomic DNA was extracted from microdissected tumors and paired normal tissues from formalin-fixed paraffin-embedded PanNEN G3 specimens guided by HE 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3429.