New criteria of pancreatic neuroendocrine tumors depending on expression levels of transcription factors related to neural and endocrine cell development

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K10180
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Chiba University
• Principal Investigator: Yoshitomi Hideyuki 千葉大学, 大学院医学研究院, 准教授 (60375631)
• Co-Investigator(Kenkyū-buntansha): 古川 勝規 千葉大学, 大学院医学研究院, 講師 (00400987) ; 高野 重紹 千葉大学, 大学院医学研究院, 助教 (20436380) ; 宮崎 勝 国際医療福祉大学, 大学病院, 教授 (70166156) ; 加藤 厚 国際医療福祉大学, 医学部, 教授 (70344984) ; 大塚 将之 千葉大学, 大学院医学研究院, 教授 (90334185)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 神経内分泌腫瘍 / 神経内分泌癌 / Sox2 / Pdx1 / hASH1 / NeuroD

Outline of Final Research Achievements

The aim of this study is elucidate the pathophysiology and tumor biology of pancreatic neuroendocrine tumors (p-NETs). We assessed the expression of transcription factors SOX2 and Pdx1 essential for the normal fetal development of pancreatic neuroendocrine cells in 46 surgically resected p-NETs. SOX2 was positive in 6 of 46 p-NETs. 71% of NEC patients (5 of 7) showed positive for SOX2. SOX2 was specifically expressed in NEC. Patients with SOX2 positive p-NET showed the significantly shorter survival than patients with SOX2 negative p-NET. By experiments using cell line, Sox2 expression has a role to maintain stem cell related factor, c-myc and Oct4. High Pdx1 expression was seen in 25 of 46 p-NET patients. None of the NEC patients showed high Pdx1 expression. The expression patterns of SOX2 and Pdx1 highly correlated with prognosis of p-NETs. These expression patterns may represent the biological and pathophysiological difference of p-NETs and indicate the origin of tumor.

Free Research Field

消化器外科