Clinicopathological and genetic studies of intraductal papillary neoplasms of bile duct

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K19081
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Human pathology
• Research Institution: Kobe University
• Principal Investigator: FUJIKURA KOHEI 神戸大学, 医学研究科, 特命助教 (50773751)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: IPNB / 遺伝子変異 / 胆管内乳頭状腫瘍 / 胆管癌 / エクソーム解析 / 病理診断 / 予後 / 免疫形質

Outline of Final Research Achievements

Intraductal papillary neoplasms of the bile duct (IPNB) is a biliary tumor which shows predominantly intraductal growth and dilatation of affected ducts, and have a better prognosis. Here we elucidate the genetic landscape of IPNBs. In the whole exome sequencing study, mutations in APC or CTNNB1 were observed in 6/14 subjects (43%) and were mutually exclusive. In immunohistochemistry, the aberrant cytoplasmic and/or nuclear expression of β-catenin was found in not only 5/6 IPNBs with APC or CTNNB1 mutations, but also 6/8 cases with wild-type APC and CTNNB1 (total 79%). Somatic mutations were also identified in genes involved in RAS signalling, a cell cycle regulator, histone methyltransferase, and DNA mismatch repair, some of which are potentially targetable. This study suggests that activation of the Wnt/β-catenin signalling pathway is relevant to the development and progression of IPNBs. IPNBs appeared to be morphologically and genetically distinct from cholangiocarcinomas.

Free Research Field

診断病理