Mutational status in combined hepatocellular-cholangiocarcinoma

• Project/Area Number: 16K19096
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Human pathology
• Research Institution: Kurume University
• Principal Investigator: Kusano Hironori 久留米大学, 医学部, 助教 (30569380)
• Research Collaborator: YANO Hirohisa 久留米大学, 医学部, 教授 ; AKIBA Jun 久留米大学病院, 病院病理部, 教授 ; OGASAWARA Sachiko 久留米大学, 医学部, 講師 ; NAITO Yoshiki 久留米大学病院, 病院病理部, 講師 ; KONDO Reiichiro 久留米大学, 医学部, 助教 ; NAKASHIMA Osamu 久留米大学病院, 臨床検査部, 教授 ; KAGE Masayoshi 久留米大学, 医学部, 客員教授
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 混合型肝癌 / 遺伝子異常 / 肝腫瘍 / 細胆管細胞癌 / 臨床病理学的検討 / IDH1/2遺伝子変異 / 医歯薬学 / 基礎医学 / 人体病理学 / 消化器・唾液腺

Outline of Final Research Achievements

Combined hepatocellular cholangiocarcinomas (CHCs) are divided into classical type (CHC-classical) and subtypes with stem-cell features. The latter is further classified into typical subtype (CHC-SC-typical), intermediate-cell subtype (CHC-SC-int), and cholangiolocellular subtype (CHC-SC-CLC) in the recent WHO classification. In this study, we analyzed a series of CHCs to clarify the clinicopathologic features and KRAS and IDH1/2 mutational status of each subtype. Compared with other CHCs, CHCs-SC-CLC were less frequently associated with chronic viral hepatitis, showed lower levels of serum AFP and DCP, and had higher frequency of IDH1/2 mutations. Compared with intrahepatic cholangiocarcinomas, CHCs-SC-CLC showed lower incidence of vascular invasion and nodal metastasis, lower level of serum CA19-9 and lower frequency of expression of S100P. Our results suggest that CHC-SC-CLC may be a distinct entity among primary liver carcinomas.

Research Products

• [Journal Article] Clinical, Pathologic, and Genetic Features of Neonatal Dubin-Johnson Syndrome: A Multicenter Study in Japan. (2018)
  • Author(s): Togawa T, Tatsuki Mizuochi, Tokio Sugiura, Hironori Kusano, Ken Tanikawa, Takato Sasaki, Fumio Ichinose, Seiichi Kagimoto, Takahisa Tainaka, Hiroo Uchida, Shinji Saitoh
  • Journal Title: The Journal of Pediatrics Volume: - Pages: 161-167
  • DOI: 10.1016/j.jpeds.2017.12.058
  • Peer Reviewed
• [Journal Article] Insulinoma-associated protein 1 (INSM1) is a useful marker for pancreatic neuroendocrine tumor (2018)
  • Author(s): Masahiko Tanigawa, Masamichi Nakayama, Tomoki Taira, Satoshi Hattori, Yutaro Mihara, Reiichiro Kondo, Hironori Kusano, Ken Nakamura, Yushi Abe, Yusuke Ishida, Yoshinobu Okabe, Toru Hisaka, Koji Okuda, Kosuke Fujino, Takaaki Ito, Akihiko Kawahara, Yoshiki Naito, Rin Yamaguchi, Jun Akiba, Yoshito Akagi, Hirohisa Yano
  • Journal Title: Medical molecular morphology Volume: 51 Issue: 1 Pages: 32-40
  • DOI: 10.1007/s00795-017-0167-6
  • Peer Reviewed
• [Journal Article] Regulator of G-protein signaling 5 enhances portal vein invasion in hepatocellular carcinoma (2018)
  • Author(s): Yumi Umeno, Sachiko Ogasawara, Jun Akiba, Satoshi Hattori, Hironori Kusano, Osamu Nakashima, Hironori Koga, Takuji Torimura, Ryoji Yamakawa, Hirohisa Yano
  • Journal Title: Oncology Letters Volume: 15 Pages: 1763-1770
  • DOI: 10.3892/ol.2017.7474
  • Peer Reviewed / Open Access
• [Journal Article] Effect of sorafenib on des-γ-carboxyprothrombin secretion by a human hepatocellular carcinoma cell line (2017)
  • Author(s): Sachiko Ogasawara, Masamichi Nakayama, Jun Akiba, Hironori Kusano, Hirohisa Yano
  • Journal Title: Oncology letters Volume: 14 Issue: 2 Pages: 2170-2176
  • DOI: 10.3892/ol.2017.6451
  • Peer Reviewed
• [Journal Article] Muscle RAS oncogene homolog (MRAS) recurrent mutation in Borrmann type IV gastric cancer (2017)
  • Author(s): Makiko Yasumoto, Etsuko Sakamoto, Sachiko Ogasawara, Taro Isobe, Junya Kizaki, Akiko Sumi, Hironori Kusano, Jun Akiba, Takuji Torimura, Yoshito Akagi, Hiraku Itadani, Tsutomu Kobayashi, Shinichi Hasako, Masafumi Kumazaki, Shinji Mizuarai, Shinji Oie, Hirohisa Yano
  • Journal Title: Cancer medicine Volume: 6 Issue: 1 Pages: 235-244
  • DOI: 10.1002/cam4.959
  • Peer Reviewed / Open Access
• [Journal Article] The expression of arginase-1, keratin (K) 8 and K18 in combined hepatocellular-cholangiocarcinoma, subtypes with stem-cell features, intermediate-cell type (2016)
  • Author(s): Akiba J, Nakashima O, Hattori S, Naito Y, Kusano H, Kondo R, Nakayama M, Tanikawa K, Todoroki K, Umeno Y, Nakamura K, Sanada S, Yamaguchi R, Ogasawara S, Yano H.
  • Journal Title: Journal of Clinical Pathology Volume: 69 Issue: 10 Pages: 846-851
  • DOI: 10.1136/jclinpath-2015-203491
  • Peer Reviewed
• [Presentation] Comparison of clinicopathologic features and mutational status between each subtype of combined hepatocellular cholangiocarcinomas (2018)
  • Author(s): Hironori Kusano, Yoshiki Naito, Yutaro Mihara, Reiichiro Kondo, Sachiko Ogasawara, Jun Akiba, Osamu Nakashima, Hirohisa Yano
  • Organizer: United States and Canadian Academy of Pathology (USCAP) 107th Annual Meeting
  • Int'l Joint Research
• [Presentation] 細胆管細胞癌と肝内胆管癌の臨床病理学的特徴の比較 (2018)
  • Author(s): 草野弘宣, 内藤嘉紀, 三原勇太郎, 近藤礼一郎, 秋葉純, 中島収, 矢野博久
  • Organizer: 第54回日本肝癌研究会
• [Presentation] 細胆管細胞癌と混合型肝癌の臨床病理学的特徴の比較 (2017)
  • Author(s): 草野弘宣, 内藤嘉紀, 三原勇太郎, 近藤礼一郎, 秋葉純, 中島収, 矢野博久
  • Organizer: 第53回日本肝癌研究会
  • Place of Presentation: 東京
  • Year and Date: 2017-07-06
  • Invited
• [Presentation] Clinicopathological features of intraductal papillary neoplasm of the bile duct in 27 patients (2016)
  • Author(s): Naito Y, Kusano H, Taira T, Kawahara A, Kondou R, Nakayama M, Nakashima O, Akiba J, Yano H.
  • Organizer: 10th International Liver Cancer Association Annual Conference
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 2016-09-09
  • Int'l Joint Research