Establishment of new diagnostic approach for the primary unknown metastatic bone tumor

• Project/Area Number: 26670286
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Laboratory medicine
• Research Institution: Juntendo University
• Principal Investigator: SAITO Tsuyoshi 順天堂大学, 医学部, 准教授 (80439736)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 原発不明癌 / バイオマーカー / 病理診断 / 診断マーカー / 骨転移 / デノスマブ / 甲状腺乳頭癌 / 肺腺癌

Outline of Final Research Achievements

We are trying to find biomarkers that can help to diagnose the primary unknown metastatic carcinomas. In this process, we identified that PPP2R1A mutations frequently occurred in GIST and that patients with GIST having this mutation showed adverse clinical outcome. We also showed that the type of NAB2-STAT6 fusion, which is specifically observed in solitary fibrous tumor (SFT), affects patients' prognosis. Furthermore, TERT promoter mutation and TP53 mutation were associated with the acquisition of the aggressive behavior, especially in the process of dedifferentiation of this tumor. We have previously shown that lung adenocarcinoma was the most common carcinoma among the primary unknown metastatic bone tumors. We also showed that galectin-4 could be a diagnostic marker for the metastatic lung adenocarcinoma, because the metastatic lung adenocarcinomas tend to lose TTF-1 expression, a marker of lung adenocarcinoma, while keeping the galectin-4 expression at the metastatic sites.

Research Products

• [Journal Article] Clinicopathological effects of protein phosphatase 2, regulatory subunit A, alpha mutations in gastrointestinal stromal tumors (2016)
  • Author(s): Ishii M, Akaike K, Suehara Y, Mukaihara K, Kubota K , Kohsaka S, Okubo T, Mitani K, Mogushi K, Takagi T, Kaneko K, Yao T, Saito T.
  • Journal Title: Modern Pathology. Volume: 29 Issue: 11 Pages: 1424-1432
  • DOI: 10.1038/modpathol.2016.138
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] In Japanese patients with papillary thyroid carcinoma TERT promoter mutation is associated with poor prognosis, in contrast to BRAFV600E mutation. (2016)
  • Author(s): Nasirden A, Saito T, Fukumura Y, Hara K, Akaike K, Kurisaki-Arakawa A, Asahina M, Yamashita A, Tomomasa R, Hayashi T, Arakawa A, Yao T.
  • Journal Title: Virchows Arch Volume: 469(6) Pages: 687-696
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Protein Expression Profiling of Giant Cell Tumors of Bone Treated with Denosumab. (2016)
  • Author(s): Mukaihara K, Suehara Y, Kohsaka S, Akaike K, Tanabe Y, Kubota D, Ishii M, Fujimura T, Kazuno S, Okubo T, Takagi T, Yao T, Kaneko K, Saito T.
  • Journal Title: PLoS One Volume: 10 Issue: 2 Pages: e0148401-e0148401
  • DOI: 10.1371/journal.pone.0148401
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Skeletal metastasis of unknown primary origin at the initial visit: A retrospective analysis of 286 cases. (2015)
  • Author(s): Takagi T, Katagiri H, Kim Y, Suehara Y, Kubota D, Akaike K, Ishii M, Mukaihara K, Okubo T, Murata H, Takahashi M, Kaneko K , Saito T.
  • Journal Title: ＰＬＯＳ Ｏｎｅ Volume: ..
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 原発不明癌骨転移の臨床的検討 (2014)
  • Author(s): 赤池 慶祐、末原 義之、金 栄智、片桐 浩久、高橋 満、齋藤 剛、金子 和夫、高木 辰哉
  • Organizer: 第87回日本整形外科学会学術総会
  • Place of Presentation: 神戸
  • Year and Date: 2014-05-22 – 2014-05-25
• [Presentation] 肺腺癌ではGalectin-4とTTF-1の発現は逆相関する (2014)
  • Author(s): 原貴恵子、齋藤剛、林大久生、三谷恵子、八尾隆史
  • Organizer: 第103回日本病理学会総会
  • Place of Presentation: 広島
  • Year and Date: 2014-04-28 – 2014-04-30