Fibroblast growth factor receptor 2 is associated with poor overall survival in clear cell carcinoma of the ovary and may be a novel therapeutic approach

• Project/Area Number: 24592517
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Tottori University
• Principal Investigator: ITAMOCHI Hiroaki 鳥取大学, 医学部, 准教授 (20314601)
• Co-Investigator(Kenkyū-buntansha): SATO Syinya 鳥取大学, 医学部附属病院, 助教 (10423261) ; SATO Seiya 鳥取大学, 医学部附属病院, 助教 (30621007) ; HARADA Tasuku 鳥取大学, 医学部, 教授 (40218649) ; SHIMADA Muneaki 鳥取大学, 医学部, 講師 (40362892) ; CHIKUMI Jun 鳥取大学, 医学部附属病院, 医員 (70467702) ; OISHI Tetsuro 鳥取大学, 医学部附属病院, 講師 (80359877) ; KIGAWA Junzo 鳥取大学, 医学部附属病院, 教授 (00177784)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
• Keywords: 卵巣明細胞腺癌 / FGFR2

Outline of Final Research Achievements

We previously found that gene and protein expression of FGFR2 were increased in ovarian clear cell carcinoma (CCC); here, we examined FGFR2 expression in CCC tumor tissues and its correlation with clinical parameters. We also analyzed the effect of an FGFR inhibitor on the growth of CCC cells to investigate whether FGFR2 could be a therapeutic target for this disease. The expressions of FGFR2 were found in 96%of CCC. The 5-year survival rate for patients with a moderate or strong expression of FGFR2 was significantly lower than that for those with an absent or poor expression of FGFR2 (54% vs 79%). Multivariable analysis revealed that FGFR2 expression was independent prognostic factors. The FGFR inhibitor effectively suppressed the growth of CCC cells with induction of G1 cell cycle arrest and down-regulated the expression of phosphorylated Akt and phosphorylated ERK. We conclude that FGFR2 is an important biomarker predictive of patient outcome and is a potential target for CCC.

Research Products

• [Journal Article] Loss of ARID1A expression is associated with poor prognosis in patients with stage I/II clear cell carcinoma of the ovary. (2015)
  • Author(s): Itamochi H, Oumi N, Oishi T, Shoji T, Fujiwara H, Sugiyama T, Suzuki M, Kigawa J, Harada T.
  • Journal Title: Int J Clin Oncol
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Fibroblast growth factor receptor 2 is associated with poor overall survival in clear cell carcinoma of the ovary and nay be a novel therapeutic approach. (2015)
  • Author(s): Itamochi H, Oumi N, Oishi T, Taniguchi F, Shoji T, Fujiwara H, Sugiyama T, Suzuki M, Kigawa J, Harada T.
  • Journal Title: Int J Gynecol Cancer Volume: 25 Issue: 4 Pages: 570-576
  • DOI: 10.1097/igc.0000000000000414
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Checkpoint kinase inhibitor AZD7762 overcomes cisplatin resistance in clear cell carcinoma of the ovary. (2014)
  • Author(s): Itamochi H, Nishimura M, Oumi N, Kato M, Oishi T, Shimada M, Sato S, Naniwa J, Sato S, Kudoh A, Kigawa J, Harada H.
  • Journal Title: Int J Gynecol Cancer Volume: 24 Issue: 1 Pages: 61-69
  • DOI: 10.1097/igc.0000000000000014
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Dual inhibition of phosphatidylinositol 3’-kinase and mammalian target of rapamycin using NVP-BEZ235 as a vovel therapeutic approach for mucinous adenocarcinoma of the ovary. (2014)
  • Author(s): Kudoh A, Oishi T, Itamochi H, Sato S, Naniwa J, Sato S, Shimada M, Kigawa J, Harada T.
  • Journal Title: Int J Gynecol Cancer Volume: 24 Issue: 3 Pages: 444-453
  • DOI: 10.1097/igc.0000000000000091
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Establishment and characterization of a novel ovarian clear cell adenocarcinoma cell line, TU-OC-1, with a mutation in the PIK3CA gene. (2013)
  • Author(s): Itamochi H., Kato M., Nishimura M., Oumi N., Oishi T., Shimada M., Sato S., Naniwa J., Sato S., Nonaka M., Kudoh A., Terakawa N., Kigawa J., and Harada T.
  • Journal Title: Human Cell Volume: 26 Issue: 3 Pages: 121-127
  • DOI: 10.1007/s13577-013-0062-y
  • Peer Reviewed
• [Presentation] Fibroblast growth factor receptor 2 is associated with poor overall survival in clear cell carcinoma of the ovary and may be a novel therapeutic approach. (2015)
  • Author(s): Itamochi H, Oumi N, Oishi T, Taniguchi F, Shoji T, Saga Y, Fujiwara H, Shimada M, Sugiyama T, Suzuki M, Kigawa J, Harada T.
  • Organizer: 106th Annual Meeting of the American Association for Cancer Research
  • Place of Presentation: フィラデルフィア（アメリカ合衆国）
  • Year and Date: 2015-04-21
• [Presentation] 卵巣明細胞腺癌に対する線維芽細胞増殖因子受容体（FGFR）2シグナル伝達経路を標的とした新規治療戦略 難治性卵巣癌の克服を目指して. (2014)
  • Author(s): 板持広明
  • Organizer: 第66回日本産科婦人科学会学術講演会 シンポジウム
  • Place of Presentation: 東京国際フォーラム（東京都）
  • Year and Date: 2014-04-19
• [Presentation] 卵巣明細胞腺癌に対する線維芽細胞増殖因子受容体（FGFR）2 シグナル伝達経路を標的とした新規治療戦略
  • Author(s): 板持広明
  • Organizer: 日本産科婦人科学会学術講演会 シンポジウム
  • Place of Presentation: 東京国際フォーラム