Involvement of mismatch repair abnormalities in the malignant transformation of ovarian endometriosis

• Project/Area Number: 22791524
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Obstetrics and gynecology
• Research Institution: Shinshu University
• Principal Investigator: FUSEYA Chiho 信州大学, 医学部・附属病院, 助教(診療) (50447736)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 子宮内膜症 / 癌化 / ミスマッチ修復

Research Abstract

In this study, the mismatch repair(MMR) abnormalities in the carcinogenetic process of endometriosis were analyzed. The immunohistochemical expressions of mismatch repair proteins were step-wisely decreased in normal entopic endometrium, endometriosis, and ovarian carcinoma. Inversely, the step-wisely increasing frequencies of microsatellite instability in normal entopic endometrium, endometriosis, and ovarian carcinoma were observed. In addition, the down-regulations of MMR proteins were observed in cultured normal endometrial glandular cells under the condition with inflammatory cytokines(TNF-α, IL-6). These findings suggest that mismatch repair abnormalities, which are induced by inflammation, might be involved in the malignant transformation of ovarian endometriosis.

Research Products

• [Journal Article] Involvement of pelvic inflammation-related mismatch repair abnormalities and microsatellite instability in the malignant transformation of ovarian endometriosis (2012)
  • Author(s): Fuseya C, Horiuchi A, Hayashi A, Suzuki A, Miyamoto T, Hayashi T, Shiozawa T
  • Journal Title: Hum Pathol
  • Peer Reviewed
• [Journal Article] Hypoxia up regulates ovarian cancer invasiveness via the binding of HIF-1αto a hypoxia-induced, methylation-free hypoxia response element of S100A4 gene (2012)
  • Author(s): Horiuchi A, Hayashi T, Kikuchi N, Hayashi A, Fuseya C, Shiozawa T, Konishi I.
  • Journal Title: Int J Cancer Volume: 27 Issue: 8 Pages: 755-67
  • DOI: 10.1002/ijc.27448
  • Peer Reviewed
• [Journal Article] Involvement of pelvic inflammation-related mismatch repair abnormalities and microsatellite instability in the malignant transformation of ovarian endometriosis (2012)
  • Author(s): Fuseya C, Horiuchi A, et al
  • Journal Title: Human pathology Volume: (In press)
  • Peer Reviewed
• [Journal Article] Type-specific roles of histone deacetylase(HDAC) overexpression in ovarian carcinoma : HDAC1 enhances cell proliferation and HDAC3 stimulates cell migration with downregulation of E-cadherin (2010)
  • Author(s): Hayashi A, Horiuchi A, Kikuchi N, Hayashi T, Fuseya C, Suzuki A, Konishi I, Shiozawa T
  • Journal Title: Int J Cancer Volume: 127(6) Pages: 1332-46
  • Peer Reviewed
• [Presentation] 慢性炎症は卵巣子宮内膜症におけるmismatch repair(MMR)異常に関与する (2011)
  • Author(s): 布施谷千穂、堀内晶子、他
  • Organizer: 第63回日本産科婦人科学会学術講演会
  • Place of Presentation: 大阪
  • Year and Date: 2011-08-30
• [Presentation] LEGH(lobular endocervical grandula rhyperplasia)は悪性腺腫の前駆病変か? (2011)
  • Author(s): 高津亜希子、布施谷千穂、他
  • Organizer: 第63回日本産科婦人科学会学術講演会
  • Place of Presentation: 大阪
  • Year and Date: 2011-08-30
• [Presentation] 卵巣癌細胞におけるHistonedeacetylase(HDAC)阻害剤と抗癌剤の併用効果 (2011)
  • Author(s): 林晶子、堀内晶子、布施谷千穂, 他
  • Organizer: 第63回日本産科婦人科学会学術講演会
  • Place of Presentation: 大阪
  • Year and Date: 2011-08-30
• [Presentation] 慢性炎症は卵巣子宮内膜症におけるmismatch repair (MMR)異常に関与する (2011)
  • Author(s): 布施谷千穂, 堀内晶子, 他
  • Organizer: 第63回日本産科婦人科学会学術講演会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2011-08-30
• [Presentation] LEGH (lobular endocervical grandular hyperplasia)は悪性腺腫の前駆病変か? (2011)
  • Author(s): 高津亜希子, 布施谷千穂, 他
  • Organizer: 第63回日本産科婦人科学会学術講演会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2011-08-30
• [Presentation] 卵巣癌細胞におけるHistone deacetylase (HDAC)阻害剤と抗癌剤の併用効果 (2011)
  • Author(s): 林晶子, 堀内晶子, 布施谷千穂, 他
  • Organizer: 第63回日本産科婦人科学会学術講演会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2011-08-30
• [Presentation] 卵巣子宮内膜症の癌化におけるミスマッチ修復機構異常の関与 (2010)
  • Author(s): 布施谷千穂、堀内晶子、他
  • Organizer: 第9回日本婦人科がん分子標的研究会学術集会
  • Place of Presentation: 大津
  • Year and Date: 2010-09-10
• [Presentation] Involvement of mismatch repair(MMR) abnormality in the malignant transformation of ovarian endometriosis (2010)
  • Author(s): Fuseya C, Horiuchi A, 他
  • Organizer: International Gynecologic Cancer Society(IGCS2010)
  • Place of Presentation: Praha
• [Presentation] 卵巣子宮内膜症の癌化におけるmismatch repair(MMR)異常の関与 (2010)
  • Author(s): 布施谷千穂、堀内晶子、他
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
• [Presentation] 慢性炎症は卵巣子宮内膜症におけるmismatch repair(MMR)異常に関与する (2010)
  • Author(s): 布施谷千穂、堀内晶子、他
  • Organizer: 生殖医学フォーラム
  • Place of Presentation: 佐賀
• [Presentation] 卵巣子宮内膜症におけるmismatch repair(MMR)異常の関与 (2010)
  • Author(s): 布施谷千穂、堀内晶子、他
  • Organizer: 第62回日本産科婦人科学会学術講演会
  • Place of Presentation: 東京
• [Presentation] 卵巣子宮内膜症におけるmismatch repair(MMR)異常の関与 (2010)
  • Author(s): 布施谷千穂、堀内晶子、林晶子、菊地範彦、鈴木昭久、高津亜希子、長田亮介、塩沢丹里
  • Organizer: 第62回日本産科婦人科学会総会・学術講演会
  • Place of Presentation: 東京
• [Presentation] 慢性炎症は卵巣子宮内膜症におけるmismatch repair(MMR)異常に関与する (2010)
  • Author(s): 布施谷千穂、堀内晶子、林晶子、鈴木昭久、岡賢二、塩沢丹里
  • Organizer: 生殖フォーラム
  • Place of Presentation: 佐賀
• [Presentation] Involvement of mismatch repair(MMR) abnormality in the malignant transformation of ovarian endometriosis. (2010)
  • Author(s): Fuseya C, Horiuchi A, Kikuchi N, Suzuki A, Takatsu A, Osada R, Shiozawa T.
  • Organizer: International Gynecologic Cancer Society (IGCS2010)
  • Place of Presentation: Praha