Correlation analyses between 53BP1 expression and genomic instability in thyroid follicular tumors: significance as a molecular pathologic indicator

• Project/Area Number: 24590414
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Nagasaki University
• Principal Investigator: NAKASHIMA Masahiro 長崎大学, 原爆後障害医療研究所, 教授 (50284683)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 甲状腺濾胞性腫瘍 / 病理診断 / ゲノム不安定性 / 53BP1 / 蛍光免疫染色 / ゲノムコピー数異常 / アレイCGH / 甲状腺 / 濾胞性腫瘍 / DNA損傷応答 / 人体病理 / 分子病理診断 / 甲状腺朗報性腫瘍

Outline of Final Research Achievements

53BP1 belongs to DNA damage response (DDR) molecules and rapidly localizes at the site of DNA double strand breaks (DSB) forming nuclear foci (NF). The presence of 53BP1 NF can be an indicator of endogenous DSBs reflecting GIN. We have reported that type of 53BP1 NF by immunofluorescence (IF) is useful to estimate GIN in diverse tumorigenesis. This study aimed to clarify the type of 53BP1 NF in thyroid follicular tumor (FT). A total of 69 thyroid tissues, including follicular adenomas (FA), minimally invasive follicular carcinomas (MFC) and widely invasive FC (WFC), was annalyzed in this study. The type of 53BP1 expression was classified as low DDR and high DDR types. In results, the number of high DDR type of 53BP1 NF in tumor cells appeared to significantly increase with progression of carcinogenesis, such as FA-MFC-WFC. The type of 53BP1 expression by IF seems to reflect GIN to estimate malignant potency of FT. This method may be available in preoperative diagnosis for FT.

Research Products

• [Journal Article] Effect of age on the sensitivity of the rat thyroid gland to ionizing radiation. (2015)
  • Author(s): Matsuu-Matsuyama M, Shichijo K, Okaichi K, Kurashige T, Kondo H, Miura S, Nakashima M
  • Journal Title: J Radiation Research Volume: 56 Issue: 3 Pages: 1-9
  • DOI: 10.1093/jrr/rrv003
  • NAID: 120006987061
  • Peer Reviewed / Open Access
• [Journal Article] Clinicopathological characteristics of multiple primary cancers in hepatobiliary and pancreas malignancies (2015)
  • Author(s): Nanashima A, Nakashima M, et al
  • Journal Title: Anticancer Res Volume: 35 Pages: 1073-1078
  • Peer Reviewed
• [Journal Article] The common genetic variant rs944289 on chromosome 14q13.3 associates with risk of both malignant and benign thyroid tumors in the Japanese population. (2015)
  • Author(s): Rogounovitch TI, Bychkov A, Takahashi M, Mitsutake N, Nakashima M, Nikitski AV, Hayashi T, Hirokawa M, Ishigaki K, Shigematsu K, Bogdanova T, Matsuse M, Nishihara E, Minami S, Yamanouchi K, Ito M, Kawaguchi T, Kondo H, Takamura N, Ito Y, Miyauchi A, Matsuda F, Yamashita S, Saenko VA.
  • Journal Title: Thyroid Volume: 25 Issue: 3 Pages: 333-340
  • DOI: 10.1089/thy.2014.0431
  • NAID: 120006987147
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Involvement of hepatocyte growth factor-induced epithelial-mesenchymal transition in human adenomyosis (2015)
  • Author(s): Khan KN, Nakashima M, et al
  • Journal Title: Biol Reprod Volume: 92 Issue: 2 Pages: 35-35
  • DOI: 10.1095/biolreprod.114.124891
  • Peer Reviewed / Open Access
• [Journal Article] Low VHL mRNA expression is associated with more aggressive tumor features of papillary thyroid carcinoma (2015)
  • Author(s): Stanojevic B, Nakashima M, et al
  • Journal Title: PLoS One Volume: 9 Issue: 12 Pages: e114511-e114511
  • DOI: 10.1371/journal.pone.0114511
  • NAID: 120006986319
  • Peer Reviewed / Open Access
• [Journal Article] 17β-estradiol and lipopolysaccharide additively promote pelvic inflammation and growth of endometriosis (2015)
  • Author(s): Khan KN, Nakashima M, et al
  • Journal Title: Reprod Sci Volume: 22 Issue: 5 Pages: 585-594
  • DOI: 10.1177/1933719114556487
  • Peer Reviewed / Open Access
• [Journal Article] 原爆被爆者の放射線腫瘍病理 (2015)
  • Author(s): 中島正洋
  • Journal Title: 病理と臨床 Volume: 33 Pages: 17-22
• [Journal Article] Morphological difference in adult thyroid papillary carcinoma between Japan and Ukraine (2014)
  • Author(s): Ito M, Bogdanova T, Zurnadzhy L, Saenko V, Rogounovitch T, Mitsutake N, Kondo H, Maeda S, Nakashima M, Tronko M, Yamashita S.
  • Journal Title: Endocrine Journal Volume: 61 Issue: 12 Pages: 1221-1228
  • DOI: 10.1507/endocrj.EJ14-0239
  • NAID: 130004690931
  • ISSN: 0918-8959, 1348-4540
  • Peer Reviewed / Open Access
• [Journal Article] Intra-uterine microbial colonization and occurrence of endometritis in women with endometriosis† (2014)
  • Author(s): Khan KN, Nakashima M, et al
  • Journal Title: Hum Reprod Volume: 29 Issue: 11 Pages: 2446-2456
  • DOI: 10.1093/humrep/deu222
  • Peer Reviewed
• [Journal Article] Infliximab therapy for Crohn's-like disease in common variable immunodeficiency complicated by massive intestinal hemorrhage: a case report (2014)
  • Author(s): Akazawa Y, Nakashima M, et al
  • Journal Title: BMC Res Notes Volume: 22 Issue: 1 Pages: 382-382
  • DOI: 10.1186/1756-0500-7-382
  • Peer Reviewed
• [Journal Article] Radiation-associated small cell neuroendocrine carcinoma of the thyroid: a case report with molecular analyses (2014)
  • Author(s): Mussazhanova Z, Miura S, Stanojevic B, Rogounovitch T, Shiraishi T, Kurashige T, Shichijo K, Kaneko K, Takahashi H, Ito M, Nakashima M
  • Journal Title: Thyroid Volume: 24 Pages: 593-598
  • NAID: 120006986646
  • Peer Reviewed
• [Journal Article] Thyrotropin signaling confers more aggressive features with higher genomic instability on BRAFV600E-induced thyroid tumors in a mouse model (2014)
  • Author(s): Orim F, Bychkov A, Shimamura M, Nakashima M, Ito M, Matsuse M, Kurashige T, Suzuki K, Saenko V, Nagayama Y, Yamashita S, Mitsutake N
  • Journal Title: Thyroid Volume: 24 Pages: 502-510
  • NAID: 120006986647
  • Peer Reviewed
• [Journal Article] Significance of p53-binding protein 1 (53BP1) expression in thyroid papillary microcarcinoma: association with BRAFV600E mutation status (2013)
  • Author(s): Mussazhanova Z, Matsuda K, Naruke Y, Mitsutake N, Stanojevic B, Rougounovitch T, Saenko V, Suzuki K, Nishihara E, Hirokawa M, Ito M, Nakashima M
  • Journal Title: Histopathology Volume: 63 Pages: 726-734
  • Peer Reviewed
• [Journal Article] A predictive factor of the quality of microarray comparative genomic hybridization analysis for formalin-fixed paraffin-embedded archival tissue (2013)
  • Author(s): Nakao K, Oikawa M, Arai J, Mussazhanova Z, Kondo H, Shichijo K, Nakashima M, Hayashi T, Yoshiura K, Hatachi T, Nagayasu T
  • Journal Title: Diagnostic Molecular Pathology Volume: 22 Pages: 174-180
  • NAID: 120006986787
  • Peer Reviewed
• [Journal Article] ラット甲状腺濾胞上皮のDNA損傷応答と放射線誘導オートファジーに対する年齢の影響 (2012)
  • Author(s): 松山睦美、七絛和子、蔵重智美、三浦史郎、ムサジャノワ ジャンナ、中島正洋
  • Journal Title: 長崎医学会雑誌 Volume: 87 Pages: 269-272
• [Presentation] シンポジウム： がん登録法制化と病理情報システム「長崎県がん登録と被爆者腫瘍病理疫学」 (2014)
  • Author(s): 中島正洋
  • Organizer: 第６０回日本病理学会学秋期特別総会
  • Place of Presentation: 国立劇場おきなわ（沖縄）
  • Year and Date: 2014-11-21
• [Presentation] シンポジウム：甲状腺癌発生をその分子機構から考える「甲状腺がん幹細胞研究からみた甲状腺がん」 (2014)
  • Author(s): 中島正洋
  • Organizer: 第18回日本内分泌病理学会学術集会
  • Place of Presentation: 都道府県会館（東京）
  • Year and Date: 2014-11-01 – 2014-11-02
• [Presentation] Immunofluorescence analysis of P53-binding protein 1 (53BP1) in thyroid follicular tumors: possibility for preoperative diagnosis (2014)
  • Author(s): Otsubo R, Nakashima M, et al
  • Organizer: 26th European Congress of Pathology
  • Place of Presentation: ExCeL Centre, London, United Kingdom
  • Year and Date: 2014-08-30 – 2014-09-03
• [Presentation] 濾胞性腫瘍術前診断法としてのp53-binding protein 1（53BP1）蛍光免疫染色の意義 (2014)
  • Author(s): 大坪竜太、中島正洋、他
  • Organizer: 第2回日本甲状腺病理学会学術集会
  • Place of Presentation: 医療法人神甲会隈病院大会議室（神戸市）
  • Year and Date: 2014-07-12
• [Presentation] Immunofluorescence analysis of P53-binding protein 1 (53BP1) in thyroid follicular tumors: possibility for preoperative diagnosis (2014)
  • Author(s): Otsubo R, Nakashima M, et al
  • Organizer: 50th American Society Of Clinical Oncology annual meetin
  • Place of Presentation: McCormick Place, Chicago, USA
  • Year and Date: 2014-05-30 – 2014-06-03
• [Presentation] Storage of Biosamples from Atomic Bomb Survivors at Nagasaki University (2014)
  • Author(s): Nakashima M and Yamashita S
  • Organizer: RadiOmics Workshop
  • Place of Presentation: Tivoli Oriente Hotel, Lisbon, Portugal
  • Year and Date: 2014-04-30
• [Presentation] 原爆被爆者正常皮膚にみられる放射線晩発障害としてのゲノム不安定性解析 (2014)
  • Author(s): 三浦史郎、中島正洋、他
  • Organizer: 第103回 日本病理学会総会
  • Place of Presentation: 広島国際会議場（広島市）
  • Year and Date: 2014-04-24 – 2014-04-26
• [Presentation] 多臓器神経内分泌腫瘍における腫瘍抑制遺伝子PTENの分子異常 (2014)
  • Author(s): 松田勝也、中島正洋、他
  • Organizer: 第103回 日本病理学会総会
  • Place of Presentation: 広島国際会議場（広島市）
  • Year and Date: 2014-04-24 – 2014-04-26
• [Presentation] ラット甲状腺濾胞上皮の放射線応答に対する年齢影響 (2013)
  • Author(s): 松山睦美、七條和子、松田勝也、三浦史郎、関根一郎、中島正洋
  • Organizer: 第56回日本放射線影響学会
  • Place of Presentation: ホテルクラウンパレス青森（青森県青森市）
• [Presentation] 甲状腺濾胞性腫瘍術前診断法としてのp53-binding protein 1 (53BP1)蛍光免疫染色の意義 (2013)
  • Author(s): 大坪竜太、松田勝也、三浦史郎、松山睦美、七條和子、中島正洋
  • Organizer: 第17回日本内分泌病理学会学術総会
  • Place of Presentation: 関内新井ホール（神奈川県横浜市）
• [Presentation] チェルノブイリ成人の甲状腺乳頭癌と本邦症例との臨床病理学的検討 (2013)
  • Author(s): 伊東正博、Tatiana Bogdanova、黒濱大和、三原裕美、梅崎 靖、前田茂人、中島正洋、山下俊一
  • Organizer: 第102回日本病理学会
  • Place of Presentation: ロイトン札幌（北海道札幌市）
• [Presentation] シンポジウム2：「放射線とがん分子疫学」 原爆被爆者固形がん保存試料を用いた分子病理疫学研究 (2012)
  • Author(s): 中島正洋
  • Organizer: 第35回日本がん疫学・分子疫学研究会総会
  • Place of Presentation: 広島
  • Invited
• [Presentation] 原爆被爆者腫瘍組織バンクと分子病理学的研究の現状〈放射線病理学の現状と展望（ワークショップ）〉 (2012)
  • Author(s): 中島正洋、三浦史郎、及川将弘、吉浦孝一郎、蔵重智美、塚崎邦弘、松山睦美、七絛和子、松田勝也、鈴木啓司
  • Organizer: 第55回日本放射線影響学会
  • Place of Presentation: 仙台
• [Presentation] ラット甲状腺濾胞上皮の放射線誘発腫瘍に対する年齢影響とオートファジーの関与
  • Author(s): 松山睦美、徳永瑛子、蔵重智美、七條和子、松田勝也、三浦史郎、関根一郎、中島正洋
  • Organizer: 第54回原子爆弾後障害研究会
  • Place of Presentation: 広島国際会議場（広島県広島市）