Birt-Hogg-Dube syndrome: Molecular analysis and diagnosis of related lesions

• Project/Area Number: 24590408
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Chiba University
• Principal Investigator: NAKATANI Yukio 千葉大学, 医学(系)研究科(研究院), 教授 (20137037)
• Co-Investigator(Kenkyū-buntansha): FURUYA Mitsuko 横浜市立大学, 医学研究科, 准教授 (10361445) ; NAGASHIMA Yoji 東京女子医科大学, 附属病院, 教授 (10217995) ; OHTA Satoshi 千葉大学, 医学部附属病院, 准教授 (90324342)
• Co-Investigator(Renkei-kenkyūsha): YAMAGUCHI Atsushi 千葉大学, 大学院医学研究院, 准教授 (00314336) ; HIROSHIMA Kenzo 東京女子医科大学, 八千代医療センター, 教授 (80218833)
• 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: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: フォリキュリン / バート・ホッグ・デュベ症候群 / 腎腫瘍 / 肺嚢胞 / 病理組織学 / 腎癌 / 気胸 / 遺伝子変異 / バート・ホッグ・デューベ症候群 / 病理学 / 遺伝子 / Birt-HoggｰDube症候群 / 国際情報交換 / 台湾

Outline of Final Research Achievements

Birt-Hogg-Dube syndrome (BHDS) is an autosomal dominant inherited disorder associated with a germline mutation of the folliculin gene (FLCN), characterized by fibrofolliculomas, renal tumors, pulmonary cysts and pneumothorax. The number of BHDS individuals is not studied in Japan. We have diagnosed 100 BHDS families by genetic testing. Pulmonary cysts in BHDS are bilateral and multifocal. Individuals with BHDS have a high risk of developing spontaneous, recurrent pneumothorax. Although BHD pulmonary cysts are frequently misdiagnosed as nonspecific cystic diseases, they are distinctly different in histopathology from other bullous changes. Renal tumors in BHDS showed overexpression of glycoprotein non-metastatic B (GPNMB) and underexpression of FLCN, whereas sporadic tumors showed inverted patterns. The distinctive expression patterns of GPNMB and FLCN might identify patients with renal tumors who need further work-up for BHDS.

Research Products

• [Journal Article] Distinctive expression patterns of GPNMB and folliculin in renal tumors in patients with Birt-Hogg-Dube syndrome. (2015)
  • Author(s): Furuya M, Hong SB, Tanaka R, Kuroda N, Nagashima Y, Nagahama K, Suyama T, Yao M, Nakatani Y
  • Journal Title: Cancer Sci Volume: 106 Pages: 315-323
  • DOI: 10.1111/cas.12601
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Immunohistochemical characterization of renal tumors in patients with Birt-Hogg-Dube syndrome. (2015)
  • Author(s): Iribe Y, Kuroda N, Nagashima Y, Yao M, Tanaka R, Gotoda H, Kawakami F, Imamura Y, Nakamura Y, Ando M, Araki A, Matsushima J, Nakatani Y, Furuya M
  • Journal Title: Pathol Int Volume: 65 Pages: 126-132
  • DOI: 10.1111/pin.12254
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Case of bilateral and multifocal renal cell carcinoma associated with Birt-Hogg-Dube syndrome (2015)
  • Author(s): Yamada Y, Sakamoto S, Furuya M, Nihei N, Nakatani Y, Ichikawa T
  • Journal Title: Int J Urol Volume: 22 Pages: 230-231
  • DOI: 10.1111/iju.12649
  • Peer Reviewed
• [Journal Article] Review of Renal Tumors associated with Birt-Hogg-Dube syndrome with focus on clinical and pathobiological aspects (2014)
  • Author(s): Kuroda N, Furuya M, Nagashima Y, Gotoda H, Kawakami F, Moritani S, Ota S, Hora M, Michal M, Hes O, Nakatani Y
  • Journal Title: Pol J Pathol Volume: 66 Pages: 93-99
  • Peer Reviewed
• [Journal Article] Intratumoral peripheral small papillary tuft (ITPSPT): A diagnostic clue of renal tumors associated with Birt-Hogg-Dubé syndrome. (2014)
  • Author(s): Kuroda N, Furuya M, Nagashima Y, Gotoda H, Moritani S, Kawakami F, Imamura Y, Bando Y, Takahashi M, Kanayama H, Ota S, Michal M, Hes O, Nakatani Y.
  • Journal Title: Ann Diagn Pathol Volume: vol18 Pages: 171-176
  • DOI: 10.1016/j.anndiagpath.2014.03.002
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Birt-Hogg-Dube syndrome: clinicopathological features of the lung. (2013)
  • Author(s): Furuya M, Nakatani Y
  • Journal Title: J Clin Pathol Volume: vol 66 Pages: 178-186
  • DOI: 10.1136/jclinpath-2012-201200
  • Peer Reviewed
• [Journal Article] Multifocal and microscopic chromophobe renal cell carcinomatous lesions associated with"capsulomas"without FCLN gene abnormality (2013)
  • Author(s): Sugimoto K, Takasawa A, Ichimiya S, Murata M, Kimura H, Aoyama T, Gille JJ, Kuroda N, Shimizu H, Hasegawa T, Sawada N, Furuya M, Nagashima Y.
  • Journal Title: Pathol Int Volume: 60 Pages: 510-5
  • DOI: 10.1111/pin.12099
  • Peer Reviewed
• [Journal Article] Unique mutation, accelerated mTOR signaling and angiogenesis in the pulmonary cysts of Birt-Hogg-Dubé syndrome. (2013)
  • Author(s): Nishii T, Tanabe M, Tanaka R, Matsuzawa T, Okudela K, Nozawa A, Nakatani Y, Furuya M
  • Journal Title: Pathol Int Volume: vol 63 Pages: 45-55
  • DOI: 10.1111/pin.12028
  • Peer Reviewed
• [Journal Article] Identification of miR-30d as a novel prognostic maker of prostate cancer (2012)
  • Author(s): Furuya Mitsuko
  • Journal Title: Oncotarget Volume: 36 Pages: 589-600
  • DOI: 10.1097/pas.0b013e3182475240
  • Peer Reviewed
• [Journal Article] FLCN gene-mutated renal cell neoplasms : mother and daughter cases with a novel germline mutation (2012)
  • Author(s): Nagashima Y, Furuya M, Gotohda H, Takagi S, Hes O, Michal M, Grossmann P, Tanaka R, Nakatani Y, Kuroda N
  • Journal Title: International Journal of Urology Volume: 19(5) Pages: 468-470
  • DOI: 10.1111/j.1442-2042.2011.02945.x
  • NAID: 10030755007
  • Peer Reviewed
• [Presentation] 本邦のBirt-Hogg-Dube 症候群62 家系における腎癌およびその他 の悪性腫瘍発症率と病理像の検討 (2014)
  • Author(s): 中谷行雄、長嶋洋治、矢尾正祐、松嶋惇、入部康弘、古屋 充子
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] Birt-Hogg-Dube症候群(BHDS)患者に発生した腎癌の1例 (2014)
  • Author(s): 松嶋 惇, 古屋 充子, 巣山 貴仁, 長嶋 洋治, 田中 玲子, 中谷 行雄
  • Organizer: 第45回腎癌研究会
  • Place of Presentation: 品川インターシティホール（東京都品川区）
  • Year and Date: 2014-07-20
• [Presentation] Birt-Hogg-Dube(BHD)症候群を背景に発症する腎癌例の疫学・臨床・病理学的検討 (2014)
  • Author(s): 古屋 充子, 田中 玲子, 黒田 直人, 長嶋 洋治, 矢尾 正祐, 中谷 行雄
  • Organizer: 第45回腎癌研究会
  • Place of Presentation: 品川インターシティホール（東京都品川区）
  • Year and Date: 2014-07-20
• [Presentation] Birt-Hogg-Dube(BHD)症候群における腎腫瘍の臨床病理学的検討 (2014)
  • Author(s): 古屋 充子, Hong Seung-Beom, 田中 玲子, 黒田 直人, 長嶋 洋治, 矢尾 正祐, 中谷 行雄
  • Organizer: 第103回日本病理学会総会
  • Place of Presentation: 広島国際会議場（広島県広島市）
  • Year and Date: 2014-04-24 – 2014-04-26
• [Presentation] Birt-Hogg-Dube症候群(BHDS)で腎ハイブリッド腫瘍および甲状腺癌を発生した1例の分子病理学的検討 (2014)
  • Author(s): 松嶋 惇, 古屋 充子, 長嶋 健, 巣山 貴仁, 長嶋 洋治, 太田 聡, 青木 一郎, 市川 智彦, 宮崎 勝, 黒田 直人, 田中 玲子, 中谷 行雄
  • Organizer: 第103回日本病理学会総会
  • Place of Presentation: 広島国際会議場（広島県広島市）
  • Year and Date: 2014-04-24 – 2014-04-26
• [Presentation] Birt-Hogg-Dube症候群随伴腎腫瘍の病理学的特徴 (2014)
  • Author(s): 黒田 直人(高知赤十字病院 病理診断科部), 古屋 充子, 長嶋 洋治, 後藤田 裕子, 森谷 鈴子, 川上 史, 今村 好章, 坂東 良美, 太田 聡, 中谷 行雄
  • Organizer: 第103回日本病理学会総会
  • Place of Presentation: 広島国際会議場（広島県広島市）
  • Year and Date: 2014-04-24 – 2014-04-26
• [Presentation] 気胸を呈する多発性肺嚢胞の臨床病理学的検討 Birt-Hogg-Dube症候群を中心に (2013)
  • Author(s): 古屋充子
  • Organizer: 第１０２回日本病理学会総会
  • Place of Presentation: 札幌
• [Presentation] A clinicopathologic study of 72 individuals in 33 Asian BHD families (2013)
  • Author(s): Furuya M
  • Organizer: Fifth BHD Symposium and Second HLRCC Symposium
  • Place of Presentation: Paris(France)
• [Presentation] Birt-Hogg-Dube症候群患者に発生した甲状腺濾胞癌の1例 (2013)
  • Author(s): 松嶋 淳
  • Organizer: 第５９回日本病理学会秋期特別集会
  • Place of Presentation: 甲府
• [Presentation] Novel mutation patterns and distinctive clinicopasthological features in Asian families with Birt- Hogg-Dube syndrome. (2013)
  • Author(s): Nakatani Y
  • Organizer: 第72回日本がん学会学術総会
  • Place of Presentation: 横浜
• [Presentation] Peculiar histopathological findings in lung lesions: Their Usefulness for Diagnosis and Research (2013)
  • Author(s): Nakatani Y
  • Organizer: The 8th Asia Pacific IAP Congress
  • Place of Presentation: Busan(Korea)
  • Invited
• [Presentation] Birt-Hogg-Dube症候群と確定した10家系における肺嚢胞の病理学的検討 (2012)
  • Author(s): 古屋充子
  • Organizer: 第101回日本病理学総会
  • Place of Presentation: 東京
• [Presentation] 新規遺伝子変異を示したBirt-Hogg-Dube症候群の１例 反復性気胸を伴う多発性肺嚢胞の分子病理学的検討 (2012)
  • Author(s): 西井鉄平
  • Organizer: 第101回日本病理学総会
  • Place of Presentation: 東京
• [Presentation] Birt-Hogg-Dube症候群における肺嚢胞の病理像：腎癌をもつBHDファミリーに対する病理診断の重要性 (2012)
  • Author(s): 中谷行雄
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
• [Remarks] Birt-Hogg-Dube 症候群情報ネット (BHD ネット)
  • URL: http://www.bhd-net.jp/
• [Remarks] バート・ホッグ・デュベ症候群ネット
  • URL: http://www.bhd-net.jp/
• [Remarks] Birt-Hogg-Dubé 症候群情報ネット (BHD ネット)
  • URL: http://www.bhd-net.jp/