Exploration of factors conferring increased malignancy on lung adenocarcinoma with micropapillary component

• Project/Area Number: 24590427
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Kitasato University
• Principal Investigator: JIANG Shi-Xu 北里大学, 医学部, 准教授 (70276153)
• Co-Investigator(Kenkyū-buntansha): NAGASHIO Ryo 北里大学, 医療衛生学部, 講師 (40618568)
• 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: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 肺癌 / 微小乳頭腺癌 / vimentin / 予後因子 / LCM / DNAマイクロアレイ発現解析 / 浸潤 / 転移

Outline of Final Research Achievements

Lung adenocarcinoma with micropapillary component (AC-MPC) is more malignant than conventional adenocarcinoma (CAC). On proteomics based on 2-DE, vimentin was 3.5-fold up-regulated in AC-MPC. Immunostaining in 101 AC-MPC and 119 CAC revealed that vimentin was expressed in 95 MPC and the expression scores were higher than those of well- and moderately differentiated CAC (P<0.0001), but not different from those of poorly differentiated CAC (P=0.561). Even within the AC-MPC entity, higher vimentin expression was correlated with more frequent vascular invasion and node metastasis (P<0.02), and multivariate analysis showed that high vimentin expression was an independent indicator of adverse prognosis (P<0.0053). In conclusion, vimentin expression is prevalent and up-regulated in MPC, which might reflect the biological essence of poorer differentiation or dedifferentiation, and have a role in the acquisition and increase of invasiveness and consequent more malignant nature of MPC.

Research Products

• [Journal Article] Prevalent and up-regulated vimentin expression in micropapillary components of lung adenocarcinomas and its adverse prognostic significance (2015)
  • Author(s): Nakashima H, Jiang SX, Sato Y, Hoshi K, Matsumoto T, Nagashio R, Kobayashi M, Matsuo Y, Shiomi K, Hayakawa K, Saegusa M, Satoh Y
  • Journal Title: Pathol Int Volume: 65 Issue: 4 Pages: 183-192
  • DOI: 10.1111/pin.12257
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Diagnostic and prognostic significances of MUC5B and TTF-1 expressions in resected non-small cell lung cancer. (2015)
  • Author(s): Nagashio R, Ueda J, Ryuge S, Nakashima H, Jiang SX, Kobayashi M, Yanagita K, Katono K, Satoh Y, Masuda N, Murakumo Y, Hachimura K, Sato Y.
  • Journal Title: Sci Rep Volume: 5 Issue: 1 Pages: 8649-8649
  • DOI: 10.1038/srep08649
  • Peer Reviewed / Open Access
• [Journal Article] Prognostic Significance of MYH9 Expression in Resected Non-Small Cell Lung Cancer (2015)
  • Author(s): Katono K, Sato Y, Jiang S-X, Kobayashi M, Nagashio R, Ryuge S, Fukuda E, Goshima N, Satoh Y, Saegusa M, Masuda N
  • Journal Title: PLoS ONE Volume: 10 Issue: 3 Pages: e0121460-e0121460
  • DOI: 10.1371/journal.pone.0121460
  • Peer Reviewed / Open Access
• [Journal Article] Acquisition of useful sero-diagnostic autoantibodies using the same patients' sera and tumor tissues. (2014)
  • Author(s): Kobayashi M, Nagashio R, Ryuge S, Murakami Y, Yanagita K, Nakashima H, Matsumoto T, Jiang SX, Saegusa M, Satoh Y, Masuda N, Sato Y
  • Journal Title: Biomed Res Volume: 35 Pages: 133-143
  • Peer Reviewed / Open Access
• [Journal Article] The clinicopathological significance of Lgr5 expression in lung adenocarcinoma. (2013)
  • Author(s): Ryuge S, Sato Y, Jiang SX, Wang G, Kobayashi M, Nagashio R, Katono K, Iyoda A, Satoh Y, Masuda N.
  • Journal Title: Lung Cancer Volume: 82 (1) Issue: 1 Pages: 134-138
  • DOI: 10.1016/j.lungcan.2013.06.010
  • Peer Reviewed
• [Journal Article] Tumor budding, myofibroblast proliferation, and fibrosis in obstructing colon carcinoma: the roles of Hsp47 and basic fibroblast growth factor (2013)
  • Author(s): Xu CJ, Mikami T, Nakamura T, Tsuruta T, Nakada N, Yanagisawa N, Jiang SX, Okayasu I
  • Journal Title: Pathology Research and Practice Volume: 209 Issue: 2 Pages: 69-74
  • DOI: 10.1016/j.prp.2012.10.008
  • Peer Reviewed
• [Journal Article] Prognostic impact of nestin in resected large cell neuroendocrine carcinoma of the lung. (2012)
  • Author(s): Ryuge S, Sato Y, Jiang Shi-X, Wang G, Matsumoto T, Katone K, Inoue H, Iyoda A, Satoh Y, Yoshimura H, Masuda N.
  • Journal Title: Lung Cancer Volume: 77(2) Issue: 2 Pages: 415-420
  • DOI: 10.1016/j.lungcan.2012.03.025
  • Peer Reviewed
• [Journal Article] CAXII is sero-diagnostic marker for lung cancer (2012)
  • Author(s): Kobayashi M, Matsumoto T, Sato Y, et al
  • Journal Title: PLoS ONE Volume: 7 (3) Issue: 3 Pages: e33952-e33952
  • DOI: 10.1371/journal.pone.0033952
  • Peer Reviewed
• [Journal Article] Anti-HuC and -HuD autoantibodies are differential sero-diagnostic markers for small cell carcinoma from large cell neuroendocrine carcinoma of the lung (2012)
  • Author(s): Matsumoto T, Jiang SX, et al
  • Journal Title: International Journal of Oncology Volume: 40 Pages: 1957-1962
  • DOI: 10.3892/ijo.2012.1405
  • Peer Reviewed
• [Presentation] Gene expressions in micropapillary component of lung cancer by microdissection-based DNA microarray (2015)
  • Author(s): 蒋 世旭、中島裕康、梅沢敦子、 長塩 亮、佐藤雄一、一戸昌明、早川和重、佐藤之俊、村雲芳樹
  • Organizer: 第104回日本病理学会総会
  • Place of Presentation: 名古屋国際会議場（愛知県・名古屋市）
  • Year and Date: 2015-04-30
• [Presentation] A CLINICOPATHOLOGICAL ANALYSIS OF PULMONARY ADENOCARCINOMA WITH MICROPAPILLARY COMPONENT (2013)
  • Author(s): Hiroyasu Nakashima, Shi-Xu Jiang, Masahito Naito, Fumihiro Ogawa, Yoshio Matsui, Kazu Shiomi, Akira Iyoda, Makoto Saegusa, Yukitoshi Satoh
  • Organizer: ASCVTS (Asian Society for Cardiovascular and Thoracic Surgery) 2013
  • Place of Presentation: Kobe
• [Presentation] 微乳頭成分を有する肺腺癌におけるタンパク発現の解析および臨床病理学的意義の検討
  • Author(s): 中島裕康、蒋 世旭、林 祥子、石井 大、 山﨑宏継、内藤雅仁、三窪将史、小川史洋、 塩見 和、佐藤雄一 、三枝 信、佐藤之俊
  • Organizer: 第103回日本病理学会総会
  • Place of Presentation: 広島国際会議場