大腸癌漿膜浸潤部の微小環境が転移を促進する機構の解明

2014 Fiscal Year Annual Research Report

• Project/Area Number: 24590458
• Research Institution: National Cancer Center Japan
• Principal Investigator: 小嶋 基寛 独立行政法人国立がん研究センター, 先端医療センター, ユニット長 (30338470)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 人体病理学 / 大腸癌 / 癌 / 漿膜浸潤 / 癌微小環境

Outline of Annual Research Achievements

前年度までに漿膜弾性板を越えた大腸癌の浸潤は予後と強く相関し、この所見を判定することは現状のステージ分類を改善し、術後の治療に影響を与えうる事を報告し (Kojima M et al. Am J Surg Pathol 2010 and 2014)、海外を含めて報告することで、国際的なコンセンサスを得つつある (Liang WY et al. Modern Pathol 2015)。さらに我々は漿膜弾性板を越えた大腸癌の浸潤により、線維化、腫瘍の budding、マクロファージの浸潤を伴う特殊な微小環境 (Cancer microenvironment formed by peritoneal invasion: CMPI)が形成され、漿膜由来の線維芽細胞 (SPF)がCMPIの形成及び腫瘍の進展に関わることを報告した (Kojima M, et al. PLoS ONE 2014)。本年度は 1: CMPIの形成と広がる過程を予測する目的で臨床病理学的検討を施行した。2: 前年度までにSPFが腫瘍の刺激により多彩な反応を示すことが判明したため、その中に腫瘍促進に働く分子が存在すると考え、SPFの網羅解析情報から悪性度マーカーを抽出する試みを施行した。
1: 腫瘍が漿膜弾性板を越えて、CMPIが形成され、広がるにつれて、漿膜弾性板が腫瘍側に引き寄せられることが判明した。患者の予後は漿膜弾性板を越えた際に悪くなるが、漿膜弾性板が腫瘍側に引き寄せられても変化がなかった。一方で漿膜弾性板が腫瘍側に引き寄せられると、腫瘍の硬度が増し、イレウス症状が出現する頻度が高くなることが判明した (Yokota M et al. Cancer Sci 2015)。
2: がん培養上清で刺激したSPFの分子発現情報を 公開されている大腸がん患者組織の網羅解析情報に導入して、SPFの分子発現の特徴で分類すると、SPFと類似した分子発現情報を有する患者の予後は悪いことが判明した。がん培養上清で刺激したSPFで上昇する分子と予後を解析した結果、新たに TAGLIN等複数の間質に発現する予後マーカーが検出された。今後これらの機能解析を行っていく予定としている。

Research Products

• [Journal Article] MicroRNA markers for the diagnosis of pancreatic and biliary-tract cancers. (2015)
  • Author(s): Kojima M, Sudo H, Kawauchi J, Takizawa S, Kondou S, Nobumasa H, Ochiai A.
  • Journal Title: PLoS One Volume: 10(2) Pages: e0118220
  • DOI: 10.1371/journal.pone.0118220.
  • Peer Reviewed / Open Access
• [Journal Article] A resected case of intraductal tubulopapillary neoplasm of the pancreas: report of a case. (2015)
  • Author(s): Kitaguchi K, Kato Y, Kojima M, Okubo S, Takahashi D, Okada R, Nakayama Y, Nishida Y, Gotohda N, Takahashi S, Konishi M.
  • Journal Title: Int Surg Volume: 100(2) Pages: 281-6
  • DOI: 10.9738/INTSURG-D-14-00172.1.
  • Peer Reviewed
• [Journal Article] Spread of tumor microenvironment contributes to colonic obstruction through subperitoneal fibroblast activation in colon cancer. (2015)
  • Author(s): Yokota M, Kojima M, Higuchi Y, Nishizawa Y, Kobayashi A, Ito M, Saito N, Ochiai A.
  • Journal Title: Cancer Sci Volume: in press Pages: in press
  • DOI: 10.1111/cas.12615.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Pancreatic perfusion data and post-pancreaticoduodenectomy outcomes. (2015)
  • Author(s): Sugimoto M, Takahashi S, Kobayashi T, Kojima M, Gotohda N, Satake M, Ochiai A, Konishi M.
  • Journal Title: J Surg Res. Volume: 194(2) Pages: 441-9
  • DOI: 10.1016/j.jss.2014.11.046.
  • Peer Reviewed
• [Journal Article] Blood and lymphatic vessel invasion in pT1 colorectal cancer. An international concordance study (2015)
  • Author(s): Motohiro Kojima, et al.
  • Journal Title: J Clin Pathol Volume: in press Pages: in press
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] パラフィンブロックの長期保存と採取試料の固定までの時間が与えるKi-67免疫染色、DNAとRNAへの影響. (2015)
  • Author(s): 4.佐藤正明、小嶋基寛、永妻晶子、中村優香、福田幸子、斉藤典男、落合淳志
  • Journal Title: 診断病理 Volume: 32(1) Pages: 12-17
  • Peer Reviewed
• [Journal Article] What is the nature of pancreatic consistency? Assessment of the elastic modulus of the pancreas and comparison with tactile sensation, histology, and occurrence of postoperative pancreatic fistula after pancreaticoduodenectomy. (2014)
  • Author(s): Sugimoto M, Takahashi S, Kojima M, Gotohda N, Kato Y, Kawano S, Ochiai A, Konishi M.
  • Journal Title: Surgery Volume: 156(5) Pages: 1204-11
  • DOI: 10.1016/j.surg.2014.05.015.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Tumor-size-based morphological features of metastatic lymph node tumors from primary lung adenocarcinoma. (2014)
  • Author(s): Yamada E, Ishii G, Aramaki N, Aokage K, Hishida T, Yoshida J, Kojima M, Nagai K, Ochiai A.
  • Journal Title: Pathol Int Volume: 64(12) Pages: 591-600
  • DOI: 10.1111/pin.12213.
  • Peer Reviewed
• [Journal Article] Long-term outcomes after intersphincteric resection for low-lying rectal cancer. (2014)
  • Author(s): Saito N, Ito M, Kobayashi A, Nishizawa Y, Kojima M, Nishizawa Y, Sugito M.
  • Journal Title: Ann Surg Oncol Volume: 21(11) Pages: 3608-15
  • DOI: 10.1245/s10434-014-3762-y.
  • Peer Reviewed
• [Journal Article] Hypoxia imaging endoscopy equipped with laser light source from preclinical live animal study to first-in-human subject research. (2014)
  • Author(s): Kaneko K, Yamaguchi H, Saito T, Yano T, Oono Y, Ikematsu H, Nomura S, Sato A, Kojima M, Esumi H, Ochiai A.
  • Journal Title: PLoS One Volume: 9(6) Pages: e99055
  • DOI: 10.1371/journal.pone.0099055.
  • Peer Reviewed / Open Access
• [Journal Article] Clinical impact of elastic laminal invasion in colon cancer: elastic laminal invasion-positive stage II colon cancer is a high-risk equivalent to stage III. (2014)
  • Author(s): Yokota M, Kojima M, Nomura S, Nishizawa Y, Kobayashi A, Ito M, Ochiai A, Saito N.
  • Journal Title: Dis Colon Rectum. Volume: 57(7) Pages: 830-8
  • DOI: 10.1097/DCR.0000000000000124.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Optimal fixation for total preanalytic phase evaluation in pathology laboratories: a comprehensive study including immunohistochemistry, DNA, and mRNA assays. (2014)
  • Author(s): Sato M, Kojima M, Nagatsuma AK, Nakamura Y, Saito N, Ochiai A.
  • Journal Title: Pathol Int Volume: 64(5) Pages: 209-16
  • DOI: 10.1111/pin.12164.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Prognostic impact of M2 macrophages at neural invasion in patients with invasive ductal carcinoma of the pancreas. (2014)
  • Author(s): Sugimoto M, Mitsunaga S, Yoshikawa K, Kato Y, Gotohda N, Takahashi S, Konishi M, Ikeda M, Kojima M, Ochiai A, Kaneko H.
  • Journal Title: Eur J Cancer Volume: 50(11) Pages: 1900-8
  • DOI: 10.1016/j.ejca.2014.04.010.
  • Peer Reviewed
• [Presentation] Correlation between the elastic modules of colorectal cancer tissue and clinicopathological and histological findings. (2015)
  • Author(s): Kawano S, Kojima M, Sugimoto S, Takahashi S, Saito N, Ochiai A.
  • Organizer: 104th Annual Meeting of USCAP 2015.
  • Place of Presentation: Boston, USA
  • Year and Date: 2015-03-21 – 2015-03-27
• [Presentation] Construction of an objective pathological diagnostic system of blood and lymphatic vessel invasion. (2015)
  • Author(s): Kojima M, et al.
  • Organizer: 104th Annual Meeting of USCAP 2015.
  • Place of Presentation: Boston, USA
  • Year and Date: 2015-03-21 – 2015-03-27
• [Presentation] 漿膜弾性板を越えて浸潤する大腸癌に生じる形態変化と形成される微小環境の解明 (2014)
  • Author(s): 小嶋基寛
  • Organizer: 第60回日本病理学会秋季特別総会
  • Place of Presentation: 沖縄
  • Year and Date: 2014-11-20 – 2014-11-21
• [Presentation] MicroRNA markers for the diagnosis of pancreatic and bile duct cancers. (2014)
  • Author(s): 7.Kojima M, Sudo H, Kawauchi J, Kondou S, Nobumasa H, Takizawa S, Ochiai A.
  • Organizer: 第73回日本癌学会学術総会 2014
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] Pathological diagnostic criterion of blood and lymphatic vessel invasion in colorectal cancer: a framework for developing an objective pathological diagnostic system using Delphi method, from the Pathology Working Group of the Japanese Society for Cancer of the Colon and Rectum. (2014)
  • Author(s): Kojima M, et al.
  • Organizer: 26th European Congress of Pathology
  • Place of Presentation: London, UK
  • Year and Date: 2014-08-30 – 2014-09-03
• [Presentation] 膵臓における腫瘍類似病変 腫瘍と鑑別を要する膵病変 overview (2014)
  • Author(s): 小嶋基寛 落合淳志
  • Organizer: 第103回日本病理学会総会
  • Place of Presentation: 広島
  • Year and Date: 2014-04-24 – 2014-04-26
• [Book] ガイドラインサポートハンドブック (2015)
  • Author(s): 小嶋基寛
  • Total Pages: 367
  • Publisher: 医薬ジャーナル社
• [Book] 日本臨床増刊号 最新臨床大腸癌学 (2015)
  • Author(s): 小嶋基寛
  • Total Pages: 714
  • Publisher: 日本臨床社
• [Book] 癌診療指針のための病理診断プラクティス 肝・胆・膵腫瘍 (2014)
  • Author(s): 小嶋基寛
  • Total Pages: 372
  • Publisher: 中山書店
• [Remarks] 小嶋 基寛
  • URL: http://www.ncc.go.jp/jp/ncce/rcio/research/clip/mokojima.html