Analysis of cancer associated microenvironment in colorectal liver metastasis and application of histopathological asessment

• Project/Area Number: 16K08655
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Iwate Medical University
• Principal Investigator: ISHIDA KAZUYUKI 岩手医科大学, 医学部, 准教授 (40444004)
• Co-Investigator(Kenkyū-buntansha): 菅井 有 岩手医科大学, 医学部, 教授 (20187628)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 大腸癌肝転移 / 術前化学療法 / 病理診断 / 癌関連線維芽細胞 / 画像診断 / 組織所見 / 画像所見 / 大腸癌転移 / がん間質 / 病理学

Outline of Final Research Achievements

(1) We showed histological findings for every representative chemotherapy regimen including molecular target drug for colorectal liver metastases (CRLM) to clarify the effects of preoperative chemotherapy.
(2) The immunohistological expression status of cancer-associated fibroblasts was lower in metastases of lymph node and liver than in primary colorectal lesions. In addition, there was no difference in immunohistological expression status between CRLM with chemotherapy group and without chemotherapy group.
(3) Morphologic appearance of CRLM after preoperative chemotherapy on contrast-enhanced CT scans was correlated with detailed histologic findings and the histologic tumor response regarding necrosis.

Academic Significance and Societal Importance of the Research Achievements

大腸癌肝転移の治療の主体は手術療法であり，切除された肝転移巣に対する病理学的評価は予後を予測する因子となることが報告されている．近年では肝転移巣の切除前に化学療法を行う機会が増加しており，今回の研究により，術前化学療法（分子標的治療薬を含む）を行った際の組織学的評価方法が確立された．さらに，大腸癌の原発巣と転移巣の違い，術前化学療法の有無による癌関連線維芽細胞の発現状態が明らかになった．加えて，詳細な組織学的所見に基づいて画像診断に反映されている所見を明らかにしたことで，更なる画像診断の精度向上，予後の推測に寄与するものと考えられた．

Research Products

• [Journal Article] Expression of Epithelial-Mesenchymal Transition Proteins in Pancreatic Anaplastic (Undifferentiated) Carcinoma. (2019)
  • Author(s): Ishida K, Yamashita R, Osakabe M, Uesugi N, Yamada N, Nitta H, Fujishima F, Motoi F, Suzuki H, Shimamura H, Noda Y, Sawai T, Unno M, Sasano H, Sasaki A, Sugai T.
  • Journal Title: Pancreas. Volume: 48 Issue: 1 Pages: 36-42
  • DOI: 10.1097/mpa.0000000000001199
  • Peer Reviewed / Open Access
• [Journal Article] Immunohistochemical analysis of the epithelial to mesenchymal transition in uterine carcinosarcoma. (2019)
  • Author(s): Osakabe M, Fukagawa D, Sato C, Sugimoto R, Uesugi N, Ishida K, Itamochi H, Sugiyama T, Sugai T.
  • Journal Title: Int J Gynecol Cancer. Volume: 印刷中 Issue: 2 Pages: 277-281
  • DOI: 10.1136/ijgc-2018-000038
  • Peer Reviewed / Open Access
• [Journal Article] An extremely rare case who underwent total remnant pancreatectomy due to recurrent pancreatic metastasis of intraductal tubulopapillary neoplasm. (2019)
  • Author(s): Umemura A, Ishida K, Nitta H, Takahara T, Hasegawa Y, Makabe K, Sugai T, Sasaki A.
  • Journal Title: Clin J Gastroenterol. Volume: 12 Issue: 2 Pages: 153-159
  • DOI: 10.1007/s12328-018-0913-x
  • Peer Reviewed / Open Access
• [Journal Article] Budd-Chiari Syndrome and Esophageal Achalasia: Unrecognized Intrahepatic Cholangiocarcinoma Invading Multiple Organs (2018)
  • Author(s): Kakisaka K, Endo K, Sugimoto R, Ishida K, Sugai T, Takikawa Y.
  • Journal Title: Internal Medicine Volume: 57 Issue: 15 Pages: 2197-2201
  • DOI: 10.2169/internalmedicine.0448-17
  • NAID: 130007428820
  • ISSN: 0918-2918, 1349-7235
  • Year and Date: 2018-08-01
  • Peer Reviewed / Open Access
• [Journal Article] Hepatic Angiomyolipoma Staining in the Post-vascular Phase of Contrast-enhanced Ultrasound Due to the Presence of Macrophages (2018)
  • Author(s): Endo K, Kuroda H, Kakisaka K, Oikawa T, Sawara K, Ishida K, Sugai T, Takikawa Y.
  • Journal Title: Internal Medicine Volume: 57 Issue: 9 Pages: 1247-1251
  • DOI: 10.2169/internalmedicine.9697-17
  • NAID: 130006730690
  • ISSN: 0918-2918, 1349-7235
  • Year and Date: 2018-05-01
  • Peer Reviewed / Open Access
• [Journal Article] Correlation between CT morphologic appearance and histologic findings in colorectal liver metastasis after preoperative chemotherapy. (2018)
  • Author(s): Ishida K, Tamura A, Kato K, Uesugi N, Osakabe M, Eizuka M, Hasegawa Y, Nitta H, Otsuka K, Sasaki A, Ehara S, Sugai T.
  • Journal Title: Abdom Radiol (NY). Volume: 43 Issue: 11 Pages: 2991-3000
  • DOI: 10.1007/s00261-018-1588-y
  • NAID: 120006644553
  • Peer Reviewed / Open Access
• [Journal Article] Analysis of cancer-associated fibroblasts and the epithelial-mesenchymal transition in cutaneous basal cell carcinoma, squamous cell carcinoma and malignant melanoma (2018)
  • Author(s): Sasaki K, Sugai T, Ishida K, Osakabe M, Amano H, Kimura H, Sakuraba M, Kashiwa K, Kobayashi S
  • Journal Title: Hum Pathol Volume: - Pages: 1-8
  • DOI: 10.1016/j.humpath.2018.03.006
  • Peer Reviewed / Open Access
• [Journal Article] Molecular Profiling Based on KRAS/BRAF Mutation, Methylation, and Microsatellite Statuses in Serrated Lesions. (2018)
  • Author(s): Sugai T, Eizuka M, Fujita Y, Kawasaki K, Yamamoto E, Ishida K, Yamano H, Suzuki H, Matsumoto T.
  • Journal Title: Dig Dis Sci. Volume: 63 Issue: 10 Pages: 2626-2638
  • DOI: 10.1007/s10620-018-5167-4
  • Peer Reviewed / Open Access
• [Journal Article] Same-Day Preventive Embolization and Surgical Excision?of Carotid Body Tumor (2018)
  • Author(s): Tamura Akio、Nakasato Tatsuhiko、Izumisawa Mitsuru、Nakayama Manabu、Ishida Kazuyuki、Shiga Kiyoto、Ehara Shigeru
  • Journal Title: CardioVascular and Interventional Radiology Volume: 41 Issue: 6 Pages: 979-982
  • DOI: 10.1007/s00270-018-1894-3
  • Peer Reviewed / Open Access
• [Journal Article] Evaluation of ballooned hepatocytes as a risk factor for future progression of fibrosis in patients with non-alcoholic fatty liver disease (2018)
  • Author(s): Kakisaka Keisuke、Suzuki Yuji、Fujiwara Yudai、Abe Tamami、Yonezawa Miki、Kuroda Hidekatsu、Ishida Kazuyuki、Sugai Tamotsu、Takikawa Yasuhiro
  • Journal Title: Journal of Gastroenterology Volume: NA Issue: 12 Pages: 1285-1291
  • DOI: 10.1007/s00535-018-1468-9
  • Peer Reviewed / Open Access
• [Journal Article] The B-Mode Image-Guided Ultrasound Attenuation Parameter Accurately Detects Hepatic Steatosis in Chronic Liver Disease. (2018)
  • Author(s): Fujiwara Y, Kuroda H, Abe T, Ishida K, Oguri T, Noguchi S, Sugai T, Kamiyama N, Takikawa Y.
  • Journal Title: Ultrasound Med Biol. Volume: 44 Issue: 11 Pages: 2223-2232
  • DOI: 10.1016/j.ultrasmedbio.2018.06.017
  • Peer Reviewed / Open Access
• [Journal Article] Association between contrast-enhanced ultrasonography and histopathological findings of the metastatic lymph nodes of patients with head and neck cancer: A preliminary study. (2018)
  • Author(s): Oikawa SI, Shiga K, Saito D, Katagiri K, Ikeda A, Tuchida K, Miyaguchi J, Ishida K, Sugai T.
  • Journal Title: Oncol Lett. Volume: 15 Pages: 4171-4176
  • DOI: 10.3892/ol.2018.7835
  • Peer Reviewed / Open Access
• [Journal Article] Clinicopathological and molecular stability and methylation analyses of gastric papillary adenocarcinoma (2017)
  • Author(s): Uesugi, N. Sugai, T. Sugimoto, R. Eizuka, M. Fujita, Y. Sato, A. Osakabe, M. Ishida, K. Koeda, K. Sasaki, A. Matsumoto, T.
  • Journal Title: Pathology Volume: 49 Issue: 6 Pages: 596-603
  • DOI: 10.1016/j.pathol.2017.07.004
  • Peer Reviewed
• [Journal Article] Expression of cell cycle-related proteins in oropharyngeal squamous cell carcinoma based on human papilloma virus status (2017)
  • Author(s): Tsuchida, K. Sugai, T. Uesugi, N. Ishida, K. Matsuura, K. Sato, I. Shiga, K. Sato, H.
  • Journal Title: Oncol Rep Volume: 38 Issue: 2 Pages: 908-916
  • DOI: 10.3892/or.2017.5720
  • Peer Reviewed / Open Access
• [Journal Article] Vascular Invasion and Stromal S100A4 Expression at the Invasive Front of Colorectal Cancer are Novel Determinants and Tumor Prognostic Markers (2017)
  • Author(s): Sugai, T. Yamada, N. Eizuka, M. Sugimoto, R. Uesugi, N. Osakabe, M. Ishida, K. Otsuka, K. Sasaki, A. Matsumoto, T.
  • Journal Title: J Cancer Volume: 8 Issue: 9 Pages: 1552-1561
  • DOI: 10.7150/jca.18685
  • Peer Reviewed / Open Access
• [Journal Article] Analysis of molecular alterations in laterally spreading tumors of the colorectum. (2017)
  • Author(s): Sugai T, Habano W, Takagi R, Yamano H, Eizuka M, Arakawa N, Takahashi Y, Yamamoto E, Kawasaki K, Yanai S, Ishida K, Suzuki H, Matsumoto T.
  • Journal Title: J Gastroenterol Volume: 52 Issue: 6 Pages: 715-723
  • DOI: 10.1007/s00535-016-1269-y
  • NAID: 110006550042
  • Peer Reviewed / Open Access
• [Journal Article] Association between white opaque substance under magnifying colonoscopy and lipid droplets in colorectal epithelial neoplasms (2017)
  • Author(s): Kawasaki, K. Eizuka, M. Nakamura, S. Endo, M. Yanai, S. Akasaka, R. Toya, Y. Fujita, Y. Uesugi, N. Ishida, K. Sugai, T. Matsumoto, T.
  • Journal Title: World J Gastroenterol Volume: 23 Issue: 47 Pages: 8367-8375
  • DOI: 10.3748/wjg.v23.i47.8367
  • Peer Reviewed / Open Access
• [Journal Article] Analysis of PI3K mutations and PI3K pathway proteins in advanced gastric cancer (2017)
  • Author(s): Ito C, Nishizuka SS, Ishida K, Uesugi N, Sugai T, Tamura G, Koeda K, Sasaki A
  • Journal Title: Journal of Surgical Research Volume: 212 Pages: 195-204
  • DOI: 10.1016/j.jss.2017.01.018
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] 胆膵腫瘍に対する術前治療と切除前後の効果判定法．膵癌に対する術前治療後の病理組織学的効果判定法 (2017)
  • Author(s): 石田和之，菅井有
  • Journal Title: 胆と膵 Volume: 38 Pages: 459-463
• [Journal Article] 臨床医も知っておくべき免疫組織化学染色のすべて．転移性腫瘍と免疫組織化学染色 (2017)
  • Author(s): 菅井有，上杉憲幸，藤田泰子，杉本亮，佐藤綾香，永塚真，鈴木正通，刑部光正，石田和之
  • Journal Title: 胃と腸 Volume: 52 Pages: 1052-1066
• [Journal Article] 消化管組織病理入門講座(第19回)．胃分化型腺癌．乳頭腺癌，管状腺癌，再生との鑑別 (2017)
  • Author(s): 石田和之，永塚真，菅井有，鳥谷洋右，松本主之
  • Journal Title: 胃と腸 Volume: 52 Pages: 110-118
• [Journal Article] Tumor budding at the invasive front of colorectal cancer may not be associated with the epithelial-mesenchymal transition. (2017)
  • Author(s): Yamada N, Sugai T, Eizuka M, Tsuchida K, Sugimoto R, Mue Y, Suzuki M, Osakabe M, Uesugi N, Ishida K, Otsuka K, Matsumoto T.
  • Journal Title: Hum Pathol. Volume: 60 Pages: 151-159
  • DOI: 10.1016/j.humpath.2016.10.007
  • Peer Reviewed / Open Access
• [Journal Article] Molecular differences in the microsatellite stable phenotype between left-sided and right-sided colorectal cancer. (2016)
  • Author(s): Takahashi Y, Sugai T, Habano W, Ishida K, Eizuka M, Otsuka K, Sasaki A, Matsumoto T, Morikawa T, Unno M, Suzuki H.
  • Journal Title: Int J Cancer Volume: 139 Issue: 11 Pages: 2493-2501
  • DOI: 10.1002/ijc.30377
  • Peer Reviewed / Open Access
• [Journal Article] Visualizing the hepatic vascular architecture using superb microvascular imaging in patients with hepatitis C virus: A novel technique. (2016)
  • Author(s): Kuroda H, Abe T, Kakisaka K, Fujiwara Y, Yoshida Y, Miyasaka A, Ishida K, Ishida H, Sugai T, Takikawa Y.
  • Journal Title: World J Gastroenterol. Volume: 22 Issue: 26 Pages: 6057-6064
  • DOI: 10.3748/wjg.v22.i26.6057
  • Peer Reviewed / Open Access
• [Journal Article] Reversible sclerosing cholangitis with ulcerative colitis. (2016)
  • Author(s): Kakisaka K, Ishida K, Kataoka K, Suzuki Y, Yanai S, Kuroda H, Sugai T, Matsumoto T, Takikawa Y
  • Journal Title: Pathol Int. Volume: 66 Issue: 7 Pages: 404-408
  • DOI: 10.1111/pin.12427
  • NAID: 120006666415
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Immunohistochemical analysis of steroidogenic enzymes in ovarian-type stroma of pancreatic mucinous cystic neoplasms: Comparative study of subepithelial stromal cells in intraductal papillary mucinous neoplasms of the pancreas. (2016)
  • Author(s): Ishida K, Sasano H, Moriya T, Takahashi Y, Sugimoto R, Mue Y, Murakami K, Fujishima F, Nakamura Y, Morikawa T, Motoi F, Suzuki T, Unno M, Sugai T.
  • Journal Title: Pathol Int. Volume: 66 Issue: 5 Pages: 281-287
  • DOI: 10.1111/pin.12406
  • NAID: 120006644555
  • Peer Reviewed / Open Access
• [Presentation] Correlation between CT morphologic appearance and histologic findings in colorectal liver metastasis with preoperative chemotherapy (2017)
  • Author(s): Ishida K
  • Organizer: 2nd Eastern and Western Association Liver Tumors (EWALT)
  • Int'l Joint Research / Invited
• [Presentation] リンパ節の超音波像に影響を与える病理像 (2017)
  • Author(s): 石田和之
  • Organizer: 第39回日本乳腺甲状腺超音波医学会学術集会
  • Invited
• [Presentation] 超音波診断に役立つ甲状腺乳頭癌リンパ節転移の病理像 (2017)
  • Author(s): 石田和之
  • Organizer: 第39回日本乳腺甲状腺超音波医学会学術集会
  • Invited
• [Presentation] 腹腔鏡下スリーブ状胃切除時の肝生検組織でみられるindeterminate NASHの臨床病理学的特徴 (2017)
  • Author(s): 石田和之，佐々木章，柿坂啓介，馬場誠朗，藤原裕大，阿部珠美，杉本亮，藤田泰子，刑部光正，上杉憲幸，黒田英克，菅井有
  • Organizer: 第35回日本肥満症治療学会学術集会
• [Presentation] Immunohistochemical analysis of tumor histogenesis in pancreatic (anaplastic) carcinoma (2017)
  • Author(s): 石田和之，山下莉奈，山田範幸，刑部光正，上杉憲幸，藤島史喜，鈴木博義，野田裕，澤井高志，菅井有
  • Organizer: 第107回日本病理学会総会
• [Presentation] 空腸部分切除を施行した一例 (2017)
  • Author(s): 石田和之，佐藤綾香，深川大輔，佐々木孝輔，深川智之，土田宏大，永塚真，高橋弥生，鈴木正通，杉本亮，無江良晴，刑部光正，上杉憲幸，佐藤直夫，坂本隆，菅井有
  • Organizer: 第84回日本病理学会東北支部学術集会
• [Presentation] 化学療法後の大腸癌肝転移巣におけるCT所見と病理所見との対比 (2016)
  • Author(s): 石田 和之
  • Organizer: 第30回日本腹部放射線学会
  • Place of Presentation: 金沢
  • Year and Date: 2016-06-24
• [Presentation] 化学療法後の大腸癌肝転移巣におけるCT所見と病理所見との対比 (2016)
  • Author(s): 石田 和之
  • Organizer: 第105回日本病理学会総会
  • Place of Presentation: 仙台
  • Year and Date: 2016-05-12
• [Presentation] 臓器別病理診断講習会：膵腫瘍 (2016)
  • Author(s): 石田 和之
  • Organizer: 第105回日本病理学会総会
  • Place of Presentation: 仙台
  • Year and Date: 2016-05-12
  • Invited
• [Presentation] 発生部位別に基づいた大腸MSS (Microsatellite stable) 型癌の臨床病理学的及び分子病理学的特徴の解析 (2016)
  • Author(s): 高橋 弥生，石田 和之，菅井 有，他
  • Organizer: 第105回日本病理学会総会
  • Place of Presentation: 仙台
  • Year and Date: 2016-05-12
• [Presentation] 大腸癌原発巣とリンパ節転移巣におけるがん間質の免疫組織学的検討 (2016)
  • Author(s): 熊谷 優里，高橋 弥生，石田 和之，菅井 有，他
  • Organizer: 第105回日本病理学会総会
  • Place of Presentation: 仙台
  • Year and Date: 2016-05-12