Investigation for mechanism of onset of thymic epithelial tumors with special reference to possible viral involvement

• Project/Area Number: 17K10812
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory surgery
• Research Institution: Kansai Medical University
• Principal Investigator: MURAKAWA Tomohiro 関西医科大学, 医学部, 教授 (50359626)
• Co-Investigator(Kenkyū-buntansha): 齊藤 朋人 関西医科大学, 医学部, 講師 (10548605)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 縦隔外科 / 胸腺上皮性腫瘍 / 胸腺癌 / ウィルス / 網羅的遺伝子解析

Outline of Final Research Achievements

In this study, we tried to reveal mechanism of onset of thymic epithelial tumors with special reference to possible viral involvement using comprehensive mRNA expression profiling of 770 immune-related genes.
Contrary to our expectation, no direct involvement of viral infection could be detected. However, we found that PRAME (Preferentially expressed antigen in melanoma) was specifically expressed in thymic squamous cell carcinoma, whereas thymomas displayed negative expression or focal and weak expression.
These results identified PRAME as a novel diagnostic marker differentiating thymic squamous cell carcinoma from thymoma.

Academic Significance and Societal Importance of the Research Achievements

胸腺上皮性腫瘍の発症にウィルスが関与していることの証明は当初の期待とは異なり、本研究では直接的な証明はできなかった。
しかしながらPRAMEが胸腺癌特異的マーカーであり、免疫組織化学染色で既知の鑑別マーカーであるCD5やCD117と組み合わせることで胸腺癌のより正確な診断に有用であることが証明された。
胸腺癌と胸腺腫の鑑別診断は時に困難であることが知られており、PRAMEの免疫染色により鑑別診断制度を高め、ひいては治療選択に貢献できる可能性が本研究から示唆された。今後症例を蓄積しPRAMEのマーカーとしての有効性を検証していく必要がある。

Research Products

• [Journal Article] Utility of Geriatric Nutritional Risk Index in patients with lung cancer undergoing surgery. (2020)
  • Author(s): Hino H, Saito T, Matsui H, Taniguchi Y, Murakawa T.
  • Journal Title: European Journal of Cardio-Thoracic Surgery Volume: 57 Issue: 4 Pages: 775-782
  • DOI: 10.1093/ejcts/ezaa066
  • Peer Reviewed
• [Journal Article] Fine‐needle aspiration cytology of primary mediastinal synovial sarcoma: A case report with an immunocytochemical approach (2020)
  • Author(s): Yoshioka Saya、Ebisu Yusuke、Ishida Mitsuaki、Miyasaka Chika、Taniguchi Yohei、Murakawa Tomohiro、Tsuta Koji
  • Journal Title: Diagnostic Cytopathology Volume: 48 Issue: 5 Pages: 499-501
  • DOI: 10.1002/dc.24407
  • Peer Reviewed
• [Journal Article] Measurement of intrapleural pressure in patients with spontaneous pneumothorax: a pilot study (2019)
  • Author(s): Kaneda Hiroyuki、Nakano Takahito、Murakawa Tomohiro
  • Journal Title: BMC Pulmonary Medicine Volume: 19 Issue: 1
  • DOI: 10.1186/s12890-019-1038-9
  • Peer Reviewed
• [Journal Article] Preoperative biopsy does not affect postoperative outcomes of resectable non-small cell lung cancer. (2019)
  • Author(s): Taniguchi Y, Fukumoto K, Matsui H, Saito T, Murakawa T.
  • Journal Title: General Thoracic and Cardiovascular Surgery Volume: 67 Issue: 7 Pages: 615-623
  • DOI: 10.1007/s11748-019-01062-1
  • Peer Reviewed
• [Journal Article] Ligating the pulmonary vein at the pericardial reflection is useful for preventing thrombus formation in the pulmonary vein stump after left upper lobectomy. (2019)
  • Author(s): Nakano T, Kaneda H, Kawaura T, Kitawaki T, Murakawa T.
  • Journal Title: General Thoracic and Cardiovascular Surgery Volume: 67 Issue: 5 Pages: 450-456
  • DOI: 10.1007/s11748-018-1032-9
  • Peer Reviewed
• [Journal Article] Role of Toll-like Receptor 4 Expressed by Fibroblasts in Allograft Fibrosis in Mouse Orthotopic Tracheal Transplantation. (2018)
  • Author(s): Kawashima M, Sato M, Murakawa T, Anraku M, Konoeda C, Hosoi A, Kakimi K, Nakajima J.
  • Journal Title: Transplant Proc. Volume: 50 Issue: 10 Pages: 3863-3872
  • DOI: 10.1016/j.transproceed.2018.06.023
  • Peer Reviewed
• [Journal Article] Comparative study of programmed cell death ligand-1 immunohistochemistry assays using 22C3 and 28-8 antibodies for non-small cell lung cancer: Analysis of 420 surgical specimens from Japanese patients. (2018)
  • Author(s): Saito T, Tsuta K, Ishida M, Ryota H, Takeyasu Y, Fukumoto KJ, Matsui H, Taniguchi Y, Yanagimoto H, Kurata T, Murakawa T.
  • Journal Title: Lung Cancer. Volume: 125 Pages: 230-237
  • DOI: 10.1016/j.lungcan.2018.10.005
  • Peer Reviewed
• [Journal Article] Combined small cell carcinoma with giant cell carcinoma component of the lung: A case successfully diagnosed by computed tomography-guided fine-needle aspiration cytology. (2018)
  • Author(s): Ebisu Y, Ishida M, Saito T, Murakawa T, Uemura Y, Tsuta K.
  • Journal Title: Oncol Lett. Volume: 15(2) Pages: 1907-1911
  • DOI: 10.3892/ol.2017.7448
  • Peer Reviewed / Open Access
• [Journal Article] Thymic enteric type adenocarcinoma: A case report with cytological features. (2018)
  • Author(s): Tamai M, Ishida M, Ebisu Y, Okamoto H, Miyasaka C, Ohe C, Uemura Y, Saito T, Murakawa T, Tsuta K.
  • Journal Title: Diagn Cytopathol. Volume: 46(1) Issue: 1 Pages: 92-97
  • DOI: 10.1002/dc.23806
  • Peer Reviewed
• [Journal Article] Combined small cell lung carcinoma and giant cell carcinoma: a case report. (2017)
  • Author(s): Saito T, Tsuta K, Fukumoto KJ, Matsui H, Konobu T, Torii Y, Yokoi T, Kurata T, Kurokawa H, Uemura Y, Saito Y, Murakawa T.
  • Journal Title: Surg Case Rep. Volume: 3(1) Issue: 1 Pages: 52-52
  • DOI: 10.1186/s40792-017-0328-9
  • Peer Reviewed / Open Access
• [Journal Article] Thoracoscopic surgery versus open surgery for lung metastases of colorectal cancer: a multi-institutional retrospective analysis using propensity score adjustment. (2017)
  • Author(s): Murakawa T, Sato H, Okumura S, Nakajima J, Horio H, et al; Metastatic Lung Tumor Study Group of Japan.
  • Journal Title: Eur J Cardiothorac Surg. Volume: 51(6) Issue: 6 Pages: 1157-1163
  • DOI: 10.1093/ejcts/ezx020
  • Peer Reviewed
• [Journal Article] A deep azygoesophageal recess may increase the risk of secondary spontaneous pneumothorax. (2017)
  • Author(s): Takahashi T, Kawashima M, Kuwano H, Nagayama K, Nitadori J, Anraku M, Sato M, Murakawa T, Nakajima J.
  • Journal Title: Surg Today. Volume: 47(9) Issue: 9 Pages: 1147-1152
  • DOI: 10.1007/s00595-017-1482-1
  • Peer Reviewed
• [Presentation] 新たな胸腺扁平上皮癌特異的マーカーPRAMEの有用性 (2020)
  • Author(s): 谷口洋平、石田光明、齊藤朋人、良田大典、内海貴博、丸夏未、松井浩史、日野春秋、蔦幸治、村川知弘
  • Organizer: 第39回日本胸腺研究会
• [Presentation] Cancer/testis antigen PRAME is a useful diagnostic marker and potential target for antigen-specific immunotherapy for thymic squamous cell carcinoma (2019)
  • Author(s): Taniguchi Y, Ishida M, Saito T, Ryota H, Utsumi T, Maru N, Matsui H, Hino H, Tsuta K, Murakawa T
  • Organizer: 10th International Thymic Malignancy Interest Group Annual Meeting
  • Int'l Joint Research
• [Presentation] 新たな胸腺扁平上皮癌特異的マーカーPRAMEの有用性と臨床応用に向けて (2019)
  • Author(s): .谷口洋平、石田光明、齊藤朋人、内海貴博、丸夏未、松井浩史、日野春秋、蔦幸治、村川知弘
  • Organizer: 谷口洋平、石田光明、齊藤朋人、内海貴博、丸夏未、松井浩史、日野春秋、蔦幸治、村川知弘
• [Presentation] Biologic profiling of pre-metastatic niche in completely resected pathological stage i non-small cell lung cancer. (2018)
  • Author(s): Saito T, Ryota H, Ishida M, Fukumoto K, Matsui H, Taniguchi Y, Yanagimoto H, Tsuta K, Murakawa T
  • Organizer: 19th World Conference on Lung Cancer
  • Int'l Joint Research
• [Presentation] Biologic profiling of brain metastasis from nonsmall cell lung cancer. (2018)
  • Author(s): Saito T, Iwata R, Maruyama M, Nakano Y, Ofune K, Matsuda S, Kaibori M, Murakawa T, Hayashi M
  • Organizer: 19th World Conference on Lung Cancer
  • Int'l Joint Research
• [Presentation] Toll-like receptor 4 signaling affects myofibroblasts expression in mice tracheal allograft (2018)
  • Author(s): Kawashima M, Sato M, Murakawa T, Anraku M, Konoeda C, Hosoi A, Kakimi K, Nakajima J
  • Organizer: 38th ISHLT annual meeting and scientific sessions
• [Presentation] Comparison Study of PD-L1 Immunohistochemistry Assays with 22C3 and 28-8: Analysis on Surgical Specimens of NSCLC. (2017)
  • Author(s): Saito T, Tsuta K, Ishida M, Ryota H, Takeyasu Y, Fukumoto J, Matsui H, Taniguchi Y, Yanagimoto H, Yokoi T, Kurata T, Murakawa T
  • Organizer: 18th World Conference on Lung Cancer
• [Presentation] A case of thymic cyst with papillary proliferation of ciliated epithelium. (2017)
  • Author(s): Matsui H, Taniguchi Y, Saito T, Tsuta K, Murakawa T
  • Organizer: 8th International Thymic Malignancy Interest Group Annual Meeting
• [Presentation] Preoperative biopsy does not affect outcomes of resectable non-small cell lung cancer: a propensity score-matched analysis (2017)
  • Author(s): Taniguchi Y, Kozuka T, Fukumoto K, Matsui H, Saito T, Murakawa T
  • Organizer: 31th European Association for Cardio-thoracic Surgery Annual Meeting
• [Presentation] Clinical and pathological characteristics of spontaneous pneumothorax in women: a 25-year single-institutional experience. (2017)
  • Author(s): Saito T, Saito Y, Fukumoto KJ, Matsui H, Nakano T, Taniguchi Y, Kaneda H, Konobu T, Sakaida Nm Okamura A, Uemura Y, Tsuta K, Murakawa T
  • Organizer: CHEST Annual Meeting 2017
• [Remarks] 関西医科大学呼吸器外科学講座HP
  • URL: http://www3.kmu.ac.jp/thorsurg/index.html
• [Remarks] 関西医科大学呼吸器外科学講座
  • URL: http://www3.kmu.ac.jp/thorsurg/index.html
• [Remarks] 関西医科大学呼吸器外科講座
  • URL: http://www3.kmu.ac.jp/thorsurg/index.html