研究の概要

消化管に発生する間葉系腫瘍であるGastrointestinal stromal tumor (GIST)の発生機序や起源細胞についての研究を行い、GISTの治療に関わる研究も行ってきた。最近では、GISTのさらなる病態解析や治療に対する耐性機構の解明などの研究を分子病理学的に進めている。また、動脈硬化や大動脈瘤などの循環器疾患に関する病理学的研究や肺癌、軟部腫瘍、血液疾患の研究なども行っている。様々な臨床症例についての病理学的検索・考察に関する症例報告も行っている。


主な内容

1．GISTの病態・治療に関する研究：多発性GIST家系のモデルとなるノックインマウス（germlineにc-kit遺伝子の機能獲得性突然変異を導入）を作製し、カハールの介在細胞の過形成からGIST発生に至るメカニズムを検討している。また、GISTにみられる様々なタイプのc-kitおよびPDGFRA遺伝子変異の特性や分子標的薬イマチニブに耐性を示すGISTの耐性メカニズムについての研究も進めている。(2003年までのGISTに関する研究経過の詳細を見る場合はここをクリックして下さい)

2．循環器疾患に関する病理学的研究：冠動脈および頸動脈にみられる粥状硬化の性状と心筋梗塞・脳梗塞との関連につき臨床病理学的なアプローチでの研究を行っている。また、これまでの血管平滑筋細胞の多様性に関する研究を基礎に、様々なフェノタイプを示す平滑筋細胞と大動脈瘤の形成との関係や大動脈瘤に見られる平滑筋細胞のアポトーシスの機序、各種心血管疾患における小胞体ストレス関連分子の役割についての研究も進めている。


＜教室主導で行われた最近の論文発表（2015年～）＞

●英文

Ikeo K, Matsuda I, Hirota S. EBV-positive bile duct carcinoma associated with ulcerative colitis. Intern Med. 2023 In press

Sano D, Kihara T, Yuan J, Kimura N, Ohkouchi M, Hashikura Y, Ohkubo S, Hirota S. Characterization of cell line with dedifferentiated GIST‐like features established from cecal GIST of familial GIST model mice. Pathol Int. in press

Matsuda I, Hirota S. Dutcher bodies as a diagnostic key to POEMS syndrome. eJHaem. In press

Kihara T, Kuwahara R, Kusunoki K, Minagawa T, Horio Y, Uchino M, Ikeuchi H, Hirota S. Rectal carcinoma with dual differentiation toward enteroblastic and neuroendocrine features arising in a patient with ulcerative colitis: a case report. World J Surg Oncol. 20:371, 2022.

Yuan J, Kihara T, Kimura N, Yamasaki T, Yoshida M, Isozaki K, Ito A, Hirota S. CADM1 promotes adhesion to vascular endothelial cells and transendothelial migration in cultured GIST cells. Oncol Lett. 23:86, 2022.

Yoshiyasu K, Kono H, Hojo Y, Ishida Y, Tamura A, Nakai K, Oshima T, Miwa H, Shinohara H, Hirota S. A minute primary gastric synovial sarcoma with ulcer: a case report. Diagn Pathol. 16:115, 2021. (case report)

Nambu N, Yamasaki T, Nakagomi N, Kumamoto T, Nakamura T, Tamura A, Tomita T, Miwa H, Shinohara H, Hirota S. A case of ectopic pancreas of the stomach accompanied by intraductal papillary mucinous neoplasm with GNAS mutation. World J Surg Oncol. 19:309, 2021. (case report)

Kihara T, Yuan J, Watabe T, Kitajima K, Kimura N, Ohkouchi M, Hashikura Y, Ohkubo S, Takahashi T, Hirota S. Pimitespib is effective on cecal GIST in a mouse model of familial GISTs with KIT-Asp820Tyr mutation through KIT signaling inhibition. Exp Mol Pathol. 23:104692, 2021.

Yuan J, Kihara T, Kimura N, Hashikura Y, Ohkouchi M, Isozaki K, Takahashi T, Nishida T, Ito A, Hirota S. Differential expression of CADM1 in gastrointestinal stromal tumors of different sites and with different gene abnormalities. Pathol Oncol Res. 27:602008, 2021.

Shintaku Y, Asano Y, Watanabe T, Kihara T, Ishikawa E, Jiayin Y, Kimura N, Kinoshita K, Hirota S. A case of planar-type GIST of the sigmoid colon showing diverticular structure with perforation. World J Surg Oncol. 18:125, 2020. (case report)

Nakagomi N, Sakamoto D, Hirose T, Takagi T, Murase M, Nakagomi T, Yoshimura S, Hirota S. Epithelioid glioblastoma with microglia features: potential for novel therapy. Brain Pathol. 30:1119-1133, 2020. 

Torii Y, Sano D, Ikeuchi H, Hida N, Hirota S. Use of segmental colorectal lavage cytology during surveillance colonoscopy for detecting dysplastic and cancer cells in patients with ulcerative colitis. Int J Clin Exp Pathol. 13:2035-2040, 2020.

Nakanishi M, Watari J, Tomita T, Nakanishi Y, Tsukamoto Y, Matsuo S, Uchihashi T, Miyazaki J, Tanaka H, Kojima S, Kuroda N, Matsuda I, Miwa H, Shinohara H, Hirota S. Gastric CLTC-ALK fusion-positive inflammatory myofibroblastic tumor showing an endoscopic superficial depressed-type appearance. Human Pathology: Case Reports. 15:73-78, 2019. (case report)

Matsuda I, Nakamura J, Ohkouchi M, Torii Y, Futani H, Tsukamoto Y, Hirota S.Expression of p16 in nodular fasciitis: an implication for self-limited and inflammatory nature of the lesion. Int J Clin Exp Pathol. 12:1029-1034, 2019. 

Kawakami R, Imanaka T, Ishihara M, Kihara T, Fujii K, Hirota S, Hao H. Protruding in-stent mass after bioresorbable polymer sirolimus-eluting stent: ex vivo intravascular images and histopathology. Circ J. 82:932-933, 2018. (case report)

Tsukamoto Y, Takahata H, Teramoto N, Nishimura R, Hato S, Nozaki I, Matsuo S, Hirota S. Primary gastric low-grade fibromyxoid sarcoma with FUS-CREB3L1 fusion - a hitherto undescribed origin of Evans tumor. Human Pathology: Case Reports. 11:51-55, 2018. (case report)

Matsuda I, Hirota S. Methotrexate-associated lymphoproliferative disorder masquerading as multiple cerebral metastases. Br J Haematol. (Images in Haematology) 180:628, 2018. (case report)

Watanabe T, Hida AI, Inoue N, Imamura M, Fujimoto Y, Akazawa K, Hirota S, Miyoshi Y. Abundant tumor infiltrating lymphocytes after primary systemic chemotherapy predicts poor prognosis in estrogen receptor-positive/HER2-negative breast cancers. Breast Cancer Res Treat. 168:135-145, 2018.

Kawakami R, Hao H, Imanaka T, Shibuya M, Ueda Y, Tsujimoto M, Ishibashi-Ueda H, Hirota S. Initial pathological responses of second-generation everolimus-eluting stents implantation in Japanese coronary arteries: Comparison with first-generation sirolimus-eluting stents. J Cardiol. 71:452-457, 2018.

Tsuchida Y, Tsukamoto Y, Futani H, Kumanishi S, Watanabe T, Kajimoto N, Matsuo S, Yoshiya S, Hirota S. A rare case of low-grade fibromyxoid sarcoma with ossification which was radiologically detected as apparent calcification and histopathologically proven. Human Pathology: Case Reports. 12:24-28, 2018. (case report)

Matsuda I, Hirota S. Pautrier-like microabscesses in the tonsil. Blood. 131:2177, 2018. (case report) 

Fujino A, Hao H, Shimodai S, Kawakami R, Matsuo K, Yasumura Y, Higuchi Y, Tsujimoto M, Ueda Y, Hirota S. Atherosclerotic plaque component as a risk for distal embolization during percutaneous coronary intervention; pathological assessment of tissue obtained by distal protection device. Circ J. 82:2292-2298, 2018.

Tsukamoto Y, Futani H, Kihara T, Watanabe T, Kumanishi S, Matsuo S, Hirota S, Ueda T, Yamamoto H, Yoshiya S. An extremely rare case of primary malignancy in giant cell tumor of bone, arising in the right femur and harboring H3F3A mutation. Pathol Res Pract. 214:1504-1509, 2018. (case report)

Tsukamoto Y, Futani H, Watanabe T, Kemmoku K, Iwayama T, Matsuo S, Hirota S, Yoshiya S. Two cases of WWTR1-CAMTA1 fusion-positive epithelioid hemangioendotheliomas with extremely different outcomes. Human Pathology: Case Reports. 14:25-32, 2018. (case report)

Watanabe T, Ukon S, Kihara T, Ide Y-H, Matsuo S, Hayashi, Y, Kasama S, Yoshikawa H, Okano Y, Uchida C, Yamamoto M, Hao H, Kimura A, Hirota S, Tsukamoto Y. An autopsy case of amyloid β-related angiitis with cognitive impairment, multiple infarcts and subcortical hemorrhage. Human Pathology: Case Reports. 14:47-51, 2018. (case report)

Kono H, Tsukamoto Y, Matsuo S, Hashidate H, Shibuya H, Kobayashi T, Takii Y, Hirota S. The first case of rectal myxoid liposarcoma identified by FUS-DDIT3 fusion, presenting as a submucosal tumor with erosion. Human Pathology: Case Reports.14:92-95, 2018. (case report)

Nakamura K, Nonaka S, Nakajima T, Yachida T, Abe S, Sakamoto T, Suzuki H, Yoshinaga S, Oda I, Matsuda T, Sekine S, Kanemitsu Y, Katai H, Saito Y, Hirota S. Clinical outcomes of gastric polyps and neoplasms in patients with familial adenomatous polyposis. Endosc Int Open. 5:E137-E145, 2017.

Kawakami R, Hao H, Tsuchida YA, Fujino A, Imanaka T, Saita T, Fujii K, Ishihara M, Hirota S. Neoatherosclerosis after paclitaxel-eluting stent implantation: ex vivo intravascular image and histopathology. Pathol Int. 67:53-55, 2017. (case report)

Tsukamoto Y, Futani H, Yoshiya S, Watanabe T, Kihara T, Matsuo S, Hirota S. Primary undifferentiated small round cell sarcoma of the deep abdominal wall with a novel variant of t(10;19) CIC-DUX4 gene fusion. Pathol Res Pract. 213:1315-1321, 2017. (case report)

Tsukamoto Y, Kurajyoh M, Koyama H, Kakibuchi M, Yamamoto S, Miyamoto Y, Hao H, Hirota S. A case of Carney complex misdiagnosed as neurofibromatosis type 1 - diagnostic difficulty in a rare disease - Human Patholology: Case Reports. 10:56-59, 2017. (case report)

Nambu N, Tsukamoto Y, Tsuji H, Watanabe T, Shigehara R, Kakibuchi M, Morii E, Hirota S. Invasive ductal carcinoma ex pleomorphic adenoma of the lacrimal gland - a long term follow-up case - Human Pathology: Case Reports. 10:81-84, 2017. (case report)

Kihara T, Tsukamoto Y, Yabuuchi T, Teramoto Y, Yugami H, Yamada K, Nagatsuka K, Matsuo S, Hirota S. A case of meningeal myxoid solitary fibrous tumor/hemangiopericytoma with unique NAB2-STAT6 fusion gene and symptomatic intratumoral hemorrhage. Human Pathology: Case Reports. 10:85-88, 2017. (case report)

Tsukamoto Y, Futani H, Kumanishi S, Watanabe T, Kihara T, Hirota S. A rare case of Ewing sarcoma with elevated plasma pro-gastrin-releasing peptide (proGRP) level. Human Pathology: Case Reports. 6:13-18, 2016. (case report)

Tsukamoto Y, Imakita M, Nishitani A, Ito T, Izukura M, Hirota S. Pancreatic desmoid-type fibromatosis with beta-catenin gene mutation - report of a case and review of the literature. Pathol Res Pract. 212:484-489, 2016. (case report)

Fujino A, Hao H, Kawakami R, Tsuchida YA, Fujii K, Hirota S. Ex vivo optical frequency domain imaging and histopathology of malapposed drug eluting stent in coronary artery. Pathol Int. 66:354-355, 2016. (case report)

Fujino A, Hao H, Kawakami R, Tsuchida YA, Imanaka T, Saita T, Fujii K, Ishihara M, Hirota S. Ulcerated plaque of coronary artery: insights from ex vivo images of optical frequency domain imaging and histopathology. Pathol Int. 66:643-644, 2016. (case report) 

Matsuda I, Yamamoto A, Shimizu Y, Matsuo S, Ohsawa M, Hirota S. CD31 is a surrogate marker for blastic plasmacytoid dendritic cell neoplasm: a case of a hematologic skin tumor immunohistochemically false negative for CD45. Int J Clin Exp Pathol. 9:7622-7628, 2016. (case report)

Tsukamoto Y, Hao H, Kajimoto N, Katayama A, Suzuki C, Terada T, Nakano T, Hanaoka K, Hirota S. Sarcomatoid pleural mesothelioma withosteosarcomatous, chondrosarcomatous andrhabdomyoblastic elements: an extremely rare autopsy case. Pathol Int. 65:51-53, 2015. (case report) 

Matsuda I, Sugihara N, Yunokizaki H, Abe T, Hirota S. A case of immunohistochemical false positive staining caused by incompatibility between a CD4 antibody and an autostainer. Int J Clin Exp Pathol. 8:1019-1024, 2015. (case report) 

Fujino A, Hao H, Kajimoto N, Kawakami R, Imanaka T, Fujii K, Abe T, Ishihara M, Hirota S. Restenosis after drug-eluting stent implantation in a patient with polycythemia vera: optical coherence tomography and pathological findings. JACC Cardiovasc Interv. 8:e111-112, 2015. (case report)

Ide Y, Tsukamoto Y, Ito T, Watanabe T, Nakagawa N, Haneda T, Nagai M, Yamanishi K, Hirota S. Penile pseudomyogenic hemangioendothelioma/epithelioid sarcoma-like hemangioendothelioma with a novel pattern of SERPINE1-FOSB fusion detected by RT-PCR - report of a case. Pathol Res Pract. 211:415-420, 2015. (case report)

Kawakami R, Hao H, Kimura N, Komatsu S, Kodama K, Hirota S. Pathological evaluation of massive left atrial calcification 35 years after mitral-aortic valve replacement. J Cardiol Cases. 11:44-47, 2015. (case report) 

Fujino A, Hao H, Kawakami R, Fujii K, Imanaka T, Ishihara M, Tsuchida Y, Hirota S. Is optical frequency domain imaging a promising modality for diagnosis of erosion? Pathol Int. 65:617-618, 2015. (case report)

Kajimoto N, Hao H, Kawakami R, Takagi Y, Fujino A, Sugahara M, Masuyama T, Hirota S. Cardiac sarcoidosis predominantly involved in right ventricle: an autopsy case. Pathol Int. 65:619-21, 2015. (case report)

Matsuda I, Tsuchida Y, Toyoshima F, Tozawa K, Ikehara H, Ohda Y, Hori K, Ohtsuka Y, Watari J, Miwa H, Hirota S. Occurrence of colon tumors in a 16-year-old Japanese boy after hematopoietic stem cell transplantation for Diamond Blackfan anemia at age of 4: a case report. Int J Clin Exp Pathol. 8:5938-5943, 2015. (case report)

Kawakami R, Hao H, Takagi Y, Fujino A, Tsuchida YA, Imanaka T, Fujii K, Hirota S. Drug-eluting stent implantation on calcified nodule: ex vivo intravascular images and histopathology. JACC Cardiovasc Interv. 8:e127-128, 2015. (case report)

Tsukamoto Y, Otsuki T, Hao H, Kuribayashi K, Nakano T, Kida A, Nakanishi T, Funatsu E, Noguchi C, Yoshihara S, Kaku Koji, Hirota S. Epithelioid pleural mesothelioma concurrently associated with miliary pulmonary metastases and minimal change nephrotic syndrome - a hitherto undescribed case. Pathol Res Pract. 211:1014-1019, 2015. (case report) 

Kajimoto N, Tsukamoto Y, Hao H, Watanabe T, Tsubamoto H, Kuribayashi K, Kamiya H, Shibata E, Nakano T, Hirota S. Uterine metastasis of lung adenocarcinoma revealed by the same epidermal growth factor receptor mutation in both lung and endometrial biopsies. Cancer Treat Comm. 4:134-137, 2015. (case report)

Matsuda I, Kan K, Doi S, Motoki Y, Onodera M, Hirota S. A case of gastric cancer with heterogeneous components of EB virus (+)/TP53 (+) and EB virus (-)/TP53 (-). Int J Clin Exp Pathol. 8:11766-11771, 2015. (case report)

Kajimoto N, Nakai N, Ohkouchi M, Hashikura Y, Liu-Kimura N-N, Isozaki K, Hirota S. Characterization of various types of mast cells derived from model mice of familial gastrointestinal stromal tumors with KIT-Asp818Tyr mutation. Int J Clin Exp Pathol. 8:11970-11982, 2015.

 

●和文

糸山雅子，中村純子，佐藤元，石田圭子，榎本利香，鳥居良貴，石川恵理，井出良浩，渡邊隆弘，廣田誠一．オンサイト迅速細胞診における湿固定簡易ギムザ染色の有用性．日本臨床細胞学会雑誌60-3: 141-149, 2021.

石田誠実，中西昂弘，鳥居良貴，廣田誠一．マイクロチューブを利用した細胞浮遊状態での免疫細胞化学染色法の検討．日本臨床細胞学会雑誌59-5: 248-250, 2020.

石川恵理, 木原多佳子, 毛利武士, 貴田紘太, 塚本吉胤, 廣田誠一. β-catenin (CTNNB1) 遺伝子変異検索が確定診断に有用であった Glomangiopericytoma の一例. 診断病理. 37-2, 278-282,2020.（症例報告）

中西昂弘，佐藤元，糸山雅子，中村純子，鳥居良貴，渡邊隆弘，中込奈美，井出良浩，松田育雄，廣田誠一．LBC法を用いた体腔液検体の細胞学的検討．日本臨床細胞学会雑誌58-6: 231-240, 2019.

鳥居洋祐, 大西崇文, 長友忠相, 佐藤元, 中村純子, 鳥居良貴, 森井英一, 廣田誠一. 施行者間差の少ないグロコット染色法の工夫　- クロム酸アンモニウム銀法における菌体ごとの至適時間の検討 -. 医学検査 67(2):221-227, 2018.

石田誠実，中西昂弘，西上圭子，佐藤元，中村純子，鳥居良貴，塚本吉胤，廣田誠一．淡明細胞軟骨肉腫の一例．日本臨床細胞学会雑誌55-3: 160-164, 2016. （症例報告）

＜最近の教室内の学位取得状況＞

佐野太亮2022年
（学位論文名）
Sano D, Kihara T, Yuan J, Kimura N, Ohkouchi M, Hashikura Y, Ohkubo S, Hirota S. Characterization of cell line with dedifferentiated GIST‐like features established from cecal GIST of familial GIST model mice. Pathol Int. in press

木原多佳子2021年
（学位論文名）
Kihara T, Yuan J, Watabe T, Kitajima K, Kimura N, Ohkouchi M, Hashikura Y, Ohkubo S, Takahashi T, Hirota S. Pimitespib is effective on cecal GIST in a mouse model of familial GISTs with KIT-Asp820Tyr mutation through KIT signaling inhibition. Exp Mol Pathol. 23:104692, 2021.

袁嘉茵2021年
（学位論文名）
Yuan J, Kihara T, Kimura N, Hashikura Y, Ohkouchi M, Isozaki K, Takahashi T, Nishida T, Ito A, Hirota S. Differential expression of CADM1 in gastrointestinal stromal tumors of different sites and with different gene abnormalities. Pathol Oncol Res. 27:602008, 2021.

川上りか2018年
（学位論文名）
Kawakami R, Hao H, Imanaka T, Shibuya M, Ueda Y, Tsujimoto M, Ishibashi-Ueda H, Hirota S. Initial pathological responses of second-generation everolimus-eluting stents implantation in Japanese coronary arteries: Comparison with first-generation sirolimus-eluting stents. J Cardiol. 71:452-457, 2018.

藤野明子2018年
（学位論文名）
Fujino A, Hao H, Shimodai S, Kawakami R, Matsuo K, Yasumura Y, Higuchi Y, Tsujimoto M, Ueda Y, Hirota S. Atherosclerotic plaque component as a risk for distal embolization during percutaneous coronary intervention; pathological assessment of tissue obtained by distal protection device. Circ J. 82:2292-2298, 2018.

渡邊隆弘2018年
（学位論文名）
Watanabe T, Hida AI, Inoue N, Imamura M, Fujimoto Y, Akazawa K, Hirota S, Miyoshi Y. Abundant tumor infiltrating lymphocytes after primary systemic chemotherapy predicts poor prognosis in estrogen receptor-positive/HER2-negative breast cancers. Breast Cancer Res Treat. 168:135-145, 2018.

中村佳子2017年
（学位論文名）
Nakamura K, Nonaka S, Nakajima T, Yachida T, Abe S, Sakamoto T, Suzuki H, Yoshinaga S, Oda I, Matsuda T, Sekine S, Kanemitsu Y, Katai H, Saito Y, Hirota S. Clinical outcomes of gastric polyps and neoplasms in patients with familial adenomatous polyposis. Endosc Int Open. 5:E137-E145, 2017.

梶本仙子2016年
（学位論文名）
Kajimoto N, Nakai N, Ohkouchi M, Hashikura Y, Liu-Kimura N-N, Isozaki K, Hirota S. Characterization of various types of mast cells derived from model mice of familial gastrointestinal stromal tumors with KIT-Asp818Tyr mutation. Int J Clin Exp Pathol. 8:11970-11982, 2015.

劉寧寧2013年
（学位論文名）
Liu N-N, Ohkouchi M, Hashikura Y, Kajimoto N, Matsuda I, Isozaki K, Toh Y, Takahashi T, Nishida T, Hirota S. Extracellular domain c-kit gene mutation of duplication of Ser501Ala502 found in gastrointestinal stromal tumors is more imatinib- and nilotinib-sensitive than that of duplication of Ala502Tyr503. Lab Invest. 93:502-507, 2013.

中井真由美2012年
（学位論文名）
Nakai M, Hashikura Y, Ohkouchi M, Yamamura M, Akiyama T, Shiba K, Kajimoto N, Tsukamoto Y, Hao H, Isozaki K, Hirai T, Hirota S. Characterization of novel germline c-kit gene mutation, KIT-Tyr553Cys, observed in a family with multiple gastrointestinal stromal tumors. Lab Invest. 92:451-457, 2012.

造住誠孝2012年
（学位論文名）
Zozumi M, Nakai M, Ito T, Matsuda I, Hao H, Tsukamoto Y, Hirota S. New double embedding technique for specimens of endoscopic submucosal dissection using agarose: comparison with other media. J Clin Pathol. 63:904-909, 2010.

研究内容