基本情報
- 所属
- 自治医科大学 医学部 病理学講座・附属病院病理診断部 教授 (部長)(兼任)病理診断科 診療科長
- 学位
- 医学博士(東京大学)
- J-GLOBAL ID
- 201401077459790889
- researchmap会員ID
- B000237516
- 外部リンク
・平成2年 宮崎医科大学卒業
・平成2年 NTT関東逓信病院
臨床研修医(消化器内科・外科・画像診断・病理)・専修医(病理診断科)
・平成7年 国立がんセンター研究所支所 臨床腫瘍病理部 リサーチ・レジデント
・平成9年 国立がんセンター中央病院 臨床検査部 医員
・平成13年 ジョンズ・ホプキンス大学医学部 病理部 研究員
・平成16年 東京医科大学 病理診断学講座 講師
・平成17年 東京大学大学院医学系研究科 病理学講座 講師
・平成18年 東京大学大学院医学系研究科 病理学講座 准教授
東京大学病院病理部 副部長
・平成21年 自治医科大学医学部病理学講座 教授
自治医科大学附属病院 病理診断部 部長
(平成26年~自治医科大学附属病院 病理診断科 科長)
・平成2年 NTT関東逓信病院
臨床研修医(消化器内科・外科・画像診断・病理)・専修医(病理診断科)
・平成7年 国立がんセンター研究所支所 臨床腫瘍病理部 リサーチ・レジデント
・平成9年 国立がんセンター中央病院 臨床検査部 医員
・平成13年 ジョンズ・ホプキンス大学医学部 病理部 研究員
・平成16年 東京医科大学 病理診断学講座 講師
・平成17年 東京大学大学院医学系研究科 病理学講座 講師
・平成18年 東京大学大学院医学系研究科 病理学講座 准教授
東京大学病院病理部 副部長
・平成21年 自治医科大学医学部病理学講座 教授
自治医科大学附属病院 病理診断部 部長
(平成26年~自治医科大学附属病院 病理診断科 科長)
研究分野
1経歴
2-
2009年9月 - 現在
-
2014年
論文
422-
Cancer medicine 13(13) e7431 2024年7月BACKGROUND: Cancer utilizes immunosuppressive mechanisms to create a tumor microenvironment favorable for its progression. The purpose of this study is to histologically characterize the immunological properties of the tumor microenvironment of oral squamous cell carcinoma (OSCC) and identify key molecules involved in the immunological microenvironment and patient prognosis. METHODS: First, overlapping differentially expressed genes (DEGs) were screened from OSCC transcriptome data in public databases. Correlation analysis of DEGs with known immune-related genes identified genes involved in the immune microenvironment of OSCC. Next, stromal patterns of tumor were classified and immunohistochemical staining was performed for immune cell markers (CD3, CD4, Foxp3, CD8, CD20, CD68, and CD163), programmed death-ligand 1 (PD-L1), and guanylate binding protein 5 (GBP5) in resected specimens obtained from 110 patients with OSCC who underwent resection. Correlations between each factor and their prognostic impact were analyzed. RESULTS: Among the novel OSCC-specific immune-related genes screened (including ADAMDEC1, CXCL9, CXCL13, DPT, GBP5, IDO1, and PLA2G7), GBP5 was selected as the target gene. Histopathologic analysis showed that multiple T-cell subsets and CD20-positive cells were less common in the advanced stages, whereas CD163-positive cells were more common in advanced stages. The immature type in the stromal pattern category was associated with less immune cell infiltration, lower expression of PD-L1 in immune cells, lower expression of GBP5 in the stroma, and shorter overall survival and recurrence-free survival. Expression of GBP5 in the tumor and stroma correlated with immune cell infiltration of tumors and PD-L1 expression in tumor and immune cells. Patients with low tumor GBP5 expression and high stromal expression had significantly longer overall survival and recurrence-free survival. CONCLUSIONS: The stromal pattern category may reflect both invasive and immunomodulatory potentials of cancer-associated fibroblasts in OSCC. GBP5 has been suggested as a potential biomarker to predict the prognosis and therapeutic efficacy of immune checkpoint inhibitors.
-
Science progress 107(3) 368504241274022-368504241274022 2024年Maxillary angiosarcoma, an aggressive tumor derived from vascular endothelial cells, is very rare. Recently, antivascular endothelial growth factor (VEGF) therapies have attracted considerable attention. We describe the clinical course of a patient with maxillary angiosarcoma and discuss the expression of VEGF signaling molecules assessed via immunohistological analysis. An 81-year-old man presented with an aggressive tumor in the left maxillary sinus. Biopsy revealed atypical nuclear cell proliferation, and the tumor was suspected to be a sarcoma. The maxillary malignancy was treated using a multidisciplinary approach with a combination of surgery, radiotherapy, and regional chemotherapy. Examination of the specimen obtained in the first surgery revealed maxillary angiosarcoma, found to be positive for CD31, while negative for CD34, D2-40, and factor Ⅷ. Although no pathological residual tumor was observed after the planned wide surgery, cervical lymph node and distant metastases occurred. The patient died 24 months after the first surgery. Staining revealed VEGF receptor (VEGFR) 1, VEGFR2, phosphorylated Ak strain transforming, mitogen-activated protein kinase, and signal transducer and activator of transcription 3 positivity. Although our findings do not indicate that anti-VEGF therapy is beneficial for treating maxillary angiosarcomas, we found that VEGFR signaling pathways were activated in maxillary angiosarcomas similar to angiosarcomas originating at other sites. Herein, we report a case of maxillary angiosarcoma, focused on VEGFR and signaling pathway activation. To our knowledge, this is the first report to describe VEGFR system immunostaining findings in maxillary angiosarcoma.
-
Frontiers in medicine 11 1247625-1247625 2024年INTRODUCTION: The Hippo pathway consists of mammalian sterile 20-like kinase 1/2 (MST1/2), large tumor suppressor 1/2 (LATS1/2), and yes-associated protein (YAP)1. Herein, we present the first report on the significance of major Hippo pathway protein expression in oral squamous cell carcinoma (OSCC). METHODS: The analyses included oral epithelial dysplasia (OED, n = 7), carcinoma in situ (CIS, n = 14), and oral squamous cell carcinoma (OSCC, n = 109). RESULTS: Cytoplasmic expression of MST1, LATS1, and LATS2 was low in OED, CIS, and OSCC. The cytoplasmic expression of MST2 was high in OED (5/7 cases), CIS (9/14 cases), and poorly differentiated OSCC (8/8 cases) but was low/lost in a proportion of differentiated OSCC (60/101 cases). The expression of YAP1 was associated with differentiation; low YAP expression was significantly more frequent in well-differentiated OSCC (35/71 cases), compared to moderately and poorly differentiated OSCC (11/38 cases). An infiltrative invasion pattern was associated with a high expression of MST2 and high expression of YAP1. The high expression of YAP1 was associated with features of epithelial-to-mesenchymal transition (EMT), such as the loss of E-cadherin and high expression of vimentin, laminin 5, and Slug. High expression of protein arginine methyltransferase (PRMT) 1 or 5, which positively regulates YAP activity, was associated with the high expression of YAP1 (p < 0.0001). CONCLUSION: Among the major Hippo pathway proteins, MST2 displayed a distinctive expression pattern in a significant proportion of differentiated OSCC, suggesting a possible differential role for MST2 depending on the course of OSCC progression. A high YAP1 expression may indicate aggressive OSCC with EMT via PRMTs at the invasive front.
-
Virchows Archiv : an international journal of pathology 2023年9月28日The present study immunohistochemically investigated trimethylation of lysine 27 of histone 3 (H3K27me3) expression in 769 endometrial carcinomas and 196 uterine mesenchymal tumors. One dedifferentiated endometrial carcinoma (DEC) and one carcinosarcoma showed H3K27me3 deficiency that was limited to undifferentiated and sarcomatous components, respectively. Switch/sucrose nonfermenting (SWI/SNF) complex subunits (SMARCA4, SMARCB1, and ARID1A/1B) and mismatch repair proteins were proficient in both tumors. The dimethylation of H3K27 (H3K27me2) was deficient in the undifferentiated component, whereas the sarcomatous component had scattered H3K27me2-positive cells. CXorf67, which inhibits PRC2 function, was diffusely expressed in the sarcomatous component. CXorf67 was negative in the undifferentiated component, which was submitted to a genetic analysis and showed no alterations in PRC2 core subunits or H3K27. The present results suggest H3K27 methylation dysregulation as a cause of SWI/SNF-proficient DEC and carcinosarcoma and imply differences in their level of and the mechanisms underlying H3K27 methylation dysregulation.
-
Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] 2023年8月11日BACKGROUND: Intraductal papillary mucinous neoplasms (IPMNs) are a cystic precursor to pancreatic cancer. IPMNs deemed clinically to be at high-risk for malignant progression are frequently treated with surgical resection, and pathological examination of the pancreatectomy specimen is a key component of the clinical care of IPMN patients. METHODS: Systematic literature reviews were conducted around eight topics of clinical relevance in the examination of pathological specimens in patients undergoing resection of IPMN. RESULTS: This review provides updated perspectives on morphological subtyping of IPMNs, classification of intraductal oncocytic papillary neoplasms, nomenclature for high-grade dysplasia, assessment of T stage, distinction of carcinoma associated or concomitant with IPMN, role of molecular assessment of IPMN tissue, role of intraoperative assessment by frozen section, and preoperative evaluation of cyst fluid cytology. CONCLUSIONS: This analysis provides the foundation for data-driven approaches to several challenging issues in the pathology of IPMNs.
MISC
695-
Clinical Journal of Gastroenterology 9(1) 1-6 2016年2月1日Purpose: Endocrine cell carcinoma, according to the Japanese classification criteria for colorectal cancer, corresponds to neuroendocrine carcinoma (NEC) and mixed adenoneuroendocrine carcinoma (MANEC), as defined in the 2010 World Health Organization (WHO) classification. We retrospectively reviewed the clinical features of patients with these tumors diagnosed and treated at our institution. Methods: The clinicopathological features of endocrine cell carcinomas of the colon and rectum diagnosed by neuroendocrine markers from January 2000 to December 2012 were retrospectively evaluated in 12 patients. Results: Surgical specimens were obtained from eight of the 12 patients. MANEC was diagnosed in six patients and NEC in one. One tumor was unclassifiable. The tumors were not resected in four patients, and all died within 3 months. Of the eight patients who underwent resection, four received an R0 resection, two of whom underwent adjuvant chemotherapy and survived more than 5 years. One patient who underwent an R2 resection and continuous chemotherapy survived for 53 months. One patient with NEC underwent surgery and radiotherapy, and died 17 months later. Conclusion: Most endocrine cell carcinomas of the colon and rectum reviewed were MANECs. Though their prognosis was generally poor, chemotherapy may be effective in some patients.
-
日本肝胆膵外科学会学術集会プログラム・抄録集(CD-ROM) 28th ROMBUNNO.IP1‐2 2016年
-
膵臓 31(6) 818-824 2016年<p>日本膵臓学会発行の膵癌取扱い規約第7版において,病理診断に関連した主な改訂点は,局所進展度因子の判定基準の明確化,組織型分類の見直し,生検,細胞診の診断報告様式についての指針の新設,術前化学療法や放射線照射の組織学的な効果判定法の新設などである.膵腫瘍の診療において,膵癌取扱い規約はその診療方針決定における基盤でありまた診療科を越えた共通語でもある.したがって,腫瘍の病理組織型や病理診断の判定基準などについても,診療科を問わずその概要は知っておく必要がある.</p>
-
病理と臨床 34(1) 83-87 2016年1月
-
日本外科系連合学会誌 41(1) 52-57 2016年症例は76歳,女性.右季肋部痛を主訴に近医受診し,精査目的に当院紹介となった.上部内視鏡では胃体上部大彎に小陥凹病変を認め,生検で印環細胞癌と診断された.腹部造影CTにて胃周囲リンパ節の腫大と胃壁肥厚を認めた.リンパ節転移を伴う胃癌の診断で胃全摘術を施行した.術中所見で小腸間膜の一部に数個の結節を認めたため,摘出し病理検査へ提出した.最終診断は低分化型腺癌/印環細胞癌,pT1a(M),ly0,v0,n(18/69)(#4sa,#7,#8a,#10)であり,原病変は約10mm×10mmの胃粘膜内癌で潰瘍瘢痕はなかった.小腸間膜結節は胃癌の転移と診断された.腹膜播種をきたした胃粘膜内癌の極めて稀な1例を経験したので報告する.
-
臨床検査栃木 = Journal of Tochigi Society of Medical Technology : 栃木県臨床衛生検査技師会雑誌 11(2) 24-29 2016年
-
病理と臨床 34(1) 83-87 2016年1月
-
自治医科大学臨床検査技師年報 (38) 33-37 2016年1月63歳男。失神して救急搬送された。心肺停止蘇生後にCRT-D(心臓再同期療法+除細動機能)システムの埋め込みと同時の心筋生検を行った。病理組織所見では炎症細胞の浸潤や壊死、類上皮細胞、アミロイド沈着を疑う所見はなく、光顕的所見では細胞の淡明化と空胞状変化を認めた。また、透過型電子顕微鏡所見では筋原線維の萎縮、消失や層状ミエリン様構造を示すZebra like structure沈着を認め、Fabry病に類似した像であった。遺伝子検査や酵素活性の検査を行ったが、Fabry病やミトコンドリア心筋症は否定的であり、Fabry病に類似した原因不明の脂質沈着症と推測された。
-
自治医科大学臨床検査技師年報 (38) 38-41 2016年1月ThinPrep 5000を用いて扁平上皮細胞混在下における腺癌細胞の検出性能を検討した。陰性喀痰沈渣を混合した腺癌細胞の等倍希釈検査検体(x2〜x32)について、フィルター転写法による液状化検体細胞診(LBC法)を行い、腺癌細胞集塊の出現性と検出率を評価した。その結果、各希釈倍率および連続作製標本における腺癌細胞の検出率は、扁平上皮細胞混在下でも共存する細胞の影響を受けることなく13〜18%程度の一定の値を示した。また、腺癌細胞数の少ない高倍希釈(x32)検体では標本作製の連続操作によって集塊が減少し、フィルター転写法の原理である回転攪拌操作によって集塊が崩れた可能性が示された。
-
胆と膵 36(12) 1291-1297 2015年12月画像に反映され得る病理像として、肉眼レベルでは病変の形状、病変内部や境界部の性状があり、組織学的には、血管の増生、腫瘍細胞と線維組織のバランス、壊死、石灰沈着、膵萎縮、脂肪置換などがある。本稿では、画像(主にCT画像)に反映される病理組織学的な所見について概説する。(著者抄録)
-
胆と膵 36(12) 1291-1297 2015年12月画像に反映され得る病理像として、肉眼レベルでは病変の形状、病変内部や境界部の性状があり、組織学的には、血管の増生、腫瘍細胞と線維組織のバランス、壊死、石灰沈着、膵萎縮、脂肪置換などがある。本稿では、画像(主にCT画像)に反映される病理組織学的な所見について概説する。(著者抄録)
書籍等出版物
25共同研究・競争的資金等の研究課題
9-
日本学術振興会 科学研究費助成事業 基盤研究(C) 2023年4月 - 2026年3月
-
日本学術振興会 科学研究費助成事業 基盤研究(C) 2022年4月 - 2025年3月
-
日本学術振興会 科学研究費助成事業 基盤研究(C) 2020年4月 - 2024年3月
-
日本学術振興会 科学研究費助成事業 基盤研究(C) 2018年4月 - 2021年3月
-
日本学術振興会 科学研究費助成事業 基盤研究(C) 2017年4月 - 2020年3月