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
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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.
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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.
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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.
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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.
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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-
日本臨床細胞学会雑誌 47(2) 504-504 2008年9月22日
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医学検査 : 日本臨床衛生検査技師会誌 = The Japanese journal of medical technology 57(8) 1063-1065 2008年8月25日症例は78歳男性で、血清クレアチニンの上昇前より尿細管上皮細胞を1〜9/HPFから10〜19/HPFの範囲で認めていた。また、尿細管上皮細胞は約2年間継続的に認められ、核が濃縮状で細胞の表面構造は不規則型顆粒状を呈し、中には細胞の大きさ100μm以上の顆粒円柱型や大型の鋸歯型の特殊型尿細管上皮細胞が観察された。剖検では拡張した尿細管腔を認め、尿沈渣検査と同様の円柱状の尿細管上皮細胞が確認された。尿細管上皮細胞の形態は尿細管腔の状態を反映し、特殊型尿細管上皮細胞の出現は尿細管腔の閉塞、或いは拡張を示唆する所見となる。尿沈渣から得られる細胞の形態所見は、病態解析の新たな付加的情報になると考えられた。
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外科 70(5) 476-482 2008年5月膵管内乳頭粘液性腫瘍(IPMN)と浸潤性膵管癌(IDC)は組織発生上の類似性がうかがわれるものの、完成された病変における臨床病理学的特徴には大きな相違がある。IDCの前駆病変と考えられている膵上皮内腫瘍性病変(PanIN)とIPMNの高異型度病変との分子レベルの違いは、SMAD4,MUC1,MUC2などにみられるが、低異型度病変では必ずしもその区別は明確ではない。それぞれの組織発生に関する知見を集積し、分子レベルでの両者の異同を明確にすることが、今後の新たな治療戦略につながるものと考えられる。(著者抄録)
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外科 70(5) 476-482 2008年5月
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外科 70(5) 476-482 2008年5月1日
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Diseases of the Pancreas: Current Surgical Therapy 497-511 2008年A thorough understanding of the pathology of the pancreas is critical to the proper surgical management of patients with pancreatic disease. Some neoplasms of the pancreas are entirely benign and can be managed conservatively, while others are highly lethal malignancies that are best treated by aggressive surgical resection. This chapter provides a broad overview of the pathology of pancreatic neoplasia with emphasis on features important for the surgical management of patients with pancreatic disease. Recent developments in our understanding of pancreatic neoplasia will also be discussed, particularly the growing recognition that a variety of noninvasive precursor lesions can give rise to invasive pancreatic cancer. These noninvasive precursor lesions create an opportunity to cure pancreatic neoplasia before an invasive cancer develops. At the same time they present a significant clinical management problem because there is precious little evidence-based medicine on which to judge when the benefit of removing a precursor lesion outweighs the risks of surgery. In this chapter we will broadly divide our discussion of neoplasms of the pancreas into a description of those with predominantly exocrine differentiation and those with predominantly endocrine differentiation. The discussion of exocrine neoplasms will be further subdivided into those that are cystic and those that are solid. © Springer-Verlag Berlin Heidelberg 2008.
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日本臨床細胞学会雑誌 46(1) 170-170 2007年3月22日
書籍等出版物
25共同研究・競争的資金等の研究課題
9-
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