Nishihara, Hiroshi



School of Medicine, Clinical and Translational Research Center Genomics Unit, Keio Cancer Center, Keio University Graduate School of Medicine (Shinanomachi)



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Contact Address

35 Shinanomachi, Shinjukuku, Tokyo, Japan

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Profile 【 Display / hide

  • 学 歴
    1995年(平成7年)3月 北海道大学医学部卒業(医学士)
    1999年(平成11年)3月 北海道大学大学院医学研究科 病理系専攻医学博士課程修了、学位取得(博士(医学))
    2002年(平成14年)3月 ~ 2004年(平成16年)7月
    Molecular pharmacology at University of California, San Diego, Department of Pharmacology (Dr. Paul A. Insel; as a research fellow)

    職 歴
    1999年(平成11年)4月 北海道大学医学部附属病院 病理部 (医員)
    2000年(平成12年)4月 北海道大学大学院医学研究科 分子細胞病理学 (助手)
    2008年(平成20年)10月 北海道大学大学院医学研究科 探索病理学講座 (特任准教授)
    2012年(平成24年)11月 北海道大学病院臨床研究開発センター 生体試料管理室 (室長(兼任))
    2015年(平成27年)1月 北海道大学大学院医学研究科探索病理学講座 (特任教授)
    2016年(平成28年)4月 北海道大学病院がん遺伝子診断部 (統括マネージャー(兼任))
    2017年(平成29年)4月 国立病院機構 北海道がんセンター がんゲノム医療センター(センター長)
    北海道大学病院 がん遺伝子診断部 客員教授(兼任;2018年3月まで)
    札幌医科大学医学部 客員教授(兼任;2019年3月まで)
         長崎大学医学部 客員教授(兼任)
    2017年(平成29年)7月 慶應義塾大学医学部 客員教授(兼任) 腫瘍センターゲノム医療ユニット  
    2017年(平成29年)11月 慶應義塾大学医学部 特任教授 腫瘍センターゲノム医療ユニット長
    社会医療法人北斗 北斗病院 病理・遺伝子診断科長(兼任)
    2018年(平成30年)10月 鹿児島大学医学部 客員教授(兼任)
    2019年(平成31年)4月  慶應義塾大学医学部 教授 臨床研究推進センター・腫瘍センターゲノム医療ユニット
    筑波大学医学部 客員教授(兼任)

Academic Background 【 Display / hide

  • 1989.04

    Hokkaido University, 医学部, 医学科

    University, Graduated, Master's course

  • 1995.04

    Hokkaido University, 大学院, 医学研究科

    Graduate School, Completed, Doctoral course

Academic Degrees 【 Display / hide

  • 博士(医学), Hokkaido University, Coursework, 1999.03

Licenses and Qualifications 【 Display / hide

  • 医師, 医師, 1995.04


Books 【 Display / hide

  • がんゲノム医療時代の分子腫瘍学

    西原, 広史, 文光堂, 2022.04,  Page: vii, 412p

  • がんゲノム病理学

    田中, 伸哉, 西原, 広史, 文光堂, 2021.11,  Page: vii, 225p

  • がんゲノム医療の最前線

    矢冨, 裕, 深川, 雅史, 滝川, 一, 武藤, 学, 宮地, 勇人, 西尾, 和人, 小川, 誠司, 西原, 広史, 秋田, 弘俊, 織田, 克利, 栗原, 友, H.U.グループホールディングス,ニッセイエブロ), 2021.07,  Page: 233p

Papers 【 Display / hide

  • Identifying intense inflammatory subtype of esophageal squamous cell carcinoma using clustering approach.

    Satoru Matsuda, Shota Hoshino, Tadahiro Goto, Hirofumi Kawakubo, Masashi Takeuchi, Ryota Kobayashi, Kohei Nakamura, Hiroya Takeuchi, Hiroshi Nishihara, Yuko Kitagawa

    General thoracic and cardiovascular surgery  2024.01


     View Summary

    OBJECTIVE: To establish a risk-stratification system for predicting the postoperative recurrence of esophageal squamous cell carcinoma, this study aimed to evaluate the prognostic value of clusters based on blood inflammation and coagulation markers and investigate their correlation with serum cytokines and genetic alteration. METHOD: This single-center, retrospective cohort study enrolled 491 patients with esophageal cancer who underwent subtotal esophagectomy between 2004 and 2012. For cluster exploration, nonhierarchical cluster analysis and k-means were applied using serum C-reactive protein, albumin, fibrinogen, and platelet-lymphocyte ratio as variables. Then, multivariate survival analysis was conducted to investigate the association of clusters with recurrence-free survival. To characterize the clusters, serum interleukin-6, interleukin-8, and genetic alteration in primary tumors, the PleSSision-Rapid panel, which can evaluate 160 representative driver genes, was used. RESULTS: Patients were classified into clusters 1, 2, and 3, which included 24 (5%), 161 (33%), and 306 (62%) patients, respectively. Compared with cluster 3, cluster 1 or 2 had significantly worse recurrence-free survival. Based on the multivariable analysis using cluster, pStage, and age as covariates, cluster was an independent prognostic factor for recurrence-free survival (hazard ratio, 1.55; 95% confidence interval, 1.08-2.21; P = 0.02). The percentage of serum interleukin-6 and interleukin-8 levels was the highest in cluster 1, followed by clusters 2 and 3. In 23 patients with available genomic profiles, no significant difference in representative genomic alterations was observed. CONCLUSIONS: Non-biased clustering using inflammation and coagulation markers identified the intense inflammatory subtype, which had an independent prognostic effect on recurrence-free survival.

  • Germline BRCA2 variant with low variant allele frequency detected in tumor-only comprehensive genomic profiling.

    Hideyuki Hayashi, Kei Kunimasa, Shigeki Tanishima, Kohei Nakamura, Marin Ishikawa, Yasutaka Kato, Eriko Aimono, Ryutaro Kawano, Hiroshi Nishihara

    Cancer science  2023.12


     View Summary

    Germline BRCA1/2 variants in comprehensive genomic profiling (CGP) often exhibit variant allele frequency (VAF) exceeding 50%. However, when genomic loss occurs at the ipsilateral allele, including the germline variant in tumor cells, the VAF is low. This case report presents a patient with uterine sarcoma with a pathogenic BRCA2 mutation and low VAF in tumor-only CGP, which was later identified as a germline variant. When genomic alterations in BRCA1/2 are identified in tumor-only CGP, the possible germline origin of the variants should be considered, even if their VAF is very low.

  • Eribulin inhibits growth of cutaneous squamous cell carcinoma cell lines and a novel patient-derived xenograft

    Che Yuan Hsu, Teruki Yanagi, Takuya Maeda, Hiroshi Nishihara, Kodai Miyamoto, Shinya Kitamura, Keiko Tokuchi, Hideyuki Ujiie

    Scientific Reports 13 ( 1 )  2023.12


     View Summary

    Advanced cutaneous squamous cell carcinoma (cSCC) is treated with chemotherapy and/or radiotherapy, but these typically fail to achieve satisfactory clinical outcomes. There have been no preclinical studies to evaluate the effectiveness of eribulin against cSCC. Here, we examine the effects of eribulin using cSCC cell lines and a novel cSCC patient-derived xenograft (PDX) model. In the cSCC cell lines (A431 and DJM-1 cells), eribulin was found to inhibit tumor cell proliferation in vitro as assessed by cell ATP levels. DNA content analysis by fluorescence-activated cell sorting (FACS) showed that eribulin induced G2/M cell cycle arrest and apoptosis. In xenograft models of cSCC cell lines, the administration of eribulin suppressed tumor growth in vivo. We also developed a cSCC patient-derived xenograft (PDX) which reproduces the histological and genetic characteristics of a primary tumor. Pathogenic mutations in TP53 and ARID2 were detected in the patient’s metastatic tumor and in the PDX tumor. The cSCC-PDX responded well to the administration of eribulin and cisplatin. In conclusion, the present study shows the promising antineoplastic effects of eribulin in cSCC. Also, we established a novel cSCC-PDX model that preserves the patient’s tumor. This PDX could assist researchers who are exploring innovative therapies for cSCC.

  • <i>BRCA1/2</i> reversion mutations in a pan‐cancer cohort

    Kohei Nakamura, Hideyuki Hayashi, Ryutaro Kawano, Marin Ishikawa, Eriko Aimono, Takaaki Mizuno, Hajime Kuroda, Yasuyuki Kojima, Naoki Niikura, Aya Kawanishi, Kei Takeshita, Shinsuke Suzuki, Shinichi Ueno, Kosuke Okuwaki, Jiichiro Sasaki, Masatoshi Yamaguchi, Kenta Masuda, Tatsuyuki Chiyoda, Wataru Yamagami, Chihiro Okada, Sachio Nohara, Shigeki Tanishima, Hiroshi Nishihara

    Cancer Science (Wiley)   2023.12

    Accepted,  ISSN  1347-9032

     View Summary


    Tumor sensitivity to platinum (Pt)‐based chemotherapy and poly(adenosine diphosphate ribose) polymerase (PARP) inhibitors is increased by homologous recombination deficiency‐causing mutations; in particular, reversion mutations cause drug resistance by restoring protein function. Treatment response is predicted by breast cancer susceptibility gene 1/2 (BRCA1/2) mutations; however, BRCA1/2 reversion mutations have not been comprehensively studied in pan‐cancer cohorts. We aimed to characterize BRCA1/2 reversion mutations in a large pan‐cancer cohort of Japanese patients by retrospectively analyzing sequencing data for BRCA1/2 pathogenic/likely pathogenic mutations in 3738 patients with 32 cancer types. We identified somatic mutations in tumors or circulating cell‐free DNA that could restore the ORF of adverse alleles, including reversion mutations. We identified 12 (0.32%) patients with somatic BRCA1 (n = 3) and BRCA2 (n = 9) reversion mutations in breast (n = 4), ovarian/fallopian tube/peritoneal (n = 4), pancreatic (n = 2), prostate (n = 1), and gallbladder (n = 1) cancers. We identified 21 reversion events—BRCA1 (n = 3), BRCA2 (n = 18)—including eight pure deletions, one single‐nucleotide variant, six multinucleotide variants, and six deletion–insertions. Seven (33.3%) reversion deletions showed a microhomology length greater than 1 bp, suggesting microhomology‐mediated end‐join repair. Disease course data were obtained for all patients with reversion events: four patients acquired mutations after PARP‐inhibitor treatment failure, two showed somatic reversion mutations after disease progression, following Pt‐based treatment, five showed mutations after both treatments, one patient with pancreatic cancer and BRCA1 reversion mutations had no history of either treatment. Although reversion mutations commonly occur in BRCA‐associated cancers, our findings suggest that reversion mutations due to Pt‐chemotherapy might be correlated with BRCA1/2‐mediated tumorigenesis even in non‐BRCA‐associated histologies.

  • Clinical availability and characteristics of multigene panel testing for recurrent/advanced gynecologic cancer.

    Shoko Kitazawa, Tatsuyuki Chiyoda, Kohei Nakamura, Kensuke Sakai, Tomoko Yoshihama, Hiroshi Nishio, Yusuke Kobayashi, Takashi Iwata, Kouji Banno, Wataru Yamagami, Hiroshi Nishihara, Daisuke Aoki

    International journal of clinical oncology  2023.08


     View Summary

    BACKGROUND: Japan's health insurance covers multigene panel testing. This study aimed to determine the potential availability and utility of gene panel testing clinically in gynecologic oncology. METHODS: We analyzed the characteristics of patients with gynecologic cancer who underwent gene panel testing using FoundationOne® CDx or OncoGuide™ NCC Oncopanel between November 2019 and October 2022. RESULTS: Out of 102 patients analyzed, 32, 18, 43, 8, and 1 had cervical, endometrial, ovarian cancers, sarcoma, and vaginal cancer, respectively. Druggable gene alteration was found in 70 patients (68.6%; 21 with cervical cancer, 15 with endometrial cancer, 28 with ovarian cancer, 5 with sarcoma, and 1 with other). The most common druggable gene alteration was PIK3CA mutation (n = 21), followed by PTEN mutation (n = 12) and high tumor mutation burden (TMB-H) (n = 11). TMB-H was detected in 5 patients with cervical cancer, 5 with endometrial cancer, and 1 with endometrial stromal sarcoma. Eleven patients (10.8%) received molecularly targeted therapy according to their gene aberrations. Gene panel testing was mostly performed when the second-line treatment was ineffective. Of all 102 patients, 60 did not have recommended treatment, and 15 died or had worsened conditions before obtaining the test results. CONCLUSION: Through multigene panel testing, although many patients had druggable gene alterations, 10.8% of them received the recommended treatment. TMB-H was mainly observed in cervical/endometrial cancer, suggesting its potential as a therapeutic biomarker of immune checkpoint inhibitors. Furthermore, patients' prognosis and performance status should be considered before performing the test.

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Papers, etc., Registered in KOARA 【 Display / hide

Reviews, Commentaries, etc. 【 Display / hide

  • 【がん遺伝子パネル検査と病理診断】症例提示 子宮内膜悪性腫瘍ならびに原発不明癌

    西原 広史

    病理と臨床 ((株)文光堂)  42 ( 1 ) 0065 - 0068 2024.01

    ISSN  0287-3745

  • 【臨床脳腫瘍学-最新の診断・治療と病態-】脳腫瘍の病理学 中枢神経系原発悪性リンパ腫

    西原 広史

    日本臨床 ((株)日本臨床社)  81 ( 増刊9 臨床脳腫瘍学 ) 100 - 104 2023.12

    ISSN  0047-1852

  • 【新しいバイオマーカーと分子標的治療の展開】核酸医薬

    谷口 博昭, 名取 幸和, 西原 広史, 今井 浩三

    腫瘍内科 ((有)科学評論社)  32 ( 4 ) 383 - 390 2023.10

    ISSN  1881-6568

  • CGP検査の結果により遺伝カウンセリング推奨となった胸部悪性腫瘍症例の考察

    福島 貴大, 寺井 秀樹, 中村 康平, 川野 竜太郎, 江本 桂, 石川 麻倫, 緒方 暁彦, 高岡 初誉, 齋藤 彩夏, 扇野 圭子, 安田 浩之, 川田 一郎, 副島 研造, 西原 広史, 福永 興壱

    肺癌 ((NPO)日本肺癌学会)  63 ( 5 ) 461 - 461 2023.10

    ISSN  0386-9628

  • LDT・RUOと保険診療 病理診断を目的とするがん遺伝子パネル検査のLDT運用の意義と課題について

    西原 広史

    日本臨床検査医学会誌 ((一社)日本臨床検査医学会)  71 ( 補冊 ) 037 - 037 2023.10

    ISSN  2436-2727

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Research Projects of Competitive Funds, etc. 【 Display / hide

  • Gene profiling for pressure ulcer


    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (B), Principal investigator

  • Clinical Sequence Platform for Brain Tumor


    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Principal investigator


Courses Taught 【 Display / hide