Tsujikawa, Hanako



School of Medicine, Division of Diagnostic Pathology (Shinanomachi)


Senior Assistant Professor (Non-tenured)/Assistant Professor (Non-tenured)

Career 【 Display / hide

  • 2006.04

    慶應義塾大学病院, 初期臨床研修医

  • 2008.08

    医学部総合医科学研究センター, 非常勤大学研究員(有期・文部科学省グローバルCOEプログラム「幹細胞医学のための研究拠点」)

  • 2008.09

    東京都清瀬小児病院, 非常勤職員

  • 2008.10

    永寿総合病院, 非常勤職員

  • 2010.05

    さいたま市立病院, 病理診断科, 非常勤職員

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Academic Background 【 Display / hide

  • 2000.04

    Fujita Health University, 医学部

    University, Graduated

  • 2008.04

    Keio University, 医学部, 医学科病理専攻

    Graduate School, Graduated, Doctoral course

Licenses and Qualifications 【 Display / hide

  • 医師免許, 2006.04

  • 死体解剖資格, 2012.03

  • 病理専門医, 2013.07

  • 細胞診専門医, 2013.12


Papers 【 Display / hide

  • Quantification of intratumoral collagen and elastin fibers within hepatocellular carcinoma tissues finds correlations with clinico-patho-radiological features

    Maehara J., Masugi Y., Abe T., Tsujikawa H., Kurebayashi Y., Ueno A., Ojima H., Okuda S., Jinzaki M., Shinoda M., Kitagawa Y., Oda Y., Honda H., Sakamoto M.

    Hepatology Research (Hepatology Research)  50 ( 5 ) 607 - 619 2020.05

    ISSN  13866346

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    © 2019 The Japan Society of Hepatology Aim: Emerging evidence suggests a promising role for tumor stromal factors in characterizing patients with various types of malignancies, including hepatocellular carcinoma (HCC). We quantified the amount of collagen and elastin fibers in HCC samples with the aim of clarifying the clinico-patho-radiological significance of fiber deposition in HCC. Methods: We computed the amount of collagen and elastin fibers using digital image analysis of whole-slide images of Elastica van Gieson-stained tissues from 156 surgically resected HCCs. Furthermore, we assessed the correlations between the fiber content of HCC samples and clinical, pathological, and radiological features, including immunohistochemistry-based molecular subtypes and immunosubtypes. Results: The intratumoral area ratio of collagen in HCC tissues (median 3.4%, range 0.1–22.2%) was more than threefold that of elastin (median 0.9%, range 0.1–9.0%); there was a strong positive correlation between the amounts of collagen and elastin. Higher levels of combined collagen and elastin were significantly associated with the confluent multinodular macroscopic tumor type, the absence of a fibrous capsule, intratumoral steatosis, scirrhous tumor stroma, dense inflammatory-cell infiltrates, and the biliary/stem cell markers-positive HCC subtype. The associations of higher collagen levels with radiological findings, including heterogeneous enhancement and persistent enhancement on dynamic computed tomography, were significant. In contrast, the associations of radiological findings with elastin fibers were not significant. Intratumoral fibrous stroma in HCC comprised septum-like and perisinusoidal fibrosis; these two forms represented distinct distribution patterns of fibers and fibroblasts. Conclusion: Quantitative analysis suggested that stromal fiber-rich HCCs likely represent a distinct clinico-patho-radiological entity.

  • Clinicopathological features of hepatocellular carcinoma with fatty change: Tumors with macrovesicular steatosis have better prognosis and aberrant expression patterns of perilipin and adipophilin

    Kubota N., Ojima H., Hatano M., Yamazaki K., Masugi Y., Tsujikawa H., Fujii-Nishimura Y., Ueno A., Kurebayashi Y., Shinoda M., Kitago M., Abe Y., Kitagawa Y., Sakamoto M.

    Pathology International (Pathology International)  70 ( 4 ) 199 - 209 2020.04

    ISSN  13205463

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    © 2020 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd The clinicopathological characteristics of steatosis in hepatocellular carcinoma (HCC) remain unclear. Here, we elucidate the features of macrovesicular steatosis (MaS) and microvesicular steatosis (MiS) in HCC and their relationships with background liver steatosis. A total of 165 HCC lesions were classified as MaS-HCC, MiS-HCC, or conventional HCC (cHCC) according to the cutoff value of 30% MaS or MiS in tumor cells. We analyzed the clinicopathological differences among these groups. MaS-HCC had less portal vein invasion, a higher proportion of HCC with intratumoral fibrosis, and a lower cumulative risk of recurrence than MiS-HCC or cHCC. Moreover, both MaS-HCC and MiS-HCC had lower incidences of hepatitis virus infection and higher levels of HbA1c than cHCC. Background liver steatosis was also higher in MaS-HCC than in cHCC. Immunohistochemical expression of perilipin (Plin1) and adipophilin (ADRP), major proteins expressed on lipid droplet membranes, revealed that almost all lipid droplets in HCC were Plin1 negative, whereas those in background liver were positive. In contrast, ADRP was expressed on lipid droplets in both HCC and background liver. We concluded that MaS-HCC and MiS-HCC were associated with metabolic abnormalities but exhibited different biologic behaviors. Furthermore, lipid droplets in HCC were pathophysiologically different from those in background liver.

  • Activation of extracellular signal-regulated kinase is associated with hepatocellular carcinoma with aggressive phenotypes

    Minagawa T., Yamazaki K., Masugi Y., Tsujikawa H., Ojima H., Hibi T., Abe Y., Yagi H., Kitago M., Shinoda M., Itano O., Kitagawa Y., Sakamoto M.

    Hepatology Research (Hepatology Research)  50 ( 3 ) 353 - 364 2020.03

    ISSN  13866346

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    © 2019 The Japan Society of Hepatology Aim: Sorafenib inhibits multiple kinase signaling pathways, including the rat sarcoma virus (Ras)/rapidly accelerated fibrosarcoma (Raf)/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway, and is a promising therapy for hepatocellular carcinoma (HCC). However, the role of ERK activation in HCC remains unclear. This study was designed to investigate the potential link between ERK activation and aggressive HCC phenotypes. Methods: We evaluated nuclear ERK expression by immunohistochemistry in 154 resected HCC nodules from 136 patients. We then investigated the associations of ERK expression with the clinicopathological characteristics of HCC, c-MET expression, and the molecular subclass biomarkers Ki-67, keratin 19 (KRT19, CK19, or K19), and sal-like protein 4. Multivariate Cox regression analysis was carried out to determine independent prognostic factors for overall survival and recurrence-free survival. The effects of ERK activation by hepatocyte growth factor (HGF) on eight HCC cell lines were further examined. Results: High-level nuclear expression of ERK was observed in 20 (13%) of 154 nodules and was significantly associated with higher serum alpha-fetoprotein levels (P = 0.034), poorer differentiation (P = 0.003), a higher Ki-67 index (P < 0.001), high-level expression of c-MET (P = 0.008), KRT19 (P = 0.002), or sal-like protein 4 (P < 0.001), and shorter overall survival (multivariate hazard ratio 3.448; P = 0.028) and recurrence-free survival (multivariate hazard ratio 2.755; P = 0.004). HCC cells treated with hepatocyte growth factor showed enhanced cell proliferation together with ERK activation and upregulated KRT19 expression, both of which were inhibited by sorafenib. Conclusions: High-level ERK activation is associated with a KRT19-positive highly proliferative subtype of HCC with a dismal prognosis. These findings support the key role of the hepatocyte growth factor/c-MET/ERK axis in HCC progression.

  • Precision pathology analysis of the development and progression of hepatocellular carcinoma: Implication for precision diagnosis of hepatocellular carcinoma

    Ueno A., Masugi Y., Yamazaki K., Kurebayashi Y., Tsujikawa H., Effendi K., Ojima H., Sakamoto M.

    Pathology International (Pathology International)  70 ( 3 ) 140 - 154 2020.03

    ISSN  13205463

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    © 2020 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd Outcomes for patients with hepatocellular carcinoma (HCC) remain poor because the condition is often unresponsive to the available treatments. Consequently, the early and precise diagnosis of HCC is crucial to achieve improvements in prognosis. For patients with chronic liver disease, the assessment of liver fibrosis is also important to ascertain both the staging of fibrosis and the risk of HCC occurrence. Early HCC was first described in 1991 in Japan and was defined internationally in 2009. As the concept of early HCC spread, the multistage hepatocarcinogenesis process became accepted. Consequently, improvements in imaging technology made the early diagnosis of HCC possible. At present, the most appropriate therapeutic strategy for HCC is determined using an integrated staging system that assesses the tumor burden, the degree of liver dysfunction and the patient performance status; however, pathological and molecular features are not taken into account. The recent introduction of several new therapeutic agents will change the treatment strategy for HCC. Against this background, HCC subclassification based on tumor cellular and microenvironmental characteristics will become increasingly important. In this review, we give an overview of how pathological analysis contributes to understanding the development and progression of HCC and establishing a precision diagnosis of HCC.

  • Pre-hepatectomy type IV collagen 7S predicts post-hepatectomy liver failure and recovery

    Ishii M., Itano O., Shinoda M., Kitago M., Abe Y., Hibi T., Yagi H., Takeuchi A., Tsujikawa H., Abe T., Kitagawa Y.

    World Journal of Gastroenterology (World Journal of Gastroenterology)  26 ( 8 ) 725 - 739 2020.02

    ISSN  10079327

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    ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved. BACKGROUND Liver resection is an effective treatment for benign and malignant liver tumors. However, a method for preoperative evaluation of hepatic reserve has not yet been established. Previously reported assessments of preoperative hepatic reserve focused only on liver failure in the early postoperative period and did not consider the long-term recovery of hepatic reserve. When determining eligibility for hepatectomy, the underlying pathophysiology needs to be considered to determine if the functional hepatic reserve can withstand both surgery and any postoperative therapy. AIM To identify pre-hepatectomy factors associated with both early postoperative liver failure and long-term postoperative liver function recovery. METHODS This study was a retrospective cohort study. We retrospectively investigated 215 patients who underwent hepatectomy at our hospital between May 2013 and December 2016. Early post-hepatectomy liver failure (PHLF) was defined using the International Study Group of Liver Surgery’s definition of PHLF. Long-term postoperative recovery of liver function was defined as the time taken for serum total bilirubin and albumin levels to return to levels of < 2 mg/dL and > 2.8 g/dL, respectively, and the time taken for Child-Pugh score to return to Child-Pugh class A. RESULTS Preoperative type IV collagen 7S was identified as a significant independent factor associated with both PHLF and postoperative long-term recovery of liver function. Further analysis revealed that the time taken for the recovery of Child-Pugh scores and serum total bilirubin and albumin levels was significantly shorter in patients with type IV collagen 7S ≤ 6 ng/mL than in those with type IV collagen 7S > 6 ng/mL. In additional analyses, similar results were observed in patients without chronic viral hepatitis associated with fibrosis. CONCLUSION Preoperative type IV collagen 7S is a preoperative predictor of PHLF and long-term postoperative liver function recovery. It can also be used in patients without chronic hepatitis virus.

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

Reviews, Commentaries, etc. 【 Display / hide

  • 【NAFLD/NASHの進歩と新たな展開】病理診断・基準の変遷、最新の状況

    入江 理恵, 辻川 華子, 坂元 亨宇

    消化器・肝臓内科 ((有)科学評論社)  7 ( 5 ) 432 - 437 2020.05

    ISSN  2432-3446

  • 肝細胞癌内の線維成分の組織学的定量解析と臨床病理放射線学的特徴との比較

    前原 純樹, 眞杉 洋平, 阿部 時也, 辻川 華子, 紅林 泰, 上野 彰久, 尾島 英知, 小田 義直, 本田 浩, 坂元 亨宇

    日本病理学会会誌 ((一社)日本病理学会)  109 ( 1 ) 294 - 294 2020.03

    ISSN  0300-9181

  • 肉腫成分が主体を占めた異所性子宮体部癌肉腫の一例

    鈴木 美那子, 照井 仁美, 鈴木 一生, 中島 清聖, 佐藤 孝之, 草刈 悟, 辻川 華子, 三上 修治, 早乙女 啓子, 山上 亘, 青木 大輔, 亀山 香織

    日本臨床細胞学会雑誌 ((公社)日本臨床細胞学会)  58 ( Suppl.2 ) 617 - 617 2019.10

    ISSN  0387-1193

  • 【NAFLD/NASH診療の現況と展望】NAFLD/NASHの病理所見(解説/特集)

    辻川 華子, 坂元 亨宇

    Pharma Medica 37 ( 9 ) 19 - 22 2019.09

    Article, review, commentary, editorial, etc. (scientific journal), Joint Work

  • 【NAFLD/NASH診療の現況と展望】NAFLD/NASHの病理所見

    辻川 華子, 坂元 亨宇

    Pharma Medica ((株)メディカルレビュー社)  37 ( 9 ) 19 - 22 2019.09

    ISSN  0289-5803

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Presentations 【 Display / hide

  • 肝細胞癌におけるインテグリンβ4発現の意義

    辻川 華子,山﨑 剣,真杉 洋平,坂元 亨宇

    第108回病理学会 (東京) , 


  • 肝細胞癌の免疫組織学的サブクラス分類

    辻川 華子,尾島 英知,坂元 亨宇

    第54回 肝癌研究会 (久留米) , 


  • Immunohistochemical subclassification of hepatocellular carcinoma

    辻川 華子,真杉 洋平,坂元 亨宇



  • 肝細胞癌の亜分類と個別化医療 免疫組織化学染色による肝細胞癌亜分類の試み

    Tsujikawa Hanako

    第51回肝臓学会 (熊本県) , 


    Symposium, workshop panel (public), 日本肝臓学会

  • 肝細胞癌におけるbiliary/stem cell markerの発現

    Tsujikawa Hanako

    第102回 日本病理学会総会 (北海道札幌市) , 


    Poster presentation, 日本病理学会

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

  • Standardization of histological diagnosis of NASH and pathological characteristics and tumor aggressiveness of NASH-related hepatocellular carcinoma


    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Early-Career Scientists , Principal investigator

  • 肝細胞癌サブクラス分類が悪性度を反映する機序の解明と診断への応用


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


Courses Taught 【 Display / hide










Memberships in Academic Societies 【 Display / hide

  • 日本癌学会, 

  • 日本病理学会

  • 日本肝癌研究会

  • 日本臨床細胞学会

  • 日本肝臓学会