Yamazaki, Ken



School of Medicine, Department of Pathology (Shinanomachi)



External Links

Career 【 Display / hide

  • 2005.04

    Keio University School of Medicine


Research Areas 【 Display / hide

  • Molecular biology (Molecular Biology)

  • Cell biology (Cell Biology)

  • Experimental pathology (Experimental Pathology)

Research Keywords 【 Display / hide

  • cancer

  • gene expression profiling


Books 【 Display / hide

  • 癌と微小環境

    山﨑剣、真杉洋平、坂元亨宇, 羊土社, 2009.02

    Scope: 102-106

  • Japanese Journal of Diagnostic Imaging

    Fukuma M, Yamazaki K, Sakamoto M., 秀潤社, 2005.12

    Scope: 13-18

Papers 【 Display / hide

  • Diffuse and canalicular patterns of glypican-3 expression reflect malignancy of hepatocellular carcinoma

    Kawaida M., Yamazaki K., Tsujikawa H., Fukuma M., Abe Y., Kitago M., Shinoda M., Kitagawa Y., Sakamoto M.

    Pathology International (Pathology International)  69 ( 3 ) 125 - 134 2019.03

    Research paper (scientific journal), Accepted,  ISSN  13205463

     View Summary

    Glypican-3 (GPC3) is expressed in most hepatocellular carcinomas (HCCs). To investigate the significance of various GPC3 staining patterns in HCC, we classified 134 HCC patients into three groups: those with diffuse GPC3 staining, canalicular GPC3 staining, and others (including negative staining). HCCs with diffuse staining were correlated with poor differentiation, high Ki-67 indices, high serum α-fetoprotein (AFP) levels, and early recurrence. In contrast, HCCs with canalicular staining were well differentiated with lower AFP levels. Overall survival in this group was better than that of the other two groups. Comparative analysis of GPC3 staining patterns with markers for HCC subclassification showed that diffuse staining was correlated with the expression of biliary/stem cell markers, whereas canalicular staining was correlated with expression of the markers of WNT-activated HCCs. Induction of leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5), known as a target of the WNT signaling pathway, in HCC cells resulted in reduced GPC3 expression in vitro. The LGR5-induced cells formed tumors with canaliculus-like structures in mice and showed canalicular GPC3 staining. The current findings showed the significance of recognizing distinct GPC3 staining patterns, i.e., diffuse and canalicular, which may reflect different carcinogenetic mechanisms and indicate the level of malignancy of HCC.

  • Mesenchymal–epithelial transition of pancreatic cancer cells at perineural invasion sites is induced by Schwann cells

    Fujii-Nishimura Y., Yamazaki K., Masugi Y., Douguchi J., Kurebayashi Y., Kubota N., Ojima H., Kitago M., Shinoda M., Hashiguchi A., Sakamoto M.

    Pathology International (Pathology International)  68 ( 4 ) 214 - 223 2018.04

    Joint Work, Accepted,  ISSN  13205463

     View Summary

    © 2018 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd Epithelial–mesenchymal transition (EMT) promotes invasion and metastasis of pancreatic ductal adenocarcinoma (PDAC). However, the importance of its reverse process, mesenchymal–epithelial transition (MET), for PDAC remains unclear. We aimed to characterize the histological finding “focal differentiation” in PDAC at perineural invasion sites in the context of MET and to investigate the role of Schwann cells in inducing tumor MET. Tumor differentiation and immunohistochemical expressions of E-cadherin, SMAD3, and vimentin at perineural invasion sites were examined in 168 PDAC tissues. Four PDAC cell lines were co-cultured with Schwann cells to investigate cell morphology, motility, or EMT-related markers using immunocytochemistry and quantitative PCR. Of 168 tumors, 124 (74%) showed focal differentiation with enhanced E-cadherin membrane expression (P < 0.001) and decreased nuclear accumulation of SMAD3 (P < 0.001). Among 115 PDACs harboring grade 1/2 tumor, tumors with focal differentiation showed worse survival compared to those without focal differentiation (P = 0.019). PDAC cells co-cultured with Schwann cells demonstrated a sheet-like appearance, increased E-cadherin expression, decreased expressions of SMAD3 and vimentin, and reduced cell motility. In conclusion, MET-like change is induced by Schwann cells, suggesting that Schwann cells contribute to PDAC colonization in pancreatic nerves through activating the MET machinery inside tumor cells in the pancreatic tumor microenvironment.

  • Serum Wisteria Floribunda Agglutinin-Positive Sialylated Mucin 1 as a Marker of Progenitor/Biliary Features in Hepatocellular Carcinoma.

    Tamaki N, Kuno A, Matsuda A, Tsujikawa H, Yamazaki K, Yasui Y, Tsuchiya K, Nakanishi H, Itakura J, Korenaga M, Mizokami M, Kurosaki M, Sakamoto M, Narimatsu H, Izumi N.

    Scientific Reports 7 ( 244 )  2017.03

    Research paper (scientific journal), Joint Work, Accepted

  • Immunohistochemical molecular analysis indicates hepatocellular carcinoma subgroups that reflect tumor aggressiveness.

    Tsujikawa H, Masugi Y, Yamazaki K, Itano O, Kitagawa Y, Sakamoto M.

    Human Pathology 50   24 - 33 2016.04

    Research paper (scientific journal), Joint Work, Accepted

     View Summary

    Histopathologic parameters and molecular markers are widely accepted as useful predictors of tumor aggressiveness in hepatocellular carcinoma (HCC). However, few studies have analyzed immunohistochemical profiles comprehensively in one series, a fact that has resulted in fragmentation of information that could be applied in clinical practice. We conducted immunohistochemical expression analysis of biliary/stem cell markers (cytokeratin 19, sal-like protein 4, epithelial cell adhesion molecule, and CD133), Wnt/β-catenin signaling-related molecules (β-catenin and glutamine synthetase), p53, and cell proliferation markers (Ki-67 and mitosis) in 162 HCCs surgically resected from 142 patients and analyzed the results with respect to clinicopathological features. Immunohistochemical analysis broadly identified 3 groups: the biliary/stem cell marker-positive group, the Wnt/β-catenin signaling-related marker-positive group, and the biliary/stem cell marker-negative and Wnt/β-catenin signaling-related marker-negative group. p53 was frequently positive in the biliary/stem cell marker-positive group, but it was rarely positive in the Wnt/β-catenin signaling-related marker-positive group. The biliary/stem cell marker-positive group exhibited poor tumor differentiation, increased frequency of portal vein invasion and/or intrahepatic metastasis, and highly proliferative activity. In contrast, the biliary/stem cell marker-negative and Wnt/β-catenin signaling-related marker-negative group exhibited better tumor differentiation, a decreased frequency of portal vein invasion and/or intrahepatic metastasis, and less proliferative activity. The Wnt/β-catenin signaling-related marker-positive group showed neither tendency. The biliary/stem cell marker-positive group had the shortest time to recurrence among the 3 groups. Immunohistochemical profiling of HCC reflects tumor aggressiveness and suggests the potential efficacy of immunohistochemistry-based subclassification of HCC.

  • Overexpression of adenylate cyclase-associated protein 2 is a novel prognostic marker in malignant melanoma

    Masugi Y, Tanese K, Emoto K, Yamazaki K, Effendi K, Funakoshi T, Mori M, Sakamoto M

    Pathology International 65 ( 12 ) 627 - 634 2015.12

    Research paper (scientific journal), Joint Work, Accepted

display all >>

Presentations 【 Display / hide

  • Expression of mucin 1 reflects the malignancy of hepatocellular carcinoma.

    Ken Yamazaki, Yohei Masugi, Hanako Tsujikawa, Hidenori Ojima, Minoru Kitago, Masahiro Shinoda, Yuko Kitagawa, Michiie Sakamoto

    第77回日本癌学会学術総会 (大阪) , 2018.09, Oral Presentation(general)

  • Immunofluorescent digital slide technology to evaluate correlation between Glypican-3 expression and response to codrituzumab

    Takayoshi Tanaka, Yasuo Sugitani, Tokiya Abe, Miho Kawaida, Ken Yamazaki, Akinori Hashiguchi, Michiie Sakamoto, Toshihiko Ohtomo

    AACR 107th Annual Meeting 2016 (New Orleans, LA) , 2016.04, Poster (general)

     View Summary

    Background: Codrituzumab/GC33/RO5137382 is a recombinant humanized monoclonal antibody against Glypican-3 (GPC3) which is highly expressed in HCC cells. As part of phase I clinical trial, GC-002US study, evaluating escalating doses of codrituzumab plus sorafenib in HCC, immunofluorescent staining of GPC3 were applied in addition to GPC3 immunohistochemistry (IHC) with conventional DAB staining. The objectives of this work were to compare GPC3 expression levels by different staining methods and evaluate the correlation between these GPC3 scores and codrituzumab activities.

    Methods: Biopsies specimens (n = 34) collected at baseline in the phase I trial were evaluated by GPC3-IHC and immunofluorescent quantification digital slide (IQD) methods. GPC3-IHC were conducted using mouse anti-human GPC3 antibody, mouse GC33 (Ventana Medical Systems) as reported previously (Ikeda M. et al., Cancer Sci. 2014: 105; 455-462) and H scores were derived by two pathologists. For IQD, biopsy specimens were stained with same primary antibody, and were incubated with Qdot 655-conjugated secondary antibody. Fluorescent images of whole slides were obtained with the Nano-Zoomer (Hamamatsu Photonics K. K.). The IQD intensity score (immunofluorescent intensity per pixel) and cell score (immunofluorescent intensity per cell) were calculated respectively using MatLab (MathWorks Inc.).

    Results: There was a statistically significant correlation between GPC3 H scores and IQD scores. Among GPC3 scores, only the IQD cell score was correlated with serum GPC3 C-terminus increase by treatment (p = 0.032), whereas in the patients treated with higher dose of GC33 (≥ 10 mg/kg/week) the cytoplasmic H and the IQD intensity score were also correlated with serum GPC3 C-terminus increase by treatment. Interestingly, increasing cut-off values of IQD cell score levels led to lower HR and longer PFS. Best HR with lowest p value was observed at a cut-off value of 66,183 (HR = 0.24, p = 0.038).

    Conclusion: This study suggested that higher GPC3 expression on HCC cells quantified by IQD method was superior to other scores to predict codrituzumab activity, though this analysis was conducted only with limited number of subjects assessed. Further assessment and validation in clinical study of codrituzumab would be necessary to make a final conclusion on the clinical application of GPC3 IQD.

  • Up-regulation of integrin β4 promotes epithelial-mesenchymal transition and is a novel prognostic marker in pancreatic cancer.

    Masugi Y, Yamazaki K, Emoto K, Effendi K, Kitago M, Itano O, Kitagawa Y, Sakamoto M.

    AACR Annual Meeting 2014 (San Diego, CA) , 2014.04, Poster (general)

  • SMAD3 upregulation is a novel biomarker of poor prognosis and epithelial-mesenchymal transition in pancreatic cancer

    Yamazaki K, Masugi Y, Sakamoto M

    American Association for Cancer Research Annual Meeting 2013 (Washington DC) , 2013.04, Poster (general), American Association for Cancer Research

  • Adenylate cyclase-associated protein 1 promotes pancreatic cancer cell motility.

    Yamazaki K, Masugi Y, Sakamoto M

    第68回 日本癌学会学術総会 (横浜) , 2009.10, Oral Presentation(general)


Memberships in Academic Societies 【 Display / hide

  • 日本癌学会

  • 日本分子生物学会