Department of Morphology & Pathological Diagnosis, Clinical & Educational Collaboration Unit,
Faculty of Medical Sciences, Fujita Health University

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News & Topics

  • June 14, 2021
　Eleven fourth-year students have joined our group for graduation research
  • April 1, 2021
　In the new school term, two master’s students have joined our group.
  • March 14, 2021
　The graduation ceremony for 2020 was held. Congratulations to all graduate students!

Introduction

We aim to contribute to clinical medicine by providing undergraduate and graduate education in pathology and anatomy and conducting clinically relevant research, including the development of pathological diagnostic methods, improvement of laboratory techniques, and basic research on the mechanisms of disease onset and etiology. In addition, our laboratory has the aspect of a "clinical & educational collaboration unit." It aims to improve medical care, examination, education, and research through collaboration with the Department of Pathology of the Fujita Health University Hospital. As part of these efforts, we provide a "practical curriculum" in collaboration with the Department of Pathology as post-graduate education for graduate students who wish to become certified as cytoscreener. 

Members

Faculty members

Medical Technology

Graduate student

Master’s course: Syunpei Harada(M1)、Kaori Miura(M1)

Research Theme

Clinicopathological Diagnosis of Brain Tumors Indispensable for Patient’s Treatment

Brain tumors have many histological types in the WHO classification, and it is not uncommon for histopathological diagnosis to be complicated. In addition, malignant brain tumors such as glioblastoma are difficult to remove by surgery, are resistant to radiochemotherapy, and often have a poor prognosis. Analyzing brain tumors' growth potential, drug resistance, and genetic alteration will provide beneficial information indispensable for treating patients. For these analyzes, we are carrying out the following studies, mainly using immunohistochemical techniques.

Histological findings of malignant brain tumor (glioblastoma)

1) Examination of technical methods of immunostaining
2) Identification of the origins of tumor cells
3) Check of proliferative potential
4) Evaluation of drug tolerance to chemotherapy
5) Investigation of genetic alteration
(Masato Abe)

Carcinogenic mechanism of NDMA-induced renal tumorigenesis in SD and F344 rats

N-Nitrosodimethylamine (NDMA) is classified as Group 2A by the International Agency for Research on Cancer (IARC), and the World Health Organization (WHO) has set a guideline value of 100 ng/L for drinking water. The processing of foods, processed meat products, beer, and other malt liquors produce nitroso compounds, and nitrate and nitrite preservatives make NDMA. There are some reports of toxicity and carcinogenicity studies using laboratory animals. We have shown that a single intragastric administration shows that NDMA can cause renal tumors in SD male rats. In the future, we plan to use microRNAs, which are regulatory genes, to focus on the cancer-related RNAs and analyze the mechanism of toxicity and carcinogenicity.
(Takamasa Yanagida)

  • Renal cell carcinoma

  • Adenoma

Differentiation of Malignant Mesothelioma from Adenocarcinoma Cells Appearing in Body Fluid -Using Immunohistology and Electron Microscopy

Malignant mesothelioma is a malignant tumor occurring in the pleura, peritoneum, and pericardium and has been reported to be mainly caused by exposure to asbestos. When asbestos is released, it floats in the air for a long time, and when inhaled, it is deposited and accumulated in the alveoli. After a latent period of 20 to 40 years, malignant mesothelioma develops. The survival rate of malignant mesothelioma is about 20% after two years and about 3.7% after five years.
It can be difficult to differentiate malignant mesothelioma from adenocarcinoma cells or reactive mesothelial cells in body fluids. Therefore, we would like to examine the differentiation between adenocarcinoma cells and malignant mesothelioma cells appearing in body fluids using immunohistology, electron microscopy, and fluorescence in situ hybridization.
(Chiyuki Kaneko)

  • Malignant mesothelioma cells in pleural fluid

  • Electron Microscope Image of Malignant Mesothelioma<br />Nucleolus is clear

From the standpoint of pathology technologists, I have focused on developing "pathological techniques applicable to the routine work of pathological technologists.“ I specialize in improving pathological techniques, such as establishing highly sensitive in situ hybridization (Fig. 1) and ecological Grocott stain (Fig. 2). Currently, I am working on the following research project.

  • Figure 1: Highly sensitive in situ hybridization method for HCV detection

    There are no good marketed antibodies against HCV and it is currently difficult to prove by immunostaining. A highly sensitive in situ hybridization method combining LNA-DNA oligoprobe and tyramide sensitization can detect HCV.

  • Figure 2: Environmentally friendly Grocott dyeing

    The combination of heat treatment and periodic acid treatment enables the same level of dyeability as the conventional method without chromic acid.

１）Histochemistry of Neutrophil Extracellular Traps (NETs)

Histochemistry of Neutrophil Extracellular Traps (NETs)Neutrophil extracellular traps (NETs), which are reticular morphological changes of neutrophils, were initially regarded as a biological defense mechanism but are now attracting attention for their role in triggering various diseases. We have developed techniques for the immunohistochemical detection of NETs in FFPE sections and the prediction of differentiation between NETs and fibrin in HE-stained specimens (Fig. 3). Currently, we are promoting research that leads from pathological analysis to elucidation of various pathologic conditions.

２）Morphological and functional evaluation of bacterial vaginosis using cytological specimens

In routine cytological diagnosis, we tend to focus on the judgment of benign or malignant conditions while neglecting the diagnosis of infectious diseases. Gardnerella spp. is well known as the main bacteria involved in bacterial vaginosis, but some lactobacilli, known as good bacteria, can also affect vaginosis. We aim to establish a highly sensitive in situ hybridization method that can detect various bacteria and then clarify the involvement of bacteria in bacterial vaginosis and clue cell formation. Finally, we would establish new diagnostic criteria and feedback to cytological services.

３）Histochemistry of new cell death "necroptosis

Recently, a new cell death was discovered among necrosis, called necroptosis, which is controlled by specific molecules. It has been reported to be involved in cancer and inflammatory diseases, but there are still many unanswered questions. We will determine the relationship between necroptosis and various types of cell death (apoptosis, autophagy, NETs) in clinical samples of various diseases.

  • Figure 3-1: Differentiation between NETs and fibrin in HE-stained specimens (thin fibers).

    Most of the fine fibers are positive for NETs markers and negative for fibrin markers, thus identifying them as NETs. (Acute appendicitis)
    (Kazuya Shiogama)

  • Figure 3-2: Differentiation between NETs and fibrin in HE-stained specimens (thick fibers).

    Thick fibers indicate the coexistence of NETs and fibrin (NETs marker positive, fibrin marker positive) or fibrin (NETs marker negative, fibrin marker positive). (Upper row: Legionella pneumophila, Lower row: Liver abscess)

Organelles, represented by mitochondria, change their size and shape in response to the surrounding environment. Naturally, the cells formed by the myriad of variously shaped organelles each have their unique shape, and these cells form tissues and function as part of organs. To understand the pathogenesis of various diseases, we believe it is necessary to understand the complex hierarchical structure of living organisms in detail down to the nano-level, thus we are conducting ultrastructural analysis using the following morphological approaches.

  1. Seamless ultrastructure analysis by correlative light and electron microscopy
  2. Analysis of three-dimensional ultrastructure in paraffin sections by expansion microscopy

  • The workflow for optical microscopy to electron microscopy

    When we take an electron microscope image of the same spot taken with an optical microscope, we can simultaneously prove the ultrastructure and expression.

  • Nano-imaging of urinary tubules

    Expansion microscopy method allows optical microscopes to have a high resolution close to electron microscope images.

Academic Activities

Manuscripts

2021

  • Tsutsumi Y, Shiogama K, Sakurai K, Arase T, Domoto H: p16 immunostaining can avoid overdiagnosis in postmenopausal cervical cytology. IRJMMS. 9 (1): 1-8, 2021.
  • Yamada S, Muto J, Iba S, Shiogama K, Tsuyuki Y, Satou Akira, Ohba S, Murayama K, Sugita Y, Nakamura S, Yokoo H, Tomita A, Hirose Y, Tsukamoto T, Abe M: Primary central nervous system lymphomas with massive intratumoral hemorrhage: clinical, radiological, pathological and molecular evaluation of six cases. Neuropathology. https://doi.org/10.1111/neup.12739, 2021.
  • Shi H, Niimi A, Takeuchi T, Shiogama K, Mizutani Y, Kajino T, Inada K-I, Hase T, Hatta T, Shibata H, Fukui T, Chen‐Yoshikawa TF, Nagano K, Murate T, Kawamoto Y, Tomida S, Takahashi T, Suzuki M: CEBPγ facilitates lamellipodia formation and cancer cell migration through CERS6 upregulation. Cancer Sci. doi: 10.1111/cas.14928, 2021.
  • Li, C., Onouchi, T., Hirayama, M., Sakai, K., Matsuda, S., Yamada, N. O., & Senda, T. (2021). Morphological and functional abnormalities of hippocampus in APC1638T/1638T mice. Medical molecular morphology, 54(1), 31–40. https://doi.org/10.1007/s00795-020-00257-3
  • Yoshimitsu Y Katoh, Masaya Hirayama, Takanori Onouchi, Chiyuki Kaneko, Kazuyoshi Sakai, Masato Abe (2021). Necessity of glutaraldehyde-containing fixative to search for silver-positive bodies (nucleolus-like inclusion bodies) in the central nervous system cytoplasm. Journal of Analitical Bio-Science,44(3), 89-93.

2020

  • Shigeo Ohba, MD, PhD, Kazuhiro Murayama, MD, PhD, Kiyonori Kuwahara, MD, Eriel Sandika Pareira, MD, Shunsuke Nakae, MD, PhD, Yuya Nishiyama, MD, PhD, Kazuhide Adachi, MD, PhD, Seiji Yamada, MD, PhD, Hikaru Sasaki, MD, PhD, Naoki Yamamoto, MD, PhD, Masato Abe, MD, PhD, Joydeep Mukherjee, PhD, Mitsuhiro Hasegawa, MD, PhD, Russell O Pieper, PhD, Yuichi Hirose, MD, PhD, The Correlation of Fluorescence of Protoporphyrinogen IX and Status of Isocitrate Dehydrogenase in Gliomas, Neurosurgery, Volume 87, Issue 2, August 2020, Pages 408–417, https://doi.org/10.1093/neuros/nyz524
  • Takahashi, Y., Tsutsumi, Y., Takeuchi, C., Shiogama, K., Mizutani, Y., Inada, K. I., Yamamichi, N., & Koike, K. (2020). Nuclear staining of claudin-18 is a new immunohistochemical marker for diagnosing intramucosal well-differentiated gastric adenocarcinoma. Pathology international, 70(9), 644–652. https://doi.org/10.1111/pin.12978
  • Hiramatsu, N., Yamamoto, N., Isogai, S., Onouchi, T., Hirayama, M., Maeda, S., Ina, T., Kondo, M., & Imaizumi, K. (2020). An analysis of monocytes and dendritic cells differentiated from human peripheral blood monocyte-derived induced pluripotent stem cells. Medical molecular morphology, 53(2), 63–72. https://doi.org/10.1007/s00795-019-00231-8

2019

  • Ohba, S., Murayama, K., Nishiyama, Y., Adachi, K., Yamada, S., Abe, M., Hasegawa, M., & Hirose, Y. (2019). Clinical and Radiographic Features for Differentiating Solitary Fibrous Tumor/Hemangiopericytoma From Meningioma. World neurosurgery, 130, e383–e392. https://doi.org/10.1016/j.wneu.2019.06.094
  • Kuwahara, K., Ohba, S., Nakae, S., Hattori, N., Pareira, E. S., Yamada, S., Sasaki, H., Abe, M., Hasegawa, M., & Hirose, Y. (2019). Clinical, histopathological, and molecular analyses of IDH-wild-type WHO grade II–III gliomas to establish genetic predictors of poor prognosis. Brain tumor pathology, 36(4), 135-143. https://doi.org/10.1007/s10014-019-00348-9
  • Ohba, S., Yamada, Y., Murayama, K., Sandika, E., Sasaki, H., Yamada, S., Abe, M., Hasegawa, M., & Hirose, Y. (2019). c-Met Expression Is a Useful Marker for Prognosis Prediction in IDH-Mutant Lower-Grade Gliomas and IDH-Wildtype Glioblastomas. World neurosurgery, 126, e1042–e1049. https://doi.org/10.1016/j.wneu.2019.03.040
  • Sakaguchi, Y., Yamamichi, N., Tomida, S., Takeuchi, C., Kageyama-Yahara, N., Takahashi, Y., Shiogama, K., Inada, K. I., Ichinose, M., Fujishiro, M., & Koike, K. (2019). Identification of marker genes and pathways specific to precancerous duodenal adenomas and early stage adenocarcinomas. Journal of gastroenterology, 54(2), 131–140. https://doi.org/10.1007/s00535-018-1489-4
  • Okamura, S., Osaki, T., Nishimura, K., Ohsaki, H., Shintani, M., Matsuoka, H., Maeda, K., Shiogama, K., Itoh, T., & Kamoshida, S. (2019). Thymidine kinase-1/CD31 double immunostaining for identifying activated tumor vessels. Biotechnic & histochemistry : official publication of the Biological Stain Commission, 94(1), 60–64. https://doi.org/10.1080/10520295.2018.1499962
  • Hamed, M. A., Sayed, R. H., Shiogama, K., Eltaher, M. A., Suzuki, K., & Nakata, S. (2019). Localisation of basic fibroblast growth factor in cholesteatoma matrix: an immunochemical study. The Journal of laryngology and otology, 133(3), 183–186. https://doi.org/10.1017/S0022215119000112

Conference

2021

  • Masaya Hirayama, Takanori Onouchi, Kazuya Shiogama, Yoshimitsu Katoh, Kazuo Takahashi, Abe Masato Structural analysis of intracellular inclusion bodies localized in the paraventricular nucleus of the hypothalamus in normal mice The 53rd Annual Meeting of the Japanese Society for Clinical Molecular Morphology (to be announced in October)

2020

  • Ayano Michiba, Kazuya Shiogama, Masaya Hirayama, Seiji Yamada, Takanori Onouchi, Chiyuki Kaneko, Takamasa Yanagida, Tetsuya Tsukamoto, Masato Abe Tumor-associated macrophages (TAMs) are involved in the formation of macrophage extracellular traps (METs) in glioblastoma The 109th Annual Meeting of the Japanese Society of Pathology

Book

  • 水口國雄編集：染色法のすべて．医歯薬出版．p.47, 2021
  • 「臨床検査学入門」編集委員会：医学領域における臨床検査学入門第４版．KTC中央出版．2018
  • 標準理学療法学・作業療法学、病理学　第4版、医学書院、2017

Access

  • Access to Morphology & Pathology 314, 3rd  ⇒ University Building 3

Japanese Web Site