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Annual Report 2021

Department of Analytical Pathology

Nobuyoshi Hiraoka, Yoshinori Ino-Ishikawa, Chie Naito, Noriteru Doi, Chikashi Watase, Masanori Fuse, Utako Ishimoto, Patcharaporn Boottanun, Toshimitsu Iwasaki

Introduction

 In the Analytical Pathology Department, the pathobiological and clinicopathological characteristics of target molecules are analyzed to evaluate their potential significance for diagnostic or treatment applications in the future. Expression of the molecules or genes in human tissues is assessed by morphological techniques, immunohistochemistry, RT-PCR, in situ hybridization, etc., and the results are compared to clinicopathological information. We also try to develop new more reliable and more effective analytical methods and tools.

Research activities

 The tumor immune microenvironment in pancreatic cancer is studied clinicopathologically and pathobiologically. Effective neoadjuvant chemotherapy (NAT) causes tissue remodeling of pancreatic cancer (PDAC) with the alteration of the collagen molecules in the quality and quantity, which are often involved in the malignant characteristics. This suggests that effective NAT changes the extracellular matrix via collagen profiles through the interaction between cancer-associated fibroblasts and cancer cells via Ephrin-A5 and EphA2 interaction. We have also identified AQP1 and STRC as novel immunohistochemical markers of pancreatic serous neoplasms in pathological diagnosis. We have reported that the expressions of both core 3 O-glycan synthase and 6-sulfo N-acetyllactosamine on extended core 1 O-glycan are prognostic in patients with extrahepatic cholangiocarcinoma.

Education

 The analytical techniques were taught to technicians and researchers in several departments of the National Cancer Center.

Future Prospects

 We will answer requests regarding the selected project in various types of study containing basic, preclinical, and clinical studies, and assess the clinicopathological or pathobiological significance of the target molecules. We will develop methods of quantitative analysis to evaluate morphological findings that are currently analyzed qualitatively.

List of papers published in 2021

Journal

1. Nakajima K, Ino Y, Naito C, Nara S, Shimasaki M, Ishimoto U, Iwasaki T, Doi N, Esaki M, Kishi Y, Shimada K, Hiraoka N. Neoadjuvant therapy alters the collagen architecture of pancreatic cancer tissue via Ephrin-A5. British journal of cancer, 126:628-639, 2022

2. Takamizawa S, Morizane C, Tanabe N, Maruki Y, Kondo S, Hijioka S, Ueno H, Sugano K, Hiraoka N, Okusaka T. Clinical characteristics of pancreatic and biliary tract cancers associated with Lynch syndrome. Journal of hepato-biliary-pancreatic sciences, 29:377-384, 2022

3. Sawada J, Hiraoka N, Qi R, Jiang L, Fournier-Goss AE, Yoshida M, Kawashima H, Komatsu M. Molecular Signature of Tumor-Associated High Endothelial Venules That Can Predict Breast Cancer Survival. Cancer immunology research, 10:468-481, 2022

4. Watase C, Fuse M, Ino Y, Naito C, Hiraoka N. Novel insights into immunohistochemical analysis for diagnosing serous neoplasm of the pancreas: aquaporin 1, stereocilin, and transmembrane protein 255B. Histopathology, 79:872-879, 2021

5. Oishi T, Sasaki Y, Tong Y, Chen L, Onodera T, Iwasa S, Udo E, Furusato B, Fujimori H, Imamichi S, Honda T, Bessho T, Fukuoka J, Ashizawa K, Yanagihara K, Nakao K, Yamada Y, Hiraoka N, Masutani M. A newly established monoclonal antibody against ERCC1 detects major isoforms of ERCC1 in gastric cancer. Global health & medicine, 3:226-235, 2021

6. Boottanun P, Ino Y, Shimada K, Hiraoka N, Angata K, Narimatsu H. Association between the expression of core 3 synthase and survival outcomes of patients with cholangiocarcinoma. Oncology letters, 22:760, 2021

7. Capodanno Y, Chen Y, Schrader J, Tomosugi M, Sumi S, Yokoyama A, Hiraoka N, Ohki R. Cross-talk among MEN1, p53 and Notch regulates the proliferation of pancreatic neuroendocrine tumor cells by modulating INSM1 expression and subcellular localization. Neoplasia (New York, N.Y.), 23:979-992, 2021

8. Shibayama T, Makise N, Motoi T, Mori T, Hiraoka N, Yonemori K, Watanabe SI, Esaki M, Morizane C, Okuma T, Kawai A, Ushiku T, Yatabe Y, Yoshida A. Clinicopathologic Characterization of Epithelioid Hemangioendothelioma in a Series of 62 Cases: A Proposal of Risk Stratification and Identification of a Synaptophysin-positive Aggressive Subset. The American journal of surgical pathology, 45:616-626, 2021

9. Honda K, Hishiki T, Yamamoto S, Yamamoto T, Miura N, Kubo A, Itoh M, Chen WY, Takano M, Yoshikawa T, Kasamatsu T, Sonoda S, Yoshizawa H, Nakamura S, Itai Y, Shiota M, Koike D, Naya M, Hayakawa N, Naito Y, Matsuura T, Iwaisako K, Masui T, Uemoto S, Nagashima K, Hashimoto Y, Sakuma T, Matsubara O, Huang W, Ida T, Akaike T, Masugi Y, Sakamoto M, Kato T, Ino Y, Yoshida H, Tsuda H, Hiraoka N, Kabe Y, Suematsu M. On-tissue polysulfide visualization by surface-enhanced Raman spectroscopy benefits patients with ovarian cancer to predict post-operative chemosensitivity. Redox biology, 41:101926, 2021

10. Onishi Y, Kusumoto M, Motoi N, Hiraoka N, Sugawara S, Itou C, Sone M. Natural History of Epithelioid Hemangioendothelioma of the Liver: CT Findings of 15 Cases. Academic radiology, 28:778-782, 2021

11. Endo Y, Fujimoto M, Ito N, Takahashi Y, Kitago M, Gotoh M, Hiraoka N, Yoshida T, Kitagawa Y, Kanai Y, Arai E. Clinicopathological impacts of DNA methylation alterations on pancreatic ductal adenocarcinoma: prediction of early recurrence based on genome-wide DNA methylation profiling. Journal of cancer research and clinical oncology, 147:1341-1354, 2021