Annual Report 2020

Division of Innovative Pathology and Laboratory Medicine (Tsukiji Campus)

Nobuyoshi Hiraoka, Kimihiko Kawamura, Sachiyo Hasegawa

Introduction

 In the Division of Innovative Pathology and Laboratory Medicine, we develop and improve new evaluation methods to analyze the pathobiological and clinicopathological characteristics of the molecules to be useful for clinical studies in EPOC projects.

Research activities

 Tumor immune microenvironment in pancreatic cancer is studied clinicopathologically and pathobiologically. Tumor infiltrating lymphocytes move from the regional lymph nodes to the tumor tissue via blood stream. Endothelial cells support extravasation of lymphocytes. We have found that endothelial cells in the cancer tissue have dysfunctional expressions of adhesion molecules resulting in decrement of tumor-infiltrating lymphocytes. This dysfunction is caused by abnormal TNFR1 signaling. We have identified novel compounds that can modulate TNFR1 signaling and promote tumor-infiltrating lymphocytes, thereby enhancing the antitumor immune response. We have also reported the clinicopathological significance of both classical and non-classical HLA class I antigens for pancreatic cancer.

Education

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

Future Prospects

 We will answer the requests from 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 2020

Journal

1. Ioka T, Furuse J, Fukutomi A, Mizusawa J, Nakamura S, Hiraoka N, Ito Y, Katayama H, Ueno M, Ikeda M, Sugimori K, Okano N, Shimizu K, Yanagimoto H, Okusaka T, Ozaka M, Todaka A, Nakamori S, Tobimatsu K, Sata N, Kawashima Y, Hosokawa A, Yamaguchi T, Miyakawa H, Hara H, Mizuno N, Ishii H. Randomized phase II study of chemoradiotherapy with versus without induction chemotherapy for locally advanced pancreatic cancer: Japan Clinical Oncology Group trial, JCOG1106. Jpn J Clin Oncol, 51:235-243, 2021

2. 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. J Cancer Res Clin Oncol, 147:1341-1354, 2021

3. 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 Biol, 41:101926, 2021

4. Iwasaki T, Nara S, Nishimura Y, Ueda H, Kishi Y, Esaki M, Shimada K, Hiraoka N. Postoperative acute multiple organ failure after hepatectomy in a Nigerian male with sickle cell trait: a case report. Surg Case Rep, 7:19, 2021

5. 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. Acad Radiol, 28:778-782, 2021

6. Bailey MH, Meyerson WU, Dursi LJ, Wang LB, Dong G, Liang WW, Weerasinghe A, Li S, Li Y, Kelso S, Saksena G, Ellrott K, Wendl MC, Wheeler DA, Getz G, Simpson JT, Gerstein MB, Ding L. Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples. Nat Commun, 11:4748, 2020

7. Li CH, Prokopec SD, Sun RX, Yousif F, Schmitz N, Boutros PC. Sex differences in oncogenic mutational processes. Nat Commun, 11:4330, 2020

8. Nakajima K, Ino Y, Yamazaki-Itoh R, Naito C, Shimasaki M, Takahashi M, Esaki M, Nara S, Kishi Y, Shimada K, Hiraoka N. IAP inhibitor, Embelin increases VCAM-1 levels on the endothelium, producing lymphocytic infiltration and antitumor immunity. Oncoimmunology, 9:1838812, 2020

9. Tian Y, Arai E, Makiuchi S, Tsuda N, Kuramoto J, Ohara K, Takahashi Y, Ito N, Ojima H, Hiraoka N, Gotoh M, Yoshida T, Kanai Y. Aberrant DNA methylation results in altered gene expression in non-alcoholic steatohepatitis-related hepatocellular carcinomas. J Cancer Res Clin Oncol, 146:2461-2477, 2020

10. Doi N, Ino Y, Angata K, Shimada K, Narimatsu H, Hiraoka N. Clinicopathological significance of core 3 O-glycan synthetic enzyme, β1,3-N-acetylglucosaminyltransferase 6 in pancreatic ductal adenocarcinoma. PLoS One, 15:e0242851, 2020

11. Hiraoka N, Nitta H, Ohba A, Yoshida H, Morizane C, Okusaka T, Nara S, Esaki M, Kishi Y, Shimada K. Details of human epidermal growth factor receptor 2 status in 454 cases of biliary tract cancer. Hum Pathol, 105:9-19, 2020

12. Noë M, Niknafs N, Fischer CG, Hackeng WM, Beleva Guthrie V, Hosoda W, Debeljak M, Papp E, Adleff V, White JR, Luchini C, Pea A, Scarpa A, Butturini G, Zamboni G, Castelli P, Hong SM, Yachida S, Hiraoka N, Gill AJ, Samra JS, Offerhaus GJA, Hoorens A, Verheij J, Jansen C, Adsay NV, Jiang W, Winter J, Albores-Saavedra J, Terris B, Thompson ED, Roberts NJ, Hruban RH, Karchin R, Scharpf RB, Brosens LAA, Velculescu VE, Wood LD. Genomic characterization of malignant progression in neoplastic pancreatic cysts. Nat Commun, 11:4085, 2020

13. Hiraoka N, Ino Y, Hori S, Yamazaki-Itoh R, Naito C, Shimasaki M, Esaki M, Nara S, Kishi Y, Shimada K, Nakamura N, Torigoe T, Heike Y. Expression of classical human leukocyte antigen class I antigens, HLA-E and HLA-G, is adversely prognostic in pancreatic cancer patients. Cancer Sci, 111:3057-3070, 2020

14. Morita S, Suda T, Kishi Y, Iwasaki T, Hiraoka N, Nagayama I, Hoshi T, Abe S, Yagi K, Hasegawa G, Ikarashi T, Terai S. Synchronous Double Bile Duct Cancers with Distinct Genetic Features. Intern Med, 59:2129-2134, 2020

15. Sato J, Kitano S, Motoi N, Ino Y, Yamamoto N, Watanabe S, Ohe Y, Hiraoka N. CD20+ tumor-infiltrating immune cells and CD204+ M2 macrophages are associated with prognosis in thymic carcinoma. Cancer Sci, 111:1921-1932, 2020