Department of Analytical Pathology

Nobuyoshi Hiraoka, Yoshinori Ino-Ishikawa

Introduction

In the Department of Analytical Pathology, the pathobiological and clinicopathological characteristics of the target molecules are analyzed for evaluating their potential significance in applying diagnostic or treatment use 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, or more effective analytical methods and tools.

Research activities

Tumor immune microenvironment is studied clinicopathologically and pathobiologically. Tertiary lymphoid organs (TLOs) are induced in various inflamed tissues. We showed that the presence and the frequency of TLOs in pancreatic cancer tissues were prognosticator. Tissue amino acid concentration profiles vary dynamically dependent on the metabolism in cells or tissues, which represent various biological processes. We investigated over 300 cases of various pancreatic tumors and showed that tissue amino acid profiles were useful for specifying tumor types, malignant phenotype, and tumor progression in pancreatic tumors.

Education

Teaching the analytical techniques to technicians and researchers in several departments of the National Cancer Center was performed.

Future prospects

We will answer requests from a selected project in various types of studies 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 2016

Journal

1.Fujimoto A, Furuta M, Totoki Y, Tsunoda T, Kato M, Shiraishi Y, Tanaka H, Taniguchi H, Kawakami Y, Ueno M, Gotoh K, Ariizumi S, Wardell CP, Hayami S, Nakamura T, Aikata H, Arihiro K, Boroevich KA, Abe T, Nakano K, Maejima K, Sasaki-Oku A, Ohsawa A, Shibuya T, Nakamura H, Hama N, Hosoda F, Arai Y, Ohashi S, Urushidate T, Nagae G, Yamamoto S, Ueda H, Tatsuno K, Ojima H, Hiraoka N, Okusaka T, Kubo M, Marubashi S, Yamada T, Hirano S, Yamamoto M, Ohdan H, Shimada K, Ishikawa O, Yamaue H, Chayama K, Miyano S, Aburatani H, Shibata T, Nakagawa H. Whole-genome mutational landscape and characterization of noncoding and structural mutations in liver cancer. Nat Genet, 48:500-509, 2016

2.Yachida S, Wood LD, Suzuki M, Takai E, Totoki Y, Kato M, Luchini C, Arai Y, Nakamura H, Hama N, Elzawahry A, Hosoda F, Shirota T, Morimoto N, Hori K, Funazaki J, Tanaka H, Morizane C, Okusaka T, Nara S, Shimada K, Hiraoka N, Taniguchi H, Higuchi R, Oshima M, Okano K, Hirono S, Mizuma M, Arihiro K, Yamamoto M, Unno M, Yamaue H, Weiss MJ, Wolfgang CL, Furukawa T, Nakagama H, Vogelstein B, Kiyono T, Hruban RH, Shibata T. Genomic Sequencing Identifies ELF3 as a Driver of Ampullary Carcinoma. Cancer Cell, 29:229-240, 2016

3.Hiraoka N, Ino Y, Yamazaki-Itoh R. Tertiary Lymphoid Organs in Cancer Tissues. Front Immunol, 7:244, 2016

4.Mitsuma K, Taniguchi H, Kishi Y, Hiraoka N. A case of adenocarcinoma with enteroblastic differentiation of the ampulla of Vater. Pathol Int, 66:230-235, 2016

5.Morofuji N, Ojima H, Hiraoka N, Okusaka T, Esaki M, Nara S, Shimada K, Kishi Y, Kondo T. Antibody-based proteomics to identify an apoptosis signature for early recurrence of hepatocellular carcinoma. Clin Proteomics, 13:28, 2016

6.Hori S, Shimada K, Ino Y, Oguro S, Esaki M, Nara S, Kishi Y, Kosuge T, Hattori Y, Sukeda A, Kitagawa Y, Kanai Y, Hiraoka N. Macroscopic features predict outcome in patients with pancreatic ductal adenocarcinoma. Virchows Arch, 469:621-634, 2016

7.Hori M, Onaya H, Hiraoka N, Yamaji T, Kobayashi H, Takahashi M, Mutoh M, Shimada K, Nakagama H. Evaluation of the degree of pancreatic fatty infiltration by area-based assessment of CT images: comparison with histopathology-based and CT attenuation index-based assessments. Jpn J Radiol, 34:667-676, 2016

8.Yoshida H, Shimada K, Kosuge T, Hiraoka N. A significant subgroup of resectable gallbladder cancer patients has an HER2 positive status. Virchows Arch, 468:431-439, 2016

9.Monma SE, Shimada K, Kishi Y, Nara S, Esaki M, Fujiki M, Miyamoto S, Hiraoka N. An extremely rare clinical manifestation of gallbladder cancer presenting with abdominal wall invasion with an erythematous skin break. Pathol Int, 66:302-304, 2016

10.Tada K, Maeshima AM, Hiraoka N, Yamauchi N, Maruyama D, Kim S-W, Watanabe T, Katayama N, Heike Y, Tobinai K, Kobayashi Y. Prognostic significance of HLA class I and II expression in patients with diffuse large B cell lymphoma treated with standard chemoimmunotherapy. Cancer Immunol Immunother, 65:1213-1222, 2016

11.Okamoto C, Yoshida H, Nakayama A, Kikuchi S, Ono N, Miyano H, Ino Y, Hiraoka N, Mizukoshi T. Determination of amino acids in human pancreas tissue sections using liquid chromatography tandem mass spectrometry. Chromatography, 37:125-132, 2016

12.Shiba S, Morizane C, Hiraoka N, Sasaki M, Koga F, Sakamoto Y, Kondo S, Ueno H, Ikeda M, Yamada T, Shimada K, Kosuge T, Okusaka T. Pancreatic neuroendocrine tumors: A single-center 20-year experience with 100 patients. Pancreatology, 16:99-105, 2016

13.Tada K, Kitano S, Shoji H, Nishimura T, Shimada Y, Nagashima K, Aoki K, Hiraoka N, Honma Y, Iwasa S, Okita N, Takashima A, Kato K, Yamada Y, Katayama N, Boku N, Heike Y, Hamaguchi T. Pretreatment Immune Status Correlates with Progression-Free Survival in Chemotherapy-Treated Metastatic Colorectal Cancer Patients. Cancer Immunol Res, 4:592-599, 2016