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Annual Report 2017

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 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 in pancreatic cancer is studied clinicopathologically and pathobiologically. We studied how to measure tumor-infiltrating immune cells in the small biopsied pancreatic cancer tissues and showed that more reliable results were obtained by qRT-PCR methods but not by immunohistochemistry.

Education

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

Future prospects

 We will respond the requests from the 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 currently analyzed qualitatively.

List of papers published in January 2017 - March 2018

Journal

 1. Mori T, Sukeda A, Sekine S, Shibata S, Ryo E, Okano H, Suzuki S, Hiraoka N. SOX10 Expression as Well as BRAF and GNAQ/11 Mutations Distinguish Pigmented Ciliary Epithelium Neoplasms From Uveal Melanomas. Invest Ophthalmol Vis Sci, 58:5445-5451, 2017

 2. Nagasato M, Rin Y, Yamamoto Y, Henmi M, Hiraoka N, Chiwaki F, Matsusaki K, Tagawa M, Sasaki H, Aoki K. A Tumor-targeting Adenovirus with High Gene-transduction Efficiency for Primary Pancreatic Cancer and Ascites Cells. Anticancer Res, 37:3599-3605, 2017

 3. Nakajima K, Heilbrun LK, Smith D, Hogan V, Raz A, Heath E. The influence of PSA autoantibodies in prostate cancer patients: a prospective clinical study-II. Oncotarget, 8:17643-17650, 2017

 4. Iwao Y, Ojima H, Kobayashi T, Kishi Y, Nara S, Esaki M, Shimada K, Hiraoka N, Tanabe M, Kanai Y. Liver atrophy after percutaneous transhepatic portal embolization occurs in two histological phases: Hepatocellular atrophy followed by apoptosis. World journal of hepatology, 9:1227-1238, 2017

 5. Yoshida H, Shimada K, Hiraoka N. Infrequent mismatch repair protein loss in gallbladder cancer patients in Japan. Virchows Arch, 470:109-112, 2017

 6. Shoji H, Tada K, Kitano S, Nishimura T, Shimada Y, Nagashima K, Aoki K, Hiraoka N, Honma Y, Iwasa S, Takashima A, Kato K, Boku N, Honda K, Yamada T, Heike Y, Hamaguchi T. The peripheral immune status of granulocytic myeloid-derived suppressor cells correlates the survival in advanced gastric cancer patients receiving cisplatin-based chemotherapy. Oncotarget, 8:95083-95094, 2017

 7. Iwasaki T, Nara S, Kishi Y, Esaki M, Shimada K, Hiraoka N. Surgical treatment of neuroendocrine tumors in the second portion of the duodenum: a single center experience and systematic review of the literature. Langenbecks Arch Surg, 402:925-933, 2017

 8. Cui L, Nakano K, Obchoei S, Setoguchi K, Matsumoto M, Yamamoto T, Obika S, Shimada K, Hiraoka N. Small Nucleolar Noncoding RNA SNORA23, Up-Regulated in Human Pancreatic Ductal Adenocarcinoma, Regulates Expression of Spectrin Repeat-Containing Nuclear Envelope 2 to Promote Growth and Metastasis of Xenograft Tumors in Mice. Gastroenterology, 153:292-306.e2, 2017

 9. Shimada Y, Kohno T, Ueno H, Ino Y, Hayashi H, Nakaoku T, Sakamoto Y, Kondo S, Morizane C, Shimada K, Okusaka T, Hiraoka N. An Oncogenic ALK Fusion and an RRAS Mutation in KRAS Mutation-Negative Pancreatic Ductal Adenocarcinoma. Oncologist, 22:158-164, 2017

10. Kihara A, Yoshida H, Watanabe R, Takahashi K, Kato T, Ino Y, Kitagawa M, Hiraoka N. Clinicopathologic Association and Prognostic Value of Microcystic, Elongated, and Fragmented (MELF) Pattern in Endometrial Endometrioid Carcinoma. Am J Surg Pathol, 41:896-905, 2017

11. Hayashi H, Kohno T, Ueno H, Hiraoka N, Kondo S, Saito M, Shimada Y, Ichikawa H, Kato M, Shibata T, Morizane C, Sakamoto Y, Shimada K, Komatsu Y, Sakamoto N, Okusaka T. Utility of Assessing the Number of Mutated KRAS, CDKN2A, TP53, and SMAD4 Genes Using a Targeted Deep Sequencing Assay as a Prognostic Biomarker for Pancreatic Cancer. Pancreas, 46:335-340, 2017

12. Nakajima K, Nangia-Makker P, Hogan V, Raz A. Cancer Self-Defense: An Immune Stealth. Cancer Res, 77:5441-5444, 2017

13. Sekine S, Ogawa R, Saito S, Ushiama M, Shida D, Nakajima T, Taniguchi H, Hiraoka N, Yoshida T, Sugano K. Cytoplasmic MSH2 immunoreactivity in a patient with Lynch syndrome with an EPCAM-MSH2 fusion. Histopathology, 70:664-669, 2017

14. Kishi Y, Nara S, Esaki M, Hiraoka N, Shimada K. Salvage hepatectomy for local recurrence of hepatocellular carcinomas offers survival comparable to that of matched patients who undergo primary hepatectomies. Eur J Surg Oncol, 43:1076-1082, 2017

15. Hironaka-Mitsuhashi A, Matsuzaki J, Takahashi RU, Yoshida M, Nezu Y, Yamamoto Y, Shiino S, Kinoshita T, Ushijima T, Hiraoka N, Shimizu C, Tamura K, Ochiya T. A tissue microRNA signature that predicts the prognosis of breast cancer in young women. PLoS One, 12:e0187638, 2017

16. Hashimoto T, Yamashita S, Yoshida H, Taniguchi H, Ushijima T, Yamada T, Saito Y, Ochiai A, Sekine S, Hiraoka N. WNT Pathway Gene Mutations Are Associated With the Presence of Dysplasia in Colorectal Sessile Serrated Adenoma/Polyps. Am J Surg Pathol, 41:1188-1197, 2017

17. Furukawa D, Chijiwa T, Matsuyama M, Mukai M, Matsuo EI, Nishimura O, Kawai K, Suemizu H, Nakagohri T, Ozawa S, Shimada K, Hiraoka N, Nakamura M. Plasma membrane expression of ZNF185 is a prognostic factor in pancreatic ductal carcinoma. Oncology letters, 14:3633-3640, 2017

18. Yamamoto Y, Nagasato M, Rin Y, Henmi M, Ino Y, Yachida S, Ohki R, Hiraoka N, Tagawa M, Aoki K. Strong antitumor efficacy of a pancreatic tumor-targeting oncolytic adenovirus for neuroendocrine tumors. Cancer Med, 6:2385-2397, 2017

19. Sekine S, Ogawa R, Hashimoto T, Motohiro K, Yoshida H, Taniguchi H, Saito Y, Yasuhiro O, Ochiai A, Hiraoka N. Comprehensive characterization of RSPO fusions in colorectal traditional serrated adenomas. Histopathology, 71:601-609, 2017

20. Sekine S, Mori T, Ogawa R, Tanaka M, Yoshida H, Taniguchi H, Nakajima T, Sugano K, Yoshida T, Kato M, Furukawa E, Ochiai A, Hiraoka N. Mismatch repair deficiency commonly precedes adenoma formation in Lynch Syndrome-Associated colorectal tumorigenesis. Mod Pathol, 30:1144-1151, 2017