Department of Pathology and Clinical Laboratories

Atsushi Ochiai, Nobuyoshi Hiraoka, Shigeki Sekine, Hiromichi Matsushita, Noriko Motoi, Akiko Maeshima, Taisuke Mori, Hirokazu Taniguchi, Reiko Watanabe, Masayuki Yoshida, Akihiko Yoshida, Hiroshi Yoshida, Kaishi Satomi, Aoi Sukeda, Kuniko Sunami, Taiki Hashimoto, Kenichi Yoshida, Koko Mitsuma, Michiko Sugiyama, Naohiro Makise

Introduction

In the Pathology Division, the practice, education, and research of diagnostic and anatomic pathology were carried out. Diagnostic pathology practice comprises all issues on the processing of cell and tissue specimens obtained from patients, preparation of tissue blocks and pathology slides, and histological and cytopathological diagnoses of diseases. The practice of anatomic pathology consists of the autopsy, post-mortem systemic gross, and microscopic examination of patients. Case conferences with each clinical division were held periodically. Residents and trainees were accepted for training of diagnostic pathology on a rotating basis. To provide more accurate and informative diagnosis in future, staff members conduct basic, clinical, or translational research by themselves or in collaboration with other divisions or institutions.

The Clinical Laboratories Division provides an important service as an in-hospital diagnostic unit by examining laboratory specimens and screening for disorders. All laboratory data are provided for clinicians under strict internal and external quality control. The laboratories in this division have acquired the accreditation of ISO 15189, which certifies the quality and competence of a medical laboratory with regard to quality management and techniques, developed by the International Organization for Standardization's Technical Committee 212 (ISO/TC 212). In order to start a genome medicine where gene mutation profiles occurring in cancer tissues can contribute to select treatment options, a new genetic analyzing laboratory is established for performing comprehensive gene mutation analysis to clinical cancer samples using new-generation-sequencers under accreditation of semi- Clinical Laboratory Improvement Amendments (CLIA). The staff of the Clinical Laboratories Division will continuously work to improve the quality and quantity of laboratory services.

Routine activities

Pathology Division: In 2016, a total of 14 board-certified pathologists, four residents and 13 medical technologists, including nine cytotechnologists, cooperatively performed routine histological and cytopathological diagnosis of specimens obtained from patients at the National Cancer Center Hospital (NCCH), and education of the residents. Sixteen pathologists working exclusively in the NCCH also shared management of the division. We provided a total of 25,011 histological diagnoses consisting of 20,626 biopsy specimens including 2,193 intraoperative frozen sections and 4,385 surgically resected specimens, a total of cytopathological diagnoses of 12,722 patients including 433 for intraoperative diagnosis, and a total of 28 autopsies. We also provided a total of 200 pathological diagnoses for an outpatient clinic for pathology consultation (second opinion).

Clinical Laboratories Division: Fifty-one full-time and 11 part-time medical technologists, two photographers, and five assistants all provide services. These staff work in the sections of 1) general laboratory medicine and hematology, 2) biochemistry, 3) endocrinology, immunology, and tumor markers, 4) bacteriology, 5) genetic diagnostics, 6) transfusion, 7) phlebotomy, 8) physiological examination, and 9) pathology in the NCCH and in sections of phlebotomy and physiological examination in the Screening Center. Sections 1) to 5) are to be supervised by Drs. Hiromichi Matsushita and Kuniko Sunami, 6) and 7) by Dr. Saiko Kurosawa (Transfusion Therapy), 8) by Dr. Yasunori Mizuguchi (Diagnostic Radiology), Drs. Masaaki Shoji and Takeshi Iwasa (General Internal Medicine) and Dr. Eriko Iwamoto (Breast Surgery), and 9) by doctors in the Pathology Division. The bacteriology staff are members of the Infection Control Team and participate in the activities of infection management. The actual number of laboratory tests performed in this division in 2016 is shown in Table 2.

Research activities

1.Hepato-biliary pancreatic pathology

Table 1. Number of histopathological and cytopathological specimens diagnosed and autopsies

performed in the Pathology Division in 2016

We reported that tertiary lymphoid organs induced in cancer tissues are associated with the tumor immune microenvironment, cancer invasion, and the tissue structure of the cancer stroma. A case of ampullary adenocarcinoma with enteroblastic differentiation was reported.

2.Gastrointestinal pathology

Table 2. Number of laboratory tests examined in the Clinical Laboratories Division in 2016

Our mutational analysis of colorectal polyps revealed the frequent presence of PTPRK-RSPO3 fusions and RNF43 mutation as a characteristic genetic feature of traditional serrated adenomas. We also showed a significant correlation between age and mismatch repair deficiency among Lynch syndrome-associated colorectal adenomas.

3.Hematopathology

We reported clinicopathologic features of histologic transformation from MALT lymphoma to diffuse large B-cell lymphoma, and a case report of classical Hodgkin lymphoma primary refractory to anti-CD30 antibody therapy with transformation to CD30-positive diffuse large B-cell lymphoma. We contributed to analyses of double expression of cMYC and BCL2, and HLA class I and II for several subtypes of malignant lymphoma.

4.Thoracic pathology

Clinicopathological and genetic analysis was made on idiopathic pulmonary fibrosis associated non-small cell carcinomas. Clinical validated studies on primary adenocarcinoma's invasion factors, including spread through air space and invasion size of large lepidic adenocarcinoma related to outcome were performed. Giant lamellar bodies associated with adenocarcinoma of the lung were reported. We performed the immunohistochemical PD-L1 expression of lung and thymic cancer, and its clinical significance as collaboration studies.

5.Bone and soft tissue pathology

We successfully validated the usefulness of reduced SMARCB1 immunoexpression in the diagnosis of synovial sarcoma. Clinicopathological and immunohistochemical study of 20 round cell sarcomas with CIC gene rearrangement was performed, which clarified their distinctiveness as compared to EWSR1-rearranged Ewing sarcoma. We demonstrated that myxoid liposarcoma can rarely affect the retroperitoneum primarily. We proposed the utility of FOSL1 immunostaining for the diagnosis of desmoplastic fibroblastoma.

6.Breast pathology

We reported that the discordance in HR and HER2 status often occurred between primary and recurrent breast cancer, and had an independent prognostic impact in patients with recurrent breast cancer. We also investigated the risk factors for IBTR and CBTR in DCIS patients who underwent partial resection therapy.

7.Gynecological pathology

We participated in the international collaborative study on uterine carcinosarcoma and reported that histological pattern had impact on prognosis and response to chemotherapy in patients with uterine carcinosarcoma.

We also reported HER2 expression of uterine carcinosarcomas and a case of primary peritoneal carcinoma showing an unusual pattern of metastasis.

8.Head and Neck / Ophthalmic pathology

We examined 27 patients with maxillary malignant tumor to assess the impact of pathological status in orbital preservation surgery. From any microscopic orbital periosteum invasion was significance as a risk factor for orbital recurrence. A case of chondrosarcoma of the hyoid bone was reported.

9.Clinical Laboratories

An in-hospital bio-bank has been maintained for use by various researchers, and more than 650,000 post-clinical-test blood samples have been stored at -20 ℃ as of the end of 2016. Three sections of hematology, biochemistry and endocrinology, immunology and tumor markers, participated in the external quality control program endorsed by the Japanese Society of Laboratory Medicine. Some medical technologists found interesting findings in their routine practice and made presentations at several domestic medical assemblies. In the molecular diagnostic section, the mutation analyses of EGFR, and the chimeric gene detection of BCR-ABL1, RUNX1-RUNX1T1 and CBFB-MYH11 were provided as routine tests. In the cytogenetics section, using the Metafer system (an automated image analysis-assisted fluorescence in situ hybridization [FISH] system), the technique to evaluate the FISH imaging of the gene amplification of HER2 and the gene rearrangement of DDIT3, EWSR1, and SS18 were established and maintained. These two sections provided data not only for clinical practices but also for research activities of doctors in the NCCH and/or the National Cancer Center Research Institute (NCCRI).

List of papers published in 2016

Journal

1.Akaike G, Ueno T, Matsumoto S, Motoi N, Matsueda K. Rapidly growing giant cell tumor of bone in a skeletally immature girl. Skeletal Radiol, 45:567-573, 2016

2.Amaki J, Matsushita H, Kitamura Y, Nagao R, Murayama H, Kojima M, Ando K. The formation of an aberrant PAX5 transcript in a patient with mixed phenotype acute leukemia harboring der(9)t(7;9)(q11.2;p13). Leuk Res Rep, 5:14-17, 2016

3.Araki T, Takashima A, Hamaguchi T, Honma Y, Iwasa S, Okita N, Kato K, Yamada Y, Hashimoto H, Taniguchi H, Kushima R, Nakao K, Boku N, Shimada Y. Amrubicin in patients with platinum-refractory metastatic neuroendocrine carcinoma and mixed adenoneuroendocrine carcinoma of the gastrointestinal tract. Anticancer Drugs, 27:794-799, 2016

4.Asao T, Fujiwara Y, Sunami K, Kitahara S, Goto Y, Kanda S, Horinouchi H, Nokihara H, Yamamoto N, Ichikawa H, Kohno T, Tsuta K, Watanabe S, Takahashi K, Ohe Y. Medical treatment involving investigational drugs and genetic profile of thymic carcinoma. Lung Cancer, 93:77-81, 2016

5.Chino A, Nagayama S, Ishikawa H, Morishige K, Kishihara T, Arai M, Sugiura Y, Motoi N, Yamamoto N, Tamegai Y, Igarashi M. Cancer emerging from the recurrence of sessile serrated adenoma/polyp resected endoscopically 5 years ago. Jpn J Clin Oncol, 46:89-95, 2016

6.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

7.Hayakawa K, Matsumoto S, Ae K, Tanizawa T, Gokita T, Funauchi Y, Motoi N. Risk factors for distant metastasis of dermatofibrosarcoma protuberans. J Orthop Traumatol, 17:261-266, 2016

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

9.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

10.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

11.Horii R, Honma N, Ogiya A, Kozuka Y, Yoshida K, Yoshida M, Horiguchi S, Ito Y, Mukai H. The Japanese Breast Cancer Society clinical practice guidelines for pathological diagnosis of breast cancer, 2015 edition. Breast Cancer, 23:391-399, 2016

12.Horiike A, Takeuchi K, Uenami T, Kawano Y, Tanimoto A, Kaburaki K, Tambo Y, Kudo K, Yanagitani N, Ohyanagi F, Motoi N, Ishikawa Y, Horai T, Nishio M. Sorafenib treatment for patients with RET fusion-positive non-small cell lung cancer. Lung Cancer, 93:43-46, 2016

13.Inoki K, Nakajima T, Sekine S, Sugano K, Tsukamoto S, Yamada M, Mutoh M, Sakamoto T, Matsuda T, Sekiguchi M, Ushiama M, Yoshida T, Sakamoto H, Kanemitsu Y, Saito Y. Depressed-type submucosal invasive colorectal cancer in a patient with Lynch syndrome diagnosed using short-interval colonoscopy. Dig Endosc, 28:749-754, 2016

14.Ishiguro T, Sato A, Ohata H, Ikarashi Y, Takahashi R-U, Ochiya T, Yoshida M, Tsuda H, Onda T, Kato T, Kasamatsu T, Enomoto T, Tanaka K, Nakagama H, Okamoto K. Establishment and characterization of an in vitro model of ovarian cancer stem-like cells with an enhanced proliferative capacity. Cancer Res, 76:150-160, 2016

15.Kakinuma R, Noguchi M, Ashizawa K, Kuriyama K, Maeshima AM, Koizumi N, Kondo T, Matsuguma H, Nitta N, Ohmatsu H, Okami J, Suehisa H, Yamaji T, Kodama K, Mori K, Yamada K, Matsuno Y, Murayama S, Murata K. Natural History of Pulmonary Subsolid Nodules: A Prospective Multicenter Study. J Thorac Oncol, 11:1012-1028, 2016

16.Kamino H, Nakamura Y, Tsuneki M, Sano H, Miyamoto Y, Kitamura N, Futamura M, Kanai Y, Taniguchi H, Shida D, Kanemitsu Y, Moriya Y, Yoshida K, Arakawa H. Mieap-regulated mitochondrial quality control is frequently inactivated in human colorectal cancer. Oncogenesis, 4:e181, 2016

17.Kanda H, Furuta R, Motoi N, Suzuki N, Furuta N, Komatsu K, Sugiyama Y, Saiura A, Sugitani M, Ishikawa Y. Touch cytology smear of an inflammatory hepatocellular adenoma displaying an unusual pattern: A case report. Diagn Cytopathol, 44:1074-1077, 2016

18.Kanda S, Goto K, Shiraishi H, Kubo E, Tanaka A, Utsumi H, Sunami K, Kitazono S, Mizugaki H, Horinouchi H, Fujiwara Y, Nokihara H, Yamamoto N, Hozumi H, Tamura T. Safety and efficacy of nivolumab and standard chemotherapy drug combination in patients with advanced non-small-cell lung cancer: a four arms phase Ib study. Ann Oncol, 27:2242-2250, 2016

19.Katayama R, Sakashita T, Yanagitani N, Ninomiya H, Horiike A, Friboulet L, Gainor JF, Motoi N, Dobashi A, Sakata S, Tambo Y, Kitazono S, Sato S, Koike S, John Iafrate A, Mino-Kenudson M, Ishikawa Y, Shaw AT, Engelman JA, Takeuchi K, Nishio M, Fujita N. P-glycoprotein Mediates Ceritinib Resistance in Anaplastic Lymphoma Kinase-rearranged Non-small Cell Lung Cancer. EBioMedicine, 3:54-66, 2016

20.Kawai H, Matsushita H, Ohmachi K, Kojima M, Machida S, Ogawa Y, Kawada H, Nakamura N, Ando K. Four hepatosplenic T-cell lymphoma cases of Japanese patients. Leuk Res Rep, 5:3-6, 2016

21.Kawajiri A, Maruyama D, Maeshima AM, Nomoto J, Makita S, Kitahara H, Miyamoto KI, Fukuhara S, Suzuki T, Munakata W, Tajima K, Itami J, Taniguchi H, Kobayashi Y, Tobinai K. Impact of the double expression of MYC and BCL2 on outcomes of localized primary gastric diffuse large B-cell lymphoma patients in the rituximab era. Blood Cancer J, 6:e477, 2016

22.Kobayashi K, Matsumoto F, Kodaira M, Mori T, Murakami N, Yoshida A, Maki D, Teshima M, Fukasawa M, Itami J, Asai M, Yoshimoto S. Significance of delayed primary excision in localized nonmetastatic adult head and neck rhabdomyosarcoma. Cancer Med, 5:2708-2714, 2016

23.Kojima M, Ogiya D, Ichiki A, Hara R, Amaki J, Kawai H, Numata H, Sato A, Miyamoto M, Suzuki R, Machida S, Matsushita H, Ogawa Y, Kawada H, Ando K. Refractory acute promyelocytic leukemia successfully treated with combination therapy of arsenic trioxide and tamibarotene: A case report. Leuk Res Rep, 5:11-13, 2016

24.Kurihara H, Shimizu C, Miyakita Y, Yoshida M, Hamada A, Kanayama Y, Yonemori K, Hashimoto J, Tani H, Kodaira M, Yunokawa M, Yamamoto H, Watanabe Y, Fujiwara Y, Tamura K. Molecular imaging using PET for breast cancer. Breast Cancer, 23:24-32, 2016

25.Kuroda H, Sakao Y, Mun M, Motoi N, Ishikawa Y, Nakagawa K, Yatabe Y, Okumura S. Therapeutic value of lymph node dissection for right middle lobe non-small-cell lung cancer. J Thorac Dis, 8:795-802, 2016

26.Maeshima AM, Taniguchi H, Toyoda K, Yamauchi N, Makita S, Fukuhara S, Munakata W, Maruyama D, Kobayashi Y, Tobinai K. Clinicopathological features of histological transformation from extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue to diffuse large B-cell lymphoma: an analysis of 467 patients. Br J Haematol, 174:923-931, 2016

27.Makita S, Maeshima AM, Taniguchi H, Kitahara H, Fukuhara S, Munakata W, Suzuki T, Maruyama D, Kobayashi Y, Tobinai K. Classical Hodgkin lymphoma primary refractory to brentuximab vedotin, with transformation to CD30-positive diffuse large B-cell lymphoma. Int J Hematol, 104:396-399, 2016

28.Makita S, Maruyama D, Maeshima AM, Taniguchi H, Miyamoto K, Kitahara H, Fukuhara S, Munakata W, Kobayashi Y, Itami J, Tobinai K. Clinical features and outcomes of 139 Japanese patients with Hodgkin lymphoma. Int J Hematol, 104:236-244, 2016

29.Masai K, Tsuta K, Motoi N, Shiraishi K, Furuta K, Suzuki S, Asakura K, Nakagawa K, Sakurai H, Watanabe S, Hiraoka N, Asamura H. Clinicopathological, Immunohistochemical, and Genetic Features of Primary Lung Adenocarcinoma Occurring in the Setting of Usual Interstitial Pneumonia Pattern. J Thorac Oncol, 11:2141-2149, 2016

30.Matsumoto M, Nakajima T, Kakugawa Y, Sakamoto T, Kuribayashi S, Otake Y, Matsuda T, Kanemitsu Y, Taniguchi H, Saito Y. Surveillance using capsule endoscopy is safe in post-colectomy patients with familial adenomatous polyposis: a prospective Japanese study. Fam Cancer, 15:75-83, 2016

31.Matsuo K, Takazawa Y, Ross MS, Elishaev E, Podzielinski I, Yunokawa M, Sheridan TB, Bush SH, Klobocista MM, Blake EA, Takano T, Matsuzaki S, Baba T, Satoh S, Shida M, Nishikawa T, Ikeda Y, Adachi S, Yokoyama T, Takekuma M, Fujiwara K, Hazama Y, Kadogami D, Moffitt MN, Takeuchi S, Nishimura M, Iwasaki K, Ushioda N, Johnson MS, Yoshida M, Hakam A, Li SW, Richmond AM, Machida H, Mhawech-Fauceglia P, Ueda Y, Yoshino K, Yamaguchi K, Oishi T, Kajiwara H, Hasegawa K, Yasuda M, Kawana K, Suda K, Miyake TM, Moriya T, Yuba Y, Morgan T, Fukagawa T, Wakatsuki A, Sugiyama T, Pejovic T, Nagano T, Shimoya K, Andoh M, Shiki Y, Enomoto T, Sasaki T, Mikami M, Shimada M, Konishi I, Kimura T, Post MD, Shahzad MM, Im DD, Yoshida H, Omatsu K, Ueland FR, Kelley JL, Karabakhtsian RG, Roman LD. Significance of histologic pattern of carcinoma and sarcoma components on survival outcomes of uterine carcinosarcoma. Ann Oncol, 27:1257-1266, 2016

32.Matsushita H, Maruyama D. Bone marrow involvement of primary cutaneous gamma/delta T-cell lymphoma. Blood, 128:2274, 2016

33.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

34.Miyamoto K, Kobayashi Y, Maeshima AM, Taniguchi H, Nomoto J, Kitahara H, Fukuhara S, Munakata W, Maruyama D, Tobinai K. Clinicopathological prognostic factors of 24 patients with B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma. Int J Hematol, 103:693-702, 2016

35.Mizutani R, Imamachi N, Suzuki Y, Yoshida H, Tochigi N, Oonishi T, Akimitsu N. Oncofetal protein IGF2BP3 facilitates the activity of proto-oncogene protein eIF4E through the destabilization of EIF4E-BP2 mRNA. Oncogene, 35:3495-3502, 2016

36.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

37.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

38.Murakami N, Matsumoto F, Yoshimoto S, Ito Y, Mori T, Ueno T, Tuchida K, Kashihara T, Kobayashi K, Harada K, Kitaguchi M, Sekii S, Umezawa R, Takahashi K, Inaba K, Igaki H, Itami J. Patterns of recurrence after selective postoperative radiation therapy for patients with head and neck squamous cell carcinoma. BMC Cancer, 16:192, 2016

39.Nagao R, Kikuti YY, Carreras J, Kikuchi T, Miyaoka M, Matsushita H, Kojima M, Ando K, Sakata-Yanagimoto M, Chiba S, Nakamura N. Clinicopathologic Analysis of Angioimmunoblastic T-cell Lymphoma With or Without RHOA G17V Mutation Using Formalin-fixed Paraffin-embedded Sections. Am J Surg Pathol, 40:1041-1050, 2016

40.Nakano K, Motoi N, Tomomatsu J, Gokita T, Ae K, Tanizawa T, Matsumoto S, Takahashi S. Risk factors for pneumothorax in advanced and/or metastatic soft tissue sarcoma patients during pazopanib treatment: a single-institute analysis. BMC Cancer, 16:750, 2016

41.Ogiya D, Matsushita H, Murayama H, Ando K. Chediak-Higashi-like granules and waxy Auer bodies in a case of acute promyelocytic leukemia. Int J Hematol, 104:637-638, 2016

42.Ohtomo-Oda R, Komatsu S, Mori T, Sekine S, Hirajima S, Yoshimoto S, Kanai Y, Otsuji E, Ikeda E, Tsuda H. SMYD2 overexpression is associated with tumor cell proliferation and a worse outcome in human papillomavirus-unrelated nonmultiple head and neck carcinomas. Hum Pathol, 49:145-155, 2016

43.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

44.Okamura T, Izumo T, Yagishita H, Mori T, Sakamoto K, Harada K. Disordered arrangements of basal cells as a prognostic factor for oral epithelial dysplasia: a morphometric study of 96 cases. Oral Surg Oral Med Oral Pathol Oral Radiol, 122:355-361, 2016

45.Onizuka M, Matsushita H, Machida S, Toyosaki M, Amaki J, Aoyama Y, Miyamoto M, Ando K. Bacterial Pneumonia-induced Persistent Remission of Severe Immune Thrombocytopenia after Allogeneic Hematopoietic Stem Cell Transplantation. Intern Med, 55:179-183, 2016

46.Rokutan H, Hosoda F, Hama N, Nakamura H, Totoki Y, Furukawa E, Arakawa E, Ohashi S, Urushidate T, Satoh H, Shimizu H, Igarashi K, Yachida S, Katai H, Taniguchi H, Fukayama M, Shibata T. Comprehensive mutation profiling of mucinous gastric carcinoma. J Pathol, 240:137-148, 2016

47.Saito Y, Nagae G, Motoi N, Miyauchi E, Ninomiya H, Uehara H, Mun M, Okumura S, Ohyanagi F, Nishio M, Satoh Y, Aburatani H, Ishikawa Y. Prognostic significance of CpG island methylator phenotype in surgically resected small cell lung carcinoma. Cancer Sci, 107:320-325, 2016

48.Sasaki Y, Hamaguchi T, Yamada Y, Takahashi N, Shoji H, Honma Y, Iwasa S, Okita N, Takashima A, Kato K, Nagai Y, Taniguchi H, Boku N, Ushijima T, Shimada Y. Value of KRAS, BRAF, and PIK3CA Mutations and Survival Benefit from Systemic Chemotherapy in Colorectal Peritoneal Carcinomatosis. Asian Pac J Cancer Prev, 17:539-543, 2016

49.Sato S, Kitahara A, Koike T, Hashimoto T, Ohashi R, Motoi N, Tsuchida M. Resection of a large ectopic parathyroid adenoma: A case report. Int J Surg Case Rep, 23:8-11, 2016

50.Sato Y, Kinoshita T, Suzuki J, Jimbo K, Asaga S, Hojo T, Yoshida M, Tsuda H. Preoperatively diagnosed ductal carcinoma in situ: risk prediction of invasion and effects on axillary management. Breast Cancer, 23:761-770, 2016

51.Seki Y, Fujiwara Y, Kohno T, Takai E, Sunami K, Goto Y, Horinouchi H, Kanda S, Nokihara H, Watanabe S, Ichikawa H, Yamamoto N, Kuwano K, Ohe Y. Picoliter-Droplet Digital Polymerase Chain Reaction-Based Analysis of Cell-Free Plasma DNA to Assess EGFR Mutations in Lung Adenocarcinoma That Confer Resistance to Tyrosine-Kinase Inhibitors. Oncologist, 21:156-164, 2016

52.Sekiguchi M, Oda I, Taniguchi H, Suzuki H, Morita S, Fukagawa T, Sekine S, Kushima R, Katai H. Risk stratification and predictive risk-scoring model for lymph node metastasis in early gastric cancer. J Gastroenterol, 51:961-970, 2016

53.Sekine S, Yamashita S, Tanabe T, Hashimoto T, Yoshida H, Taniguchi H, Kojima M, Shinmura K, Saito Y, Hiraoka N, Ushijima T, Ochiai A. Frequent PTPRK-RSPO3 fusions and RNF43 mutations in colorectal traditional serrated adenoma. J Pathol, 239:133-138, 2016

54.Sekine S, Yoshida H, Jansen M, Kushima R. The Japanese Viewpoint on the Histopathology of Early Gastric Cancer. Adv Exp Med Biol, 908:331-346, 2016

55.Setsu N, Miyake M, Wakai S, Nakatani F, Kobayashi E, Chuman H, Hiraoka N, Kawai A, Yoshida A. Primary Retroperitoneal Myxoid Liposarcomas. Am J Surg Pathol, 40:1286-1290, 2016

56.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

57.Shigenobu T, Motoi N, Asamura H, Watanabe S, Hiraoka N, Yoshida A. Giant lamellar bodies associated with adenocarcinoma of the lung. Histopathology, 69:1090-1092, 2016

58.Shiina S, Ohno M, Ohka F, Kuramitsu S, Yamamichi A, Kato A, Motomura K, Tanahashi K, Yamamoto T, Watanabe R, Ito I, Senga T, Hamaguchi M, Wakabayashi T, Kaneko MK, Kato Y, Chandramohan V, Bigner DD, Natsume A. CAR T Cells Targeting Podoplanin Reduce Orthotopic Glioblastomas in Mouse Brains. Cancer Immunol Res, 4:259-268, 2016

59.Shiino S, Kinoshita T, Yoshida M, Jimbo K, Asaga S, Takayama S, Tsuda H. Prognostic Impact of Discordance in Hormone Receptor Status Between Primary and Recurrent Sites in Patients With Recurrent Breast Cancer. Clin Breast Cancer, 16:e133-140, 2016

60.Shiraishi K, Okada Y, Takahashi A, Kamatani Y, Momozawa Y, Ashikawa K, Kunitoh H, Matsumoto S, Takano A, Shimizu K, Goto A, Tsuta K, Watanabe S, Ohe Y, Watanabe Y, Goto Y, Nokihara H, Furuta K, Yoshida A, Goto K, Hishida T, Tsuboi M, Tsuchihara K, Miyagi Y, Nakayama H, Yokose T, Tanaka K, Nagashima T, Ohtaki Y, Maeda D, Imai K, Minamiya Y, Sakamoto H, Saito A, Shimada Y, Sunami K, Saito M, Inazawa J, Nakamura Y, Yoshida T, Yokota J, Matsuda F, Matsuo K, Daigo Y, Kubo M, Kohno T. Association of variations in HLA class II and other loci with susceptibility to EGFR-mutated lung adenocarcinoma. Nat Commun, 7:12451, 2016

61.Sugano K, Nakajima T, Sekine S, Taniguchi H, Saito S, Takahashi M, Ushiama M, Sakamoto H, Yoshida T. Germline PMS2 mutation screened by mismatch repair protein immunohistochemistry of colorectal cancer in Japan. Cancer Sci, 107:1677-1686, 2016

62.Sunami K, Furuta K, Tsuta K, Sasada S, Izumo T, Nakaoku T, Shimada Y, Saito M, Nokihara H, Watanabe S, Ohe Y, Kohno T. Multiplex Diagnosis of Oncogenic Fusion and MET Exon Skipping by Molecular Counting Using Formalin-Fixed Paraffin Embedded Lung Adenocarcinoma Tissues. J Thorac Oncol, 11:203-212, 2016

63.Tabe Y, Hatanaka Y, Nakashiro M, Sekihara K, Yamamoto S, Matsushita H, Kazuno S, Fujimura T, Ikegami T, Nakanaga K, Matsumoto H, Ueno T, Aoki J, Yokomizo T, Konopleva M, Andreeff M, Miida T, Iwabuchi K, Sasai K. Integrative genomic and proteomic analyses identifies glycerol-3-phosphate acyltransferase as a target of low-dose ionizing radiation in EBV infected-B cells. Int J Radiat Biol, 92:24-34, 2016

64.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

65.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

66.Takagi Y, Hosomi Y, Nagamata M, Watanabe K, Takahashi S, Nakahara Y, Yomota M, Sunami K, Okuma Y, Shimokawa T, Okamura T. Phase II study of oral vitamin B12 supplementation as an alternative to intramuscular injection for patients with non-small cell lung cancer undergoing pemetrexed therapy. Cancer Chemother Pharmacol, 77:559-564, 2016

67.Takahashi H, Watanabe T, Kinoshita A, Yuza Y, Moritake H, Terui K, Iwamoto S, Nakayama H, Shimada A, Kudo K, Taki T, Yabe M, Matsushita H, Yamashita Y, Koike K, Ogawa A, Kosaka Y, Tomizawa D, Taga T, Saito AM, Horibe K, Nakahata T, Miyachi H, Tawa A, Adachi S. High event-free survival rate with minimum-dose-anthracycline treatment in childhood acute promyelocytic leukaemia: a nationwide prospective study by the Japanese Paediatric Leukaemia/Lymphoma Study Group. Br J Haematol, 174:437-443, 2016

68.Takahashi K, Yoshida H, Watanabe R, Ishikawa M, Ikeda SI, Kato T. Metastasis of extra-ampullary duodenal adenocarcinoma to the uterine cervix. Malays J Pathol, 38:45-48, 2016

69.Takahashi N, Iwasa S, Taniguchi H, Sasaki Y, Shoji H, Honma Y, Takashima A, Okita N, Kato K, Hamaguchi T, Shimada Y, Yamada Y. Prognostic role of ERBB2, MET and VEGFA expression in metastatic colorectal cancer patients treated with anti-EGFR antibodies. Br J Cancer, 114:1003-1011, 2016

70.Tamura N, Tsuda H, Yoshida M, Hojo T, Akashi-Tanaka S, Kinoshita T, Sugihara K. Clinicopathological predictive factors for ipsilateral and contralateral events following initial surgery to treat ductal carcinoma in situ. Breast Cancer, 23:510-518, 2016

71.Tanabe Y, Ichikawa H, Kohno T, Yoshida H, Kubo T, Kato M, Iwasa S, Ochiai A, Yamamoto N, Fujiwara Y, Tamura K. Comprehensive screening of target molecules by next-generation sequencing in patients with malignant solid tumors: guiding entry into phase I clinical trials. Mol Cancer, 15:73, 2016

72.Tanaka M, Kishi Y, Esaki M, Nara S, Miyake M, Hiraoka N, Nagino M, Shimada K. Feasibility of Routine Application of Gadoxetic Acid-Enhanced MRI in Combination with Diffusion-Weighted MRI for the Preoperative Evaluation of Colorectal Liver Metastases. Ann Surg Oncol, 23:3991-3998, 2016

73.Tanaka M, Nakajima T, Sugano K, Yoshida T, Taniguchi H, Kanemitsu Y, Nagino M, Sekine S. Mismatch repair deficiency in Lynch syndrome-associated colorectal adenomas is more prevalent in older patients. Histopathology, 69:322-328, 2016

74.Tsuruki ES, Saito Y, Abe S, Takamaru H, Yamada M, Sakamoto T, Nakajima T, Matsuda T, Sekine S, Taniguchi H. Evaluating the efficacy and safety of a novel endoscopic fluorescence imaging modality using oral 5-aminolevulinic acid for colorectal tumors. Endosc Int Open, 4:E30-35, 2016

75.Ueda R, Maruyama D, Nomoto J, Maeshima AM, Fukuhara S, Kitahara H, Miyamoto K, Munakata W, Suzuki T, Taniguchi H, Kobayashi Y, Tobinai K. FUS-ERG gene fusion in isolated myeloid sarcoma showing uncommon clinical features. Oxf Med Case Reports, 2016:4-8, 2016

76.Watanabe Y, Kusumoto M, Yoshida A, Shiraishi K, Suzuki K, Watanabe S, Tsuta K. Cavity Wall Thickness in Solitary Cavitary Lung Adenocarcinomas Is a Prognostic Indicator. Ann Thorac Surg, 102:1863-1871, 2016

77.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

78.Yamamoto H, Lu J, Oba S, Kawamata T, Yoshimi A, Kurosaki N, Yokoyama K, Matsushita H, Kurokawa M, Tojo A, Ando K, Morishita K, Katagiri K, Kotani A. miR-133 regulates Evi1 expression in AML cells as a potential therapeutic target. Sci Rep, 6:19204, 2016

79.Yoshida A, Goto K, Kodaira M, Kobayashi E, Kawamoto H, Mori T, Yoshimoto S, Endo O, Kodama N, Kushima R, Hiraoka N, Motoi T, Kawai A. CIC-rearranged Sarcomas: A Study of 20 Cases and Comparisons With Ewing Sarcomas. Am J Surg Pathol, 40:313-323, 2016

80.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

81.Yuda S, Maruyama D, Maeshima AM, Makita S, Kitahara H, Miyamoto K, Fukuhara S, Munakata W, Suzuki T, Kobayashi Y, Tajima K, Taniguchi H, Tobinai K. Influence of the watch and wait strategy on clinical outcomes of patients with follicular lymphoma in the rituximab era. Ann Hematol, 95:2017-2022, 2016

Book

1.Tsuda, Hitoshi (et al.). Histopathological Evaluation of the Therapeutic Effect of RFA for Early Breast Cancer. In: Kinoshita, Takayuki (eds), Non-surgical Ablation Therapy for Early-stage Breast Cancer, 東京, Springer Japan, pp 77-88, 2016

2.Varella-Garcia M, Yoshida A. Chapter 7. ROS1 Testing with FISH. In: Ming Sound Tsao, Fred R. Hirsch, Yasushi Yatabe (eds), IASLC Atlas of ALK and ROS1 Testing in Lung Cancer 2nd ed., United States of America, Editorial Rx Press, pp 53-61, 2016

3.Yoshida A, Bubendorf L, Varella-Garcia M. Chapter 6. ALK Testing with FISH. In: Ming Sound Tsao, Fred R. Hirsch, Yasushi Yatabe (eds), IASLC Atlas of ALK and ROS1 Testing in Lung Cancer 2nd ed., United States of America, Editorial Rx Press, pp 41-52, 2016