Department of Pathology, The University of Tokyo
Biennial Report 2001
Department of Human Pathology and Diagnostic Pathology
ProfessorMasashi Fukayama, M.D., D.M.Sc.
Associate ProfessorToshiro Niki, M.D., D.M.Sc.
(Tsuyoshi Tange, M.D., D.M.Sc.)
LecturerJa-Mun Chong, M.D., Ph.D.*
AssociateTakeshi Kashima, M.D., Ph.D.
Hiroshi Uozaki, M.D., D.M.Sc.
(Kengo Takeuchi, M.D., D.M.Sc.)
(Noriko Motoi, M.D., D.M.Sc.)
Akiteru Goto, M.D., D.M.Sc.
Tateru Ishida, M.D., D.M.Sc.


The staffs consist of a professor, an associate professor, a lecturer, and 3 associates. Dr. Tsuyoshi Tange moved to the branch hospital as an associate professor on July 1, 2000, and Dr. Toshiro Niki, who was a chief investigator of National Cancer Center, is now an associate professor of our department. Dr. Takashi Kashima (*) is studying in King's College London, Guy's Hospital. Dr. Kengo Takeuchi moved to the Tokyo University Hospital, and Dr. Noriko Motoi to the Toranomon Hospital. Dr. Akiteru Goto and Dr. Tateru Ishida are in the position from April 2001. Eight postgraduate students and one visiting researcher are now studying in the department. We are investigating the human diseases on the basis of the morphology, and also contribute to the clinical activities, autopsy and surgical pathology, of the University Hospital.

Teaching Activities

Education for the undergraduate students consists of the lectures on general pathology for the 1st grade-students, and the lectures and exercise course of systemic pathology for the 2nd grade-students, and the bed-side learning (BSL) course of autopsy and surgical pathology and clinico-pathologic conferences (CPC) for 3rd -4th grade students. The education is undertaken in collaboration with the staffs of the Department of Molecular Pathology and the Department of Pathology of the University Hospital. A free-quarter course is provided for applicants of the 2nd grade students.
Education for postgraduate students is basically through practice and research of human pathology.

Clinical Activities

Practice of autopsy and surgical pathology of the University Hospital is supported by our staffs. CPCs are held every month in the hospital, for the autopsy cases, and various diseases, such as lymphoma, respiratory diseases, upper gastrointestinal tract diseases, liver tumors, bone- and soft tissue tumors, and gynecological tumors.

Research Activities

Human pathology has two aspects: discovery of a new entity of human diseases and museum for various forms of human disorders. Our research projects for the first aspect are to investigate the mechanism of the following diseases:
1. Epstein-Barr virus associated neoplasms, such as gastric carcinomas, pyothorax-associated lymphoma, Hodgkin's disease and AIDS lymphomas.
2. Human herpes virus 8 associated neoplasms, such as Kaposi sarcoma and multicentric Castleman's disease.
3. Lung carcinomas with or without pulmonary fibrosis, and pulmonary metastasis of carcinomas, e.g. osteosarcoma.
The project for the second aspect is now beginning for lymphomas and arteritis. Since we have stocks of paraffin blocks of more than 28000 autopsy cases during these 100 years, a new molecular approach will clarify changes of these diseases in the 20th century of Japan.


  1. Hishima T, Fukayama M, Hayashi Y, Fujii T, Ooba T, Funata N, Koike M: CD70 in thymic carcinoma. Am J Surg Pathol 25:742-746, 2000.
  2. Kitagawa N, Goto M, Kurozumi K, Maruo S, Fukayama M, Naoe T, Yasukawa M, Hino K, Suzuki T, Todo S, Takada K: Epstein-Barr virus-encoded poly (A)-RNA supports Burkitt's lymphoma growth through interleukin-10 induction. EMBO J 19:6742-6750, 2000.
  3. Maki M, Saitoh K, Kaneko Y, Fukayama M, Morohoshi T: Expression of cytokeratin 1, 5, 14, 19 and transforming factors-b1, b 2, b 3 in osteofibrous dysplasia and adamantinoma: a possible association of transforming growth factor- b with basal cell phenotype promotion. Pathol Int 50:801-807, 2000.
  4. Ozawa A, Konishi F, Fukayama M, Kanazawa K: Apoptosis and its regulation in flat-type early colorectal carcinoma. Comparison with that in polypoid-type early colorectal carcinoma. Dis Colon Rectum 43:S23-S28, 2000.
  5. Sasaki J, Ishikawa K, Kobayashi K, Kondo-Iida E, Fukayama M, Mizusawa H, Takashima S, Sakakihara Y, Nakamura Y, Toda T: Neuronal expression of the fukutin gene. Hum Mol Gen 20:3083-3090, 2000.
  6. Kuriki K, Kamiakito T, Yoshida H, Saito K, Fukayama M, Tanaka A: integration of proviral sequences, but not at the common integration sites of the FGF8 locus, in an androgen-dependent mouse mammary Shionogi carcinoma. Cell Mol Biol 46:1147-1156, 2000.
  7. Urasaki K, Kuriki K, Namerikawa M, Satoh S, Ikeguchi K, Fukayama M, Saito K, Nakano I: An autopsy case of Alzheimer's disease with a progressive supranuclear palsy overlap. Neuropathol 20:233-238, 2000.
  8. Chong JM, Koshiishi N, Kurihara K, Kubono S, Kawai T, Fukayama M: Aspiration and imprint cytopathology of thyroid carcinoma associated with familial adenomatous polyposis. Diagn Cytopathol 23:101-105, 2000.
  9. Kurihara K, Shimizu S, Chong JM, Hishima T, Funata N, Kashiwagi H, Nagai H, Miyaki M, Fukayama M: Nuclear localization of immunorective b -catenin is specific to familial adenomatous polyposis in papillary thyroid carcinoma. Jpn J Cancer Res 91:1100-1102, 2000.
  10. Fukasawa T, Chong JM, Sakurai S, Koshiishi N, Ikeno R, Tanaka A, Matsumoto Y, Hayashi Y, Koike M, Fukayama M: Allelic loss of 14q, and 22q, NF2 mutation, and genetic instability occur independently of c-kit mutation in gastrointestinal stromal tumor. Jpn J Cancer Res 91:1241-1249, 2000.
  11. Seo S, Kami M, Honda H, Kashima T, Matsumura T, Moriya A, Machida U, Kanda Y, Chiba S, Hirai H: Extramedullary relapse in the so-called sanctuary sites for chemotherapy after donor lymphocyte infusion. Bone Marrow Trasnplant 25:226-227, 2000.
  12. Kami M, Tanaka Y, Masumoto T, Kanda Y, Kashima T, Matsumura T, Machida U, Saito T, Ogawa S, Ohtomo K, Hirai H: Computed tomographic scan of the chest, latex agglutination test and plasma (1, 3)-beta-D-glucan assay in early diagnosis of invasive pulmonary aspergillosis: A prospective study of 215 patients. Haematlogica, 85:745-752, 2000.
  13. Uozaki H, Ishida T, Kakiuchi C, Horiuchi H, Gotoh T, Iijima T, Imamura T, Machinami R: Expression of heat shock proteins in osteosarcoma and its relationship to prognosis. Pathol Res Pract, 196:665-673, 2000.
  14. Machida U, Kami M, Uozaki H, Makimura K, Yamaguchi H, Hirai H: Subacute spinal cord infarction due to zygomycotic thrombosis in a patient with myelodysplastic syndrome. Haematologica, 85:1004-1006, 2000.
  15. Yamauchi T, Yamauchi N, Ueki K, Sugiyama T, Waki H, Miki H, Tobe K, Matsuda S, Tsushima T, Yamamoto T, Fujita T, Taketani Y, Fukayama M, Kimura S, Yazaki Y, Nagai R, Kadowaki T: Constitutive tyrosine phosphorylation of ErbB-2 via Jak2 by autocrine sevretion of prolactin in human breast cancer. J Biol Chem 275:33937-33944, 2000.
  16. Inoue K, Numaga J, Kaji Y, Toda J, Kato S, Sakurai M, Ikeda M, Motoi N, Murakami T, Fujino Y; Bilateral choroidal metastases secondary to uterocervical carcinoma of the squamous cell type. Am J Ophthalmol. 130:682-684, 2000.
  17. Motoi N, Sakamoto A, Yamochi T, Horiuchi H, Motoi T, Machinami R. Role of ras mutation in the progression of thyroid carcinoma of follicular epithelial origin. Pathol Res Pract. 196:1-7, 2000.
  18. Imai Y, Kurokawa M, Izutsu K, Hangaishi A, Takeuchi K, Maki K, Ogawa S, Chiba S, Mitani K, Hirai H: Mutations of the AML1 gene in myelodysplastic syndrome and their functional implications in leukemogenesis. Blood 96:3154-3160, 2000.
  19. Suzuki R, Kagami Y, Takeuchi K, Kami M, Okamoto M, Ichinohasama R,Mori N, Kojima M, Yoshino T, Yamabe H, Shiota M, Mori S, Ogura M, Hamajima N, Seto M, Suchi T, Morishima Y, Nakamura S: Prognostic significance of CD56 expression for ALK-positive and ALK-negative anaplastic large-cell lymphoma of T/null cell phenotype. Blood 96:2993-3000, 2000.
  20. Iwata H, Kami M, Kishi Y, Oki Y, Tanaka Y, Takeuchi K, Yamazaki I, Suzuki R, Morinaga S, Mutou Y: Limitations of the diagnostic criteria for minimally differentiated acute myeloid leukemia (AML-MO). Leukemia 14:2013-2014, 2000.
  21. WHO classification of malignant lymphomas in Japan: Incidence of recently recognized entities, Cooperative study of lymphoma study group of Japanese pathologists, Pathol Int, 50: 696-702, 2000.
  22. Kitazawa J, Ito E, Arai K, Yokoyama M, Fukayama M, Imashuku S. Secondary acute myelocytic leukemia after successful chemotherapy with etoposide for Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis. Med Pediatr Oncol, 37:153-154, 2001.
  23. Sakurai S, Hishima T, Takazawa Y, Sano T, Nakajima T, Saito K, Morinaga S, Fukayama M. Gastrointestinal stromal tumors and KIT-positive mesenchymal cells in the omentum. Pathol Int, 51:524-531, 2001.
  24. Nagashima T, Muroi K, Kunitama M, Izumi T, Ohtsuki T, Komatsu N, Fukayama M, Ozawa K. Colon cancer with meningeal carcinomatosis and myelodysplastic syndrome in a patient who underwent intensive chemotherapy for acute myelogenous leukemia: a case report. Jpn J Clin Oncol, 31:221-225, 2001.
  25. Fukayama M, Chong JM, Uozaki H. Pathology and molecular pathology of Epstein-Barr virus-associated gastric carcinoma. Curr Top Microbiol Immunol, 258:91-102, 2001.
  26. Tanaka A, Hasegawa Y, Hakamata Y, Kamiakito T, Kuriki K, Yoshida H, Fukayama M. Purification of activins from androgen-independent Shionogi carcinoma cells demonstrates enhanced expression of activin betaB-subunit under androgen-depleted cell conditions in vitro and in vivo. J Cell Physiol. 188(2):194-200, 2001.
  27. Takeuchi K, Morishita Y, Fukayama M, Mori S. Marked decrease in the Epstein-Barr virus positivity rate in nodular sclerosis subtype Hodgkin's disease in Tokyo: trend between 1955 and 1999. Br J Haematol, 113:429-431, 2001.
  28. Kobayashi M, Kinouchi T, Hakamata Y, Kamiakito T, Kuriki K, Suzuki K, Tokue A, Fukayama M, Tanaka A. Isolation of an androgen-inducible novel lipocalin gene, Arg1, from androgen-dependent mouse mammary Shionogi carcinoma cells. J Steroid Biochem Mol Biol, 77:109-115, 2001.
  29. Sakurai S, Oguni S, Hironaka M, Fukayama M, Morinaga S, Saito K. Mutations in c-kit gene exons 9 and 13 in gastrointestinal stromal tumors among Japanese. Jpn J Cancer Res. 92:494-498, 2001.
  30. Hironaka M, Fukayama M, Takayashiki N, Saito K, Sohara Y, Funata N. Pulmonary gangliocytic paraganglioma: case report and comparative immunohistochemical study of related neuroendocrine neoplasms. Am J Surg Pathol, 26:688-693, 2001.
  31. Fukayama M, Yoshino T, Nakamura S. Pathology in Germany and Finland: a brief report of the delegates of the Japanese Society of Pathology. Pathol Int, 51:221-225, 2001.
  32. Murakami T, Fukasawa T, Fukayama M, Usui K, Ohtsuki M, Nakagawa H. Gene expression profile in a case of primary cutaneous CD30-negative large T-cell lymphoma with a blastic phenotype. Clin Exp Dermatol. 26:201-204. 2001.
  33. Tanaka A, Kamiakito T, Hakamata Y, Fujii A, Kuriki K, Fukayama M. Extensive neuronal localization and neurotrophic function of fibroblast growth factor 8 in the nervous system. Brain Res. 7; 912:105-115, 2001.
  34. Yamauchi T, Waki H, Kamon J, Murakami K, Motojima K, Komeda K, Miki H, Kubota N, Terauchi Y, Tsuchida A, Tsuboyama-Kasaoka N, Yamauchi N, Ide T, Hori W, Kato S, Fukayama M, Akanuma Y, Ezaki O, Itai A, Nagai R, Kimura S, Tobe K, Kagechika H, Shudo K, Kadowaki T. Inhibition of RXR and PPARgamma ameliorates diet-induced obesity and type 2 diabetes. J Clin Invest, 108:1001-1013, 2001.
  35. Kobayashi Y, Nakata M, Maekawa M, Takahashi M, Fujii H, Matsuno Y, Fujishiro M, Ono H, Saito D, Takenaka T, Hirase N, Nishimura J, Akioka T, Enomoto K, Mikuni C, Hishima T, Fukayama M, Sugano K, Hosoda F, Ohki M, Tobinai K: Detection of t(I 1; 18) in MALT-type lymphoma with dual-color fluorescence in situ hybridization and reverse transcriptase-polymerase chain reaction analysis. Diagn Mol Pathol, 10:207-213, 2001.
  36. Terasaki H, Niki T, Hasegawa T, Yamada T, Suzuki, Kusumoto M, Fujimoto K, Hayabuchi N, Matsuno Y, Shimoda T. Primary synovial sarcoma of the lung: a case report confirmed by molecular detection of SYT-SSX fusion gene transcript. Jpn J Clin Oncol 31: 212-6, 2001.
  37. Masaki T, Goto A, Sugiyama M, Matsuoka H, Abe N, Sakamoto A, Atomi Y: Possible Contribution of CD44 variant 6 and Nuclear Beta-Catenin Expression to the Formation of Budding Tumor Cells in Patients with T1 Colorectal Carcinoma. Cancer, 92:2539-2546, 2001.
  38. Goto A, Sakamoto A, Machinami R: An Immunohistochemical analysis of cyclinD1, p53, and p21waf1/cip1 proteins in tumors originating from the follicular epithelium of the thyroid gland. Pathol Res Pract, 197:217-222, 2001.
  39. Masaki T, Matsuoka H, Sugiyama M, Abe N, Goto A, Sakamoto A, Atomi Y: Matrilysin (MMP-7) as a significant determinant of malignant potential of early invasive colorectal carcinomas. Br J Cancer, 84:1317-1321, 2001.
  40. Tabata M. Kitagawa T. Saito T. Uozaki H. Oshiro H. Miyata T. Shigematsu H: Extracranial carotid aneurysm in Takayasu's arteritis. J Vas Surg, 34:739-742, 2001
  41. Miyairi T, Kotsuka Y, Morota T, Kubota H, Shibata K, Ikeda Y, Kitamura T, Kashima T, Takamoto S: Paraplegia after open surgery using endovascular stent graft for aortic arch aneurysm. J Thorac Cardiovas Surg, 122:1240-1243, 2001
  42. Hippo Y, Taniguchi H, Tsutsumi S, Machida N, Chong JM, Fukayama M, Kodama T, Aburatani H. Global gene expression analysis of gastric cancer by oligonucleotide microarrays. Cancer Res, 62:233-240, 2002.
  43. Niki T, Kohno T, Iba S, Moriya Y, Takahashi Y, Saito M, Maeshima A, YamadaT, Matsuno Y, Fukayama M, Yokota J, Hirohashi S. Frequent Co-Localization of Cox-2 and Laminin-5 gamma2 Chain at the Invasive Front of Early-Stage Lung Adenocarcinomas. Am J Pathol, 160:1129-1141, 2002.

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