Biennial Report 2003

Department of Human Pathology and Diagnostic Pathology
Professor	Masashi Fukayama, M.D., Ph.D.
Associate Professor	Toshiro Niki, M.D., Ph.D.
	Ken-ichi Ohashi, M.D., Ph.D.
Lecturer	Ja-Mun Chong, M.D., Ph.D.*
Associate	Takeshi Kashima, M.D., Ph.D.
	Akiteru Goto, M.D., Ph.D.
	Junji Shibahara, M.D., Ph.D.
	Tetsuo Ushiku, M.D., Ph.D.
Division of Diagnostic Pathology, University Hospital
Lecturer	Hisako Endo, M.D., Ph.D.
	Toru Motoi, M.D., Ph.D.
	Hiroshi Uozaki, M.D., Ph.D.
Associate	Yutaka Takazawa, M.D., Ph.D.
	Yasunori Ohta, M.D., Ph.D.
	(Naoko Yamauchi, M.D., Ph.D.)

Organization

Department of Human Pathology and Division of Diagnostic Pathology of University Hospital have been merged to function as a unit, like other departments of clinical medicine. This union declares the responsibility of our departments for pathological practice, autopsy and surgical pathology, of the University Hospital, and education and research of human pathology. It is also expected to facilitate the translational research in the hospital. The staffs consist of a professor, two associate professor, three lecturers and six associates. Dr. Ken-ichi Ohashi, who was a chief pathologist of Tokyo Metropolitan Komagome Hospital, is now an associate professor of our department. Dr. Ja-Mun Chong (*) is studying abroad in Department of Virology, Johns Hopkins University. Dr. Naoko Yamauchi resigned, but still continues to work as a visiting scientist. Dr. Tetsuo Ushiku and Dr. Yasunori Ohta will be in the position from April 2004. Sixteen postgraduate students and four visiting researchers are now studying in the department.

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. Clinical clerkship and bed-side learning (BSL) course of autopsy and surgical pathology are for 3rd and 4th grade students, respectively. The education for general pathology is undertaken in collaboration with the staffs of the Department of Molecular Pathology. A short course for the research activities is provided for applicants of the 2nd grade students. Education for postgraduate students is basically through practice and research of human pathology.

Clinical Activities

Activities of pathology practice, autopsy and surgical pathology of the University Hospital, is described in the section of Division of Pathology, University Hospital. CPCs are held every month in the hospital, for the autopsy cases, and for 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. Our research projects are to investigate the mechanism of the following diseases:

Epstein-Barr virus associated neoplasms, such as gastric carcinomas, pyothorax-associated lymphoma, Hodgkin's disease and AIDS lymphomas. .
Lung carcinomas with or without pulmonary fibrosis, and pulmonary metastasis of carcinomas, e.g. osteosarcoma. We are also developing the tumor specific antibodies in collaboration with Genome Science Division, Research Center for Advanced Science and Technology, the University of Tokyo. Based on the DNA array data of various human neoplasms, monoclonal antibodies are now generated for the candidate gene products. To facilitate the screening process of immunohistochemistry, we are now developing the tissue array for neoplastic and non-neoplastic tissues.

References

2002

Chiba S, Saito A, Ogawa S, Takeuchi K, Kumano K, Seo S, Suzuki T, Tanaka Y, Saito T, Izutsu K, Yuji K, Masuda S, Futami S, Nishida M, Suzuki G, Gale RP, Fukayama M, Maekawa K, Hirai H. Transplantation for accidental acute high-dose total body neutron- and gamma-radiation exposure. Bone Marrow Transplant, 29:935-939, 2002
Chong J-M, Sakuma K, Sudo M, Osawa T, Ohara E, Uozaki H, Shibahara J, Kuroiwa K, Tominaga S, Hippo Y, Aburatani H, Funata N, Fukayama M. Interleukin-1b expression in human gastric carcinoma with Epstein-Barr virus infection. J Virol, 76: 6825-6831, 2002
Enomoto A, Wempe MF, Tsuchida H, Shin HJ, Cha SH, Anzai N, Goto A, Sakamoto A, Niwa T, Kanai Y, Anders MW, Endou H. Molecular identification of a novel carnitine transporter specific to human testis. Insights into the mechanism of carnitine recognition. J Biol Chem. 277:36262-71.2002
Goto T, Kojima T, Iijima T, Yokokura S, Motoi T, Kawano H, Yamamoto A, Matsuda K. Intraosseous lipoma: a clinical study of 12 patients. J Orthop Sci, 7:274-280, 2002.
Ishiguro N, Baba T, Ishida T, Takeuchi K, Osaki M, Araki N, Okada E, Takahashi S, Saito M, Watanabe M, Nakada C, Tsukamoto Y, Sato K, Ito K, Fukayama M, Mori S, Ito H, Moriyama M. Carp, a cardiac ankyrin-repeated protein, and its new homologue, Arpp, are differentially expressed in heart, skeletal muscle, and rhabdomyosarcomas. Am J Pathol, 160:1767-1778, 2002
Kakiuchi C, Ishida T, Sato H, Katano H, Ishiko T, Mukai H, Kogi M, Kasuga N, Takeuchi K, Yamane K, Fukayama M, Mori S. Secretion of interleukin-6 and vascular endothelial growth factor by spindle cell sarcoma complicating Castleman's disease (so-called 'vascular neoplasia'). J Pathol, 197:264-271, 2002
Kami M, Machida U, Okuzumi K, Matsumura T, MoriSi S, Hori A, Kashima T, Kanda Y, Takaue Y, Sakamaki H, Hirai H, Yoneyama A, Mutou Y. Effect of fluconazole prophylaxis on fungal blood cultures: an autopsy-based study involving 720 patients with haematological malignancy. Br J Haematol, 117: 40-46, 2002.
Kami M, Kishi Y, Hamaki T, Kawabata M, Kashima T, Masumoto T, Oki Y, Tanaka Y, Sawada S, Machida U, Ohtomo K, Kanda Y, Hirai H, Mutou Y. The value of the chest computed tomography halo sign in the diagnosis of invasive pulmonary aspergillosis. An autopsy-based retrospective study of 48 patients. Mycoses 45: 287-294, 2002.
Kanno T, Endo H, Takeuchi K, Morishita Y, Fukayama M, Mori S. High expression of methionine aminopeptidase type 2 in germinal center B cells and their neoplastic counterparts. Lab Invest, 82:893-901, 2002
Maeshima AM, Niki T, Maeshima A, Yamada T, Kondo H, Matsuno Y. Modified scar grade: a prognostic indicator in small peripheral lung adenocarcinoma. Cancer, 95:2546-2554, 2002
Murakawa T, Nakajima J, Sato H, Tanaka M, Takamoto S, Fukayama M. Thymoma associated with pure red-cell aplasia: Clinical features and prognosis. Asian Cardiovasc Thorac Ann, 10:150-154, 2002
Nagamine N, Ido K, Saihuku K, Higashizawa T, Ono K, Hirasawa T, Sugano K, Chong J-M Photodynamic effects on rabbit auricular veins after photosensitization with porfimer sodium: implications of the results with respect to the treatment of esophageal varices with photodynamic therapy. Gastrointestinal Endoscopy 55: 420-424. 2002
Nakajima J, Takamoto S, Tanaka M, Takeuchi E, Murakawa T, Kitagawa H, Fukayama M. Parathyroid adenoma manifested by mediastinal hemorrhage: report of a case. Surg Today, 32:809-811, 2002
Nishioka M, Kohno T, Tani M, Yanaihara N, Tomizawa Y, Otsuka A, Sasaki S, Kobayashi K, Niki T, Maeshima A, Sekido Y, Minna JD, Sone S, Yokota J. MYO18B, a candidate tumor suppressor gene at chromosome 22q12.1, deleted, mutated, and methylated in human lung cancer. Proc Natl Acad Sci U S A, 99:12269-12274, 2002
Osawa T, Chong J-M, Sudo M, Sakuma K, Uozaki H, Shibahara J, Nagai H, Funata N, Fukayama M. Reduced expression and promotor mehtylation of p16 gene in Epstein-Barr virus-associated gastric carcinoma. Jpn J Cancer Res, 93:1195-1200, 2002
Rombouts K, Niki T, Greenwel P, Vandermonde A, Wielant A, Hellemans K, De Bleser P, Yoshida M, Schuppan D, Rojkind M, Geerts A. Trichostatin A, a histone deacetylase inhibitor, suppresses collagen synthesis and prevents TGF-beta(1)-induced fibrogenesis in skin fibroblasts. Exp Cell Res, 78:184-197, 2002.
Takayasu H, Motoi T, Kanamori Y, Kitano Y, Nakanishi H, Tange T, Nakagawara A, Hashizume K. Two case reports of childhood liver cell adenomas harboring beta-catenin abnormalities. Hum Pathol, 33:852-855, 2002.
Takei H, Asamura H, Maeshima A, Suzuki K, Kondo H, Niki T, Yamada T, Tsuchiya R, Matsuno Y. Large cell neuroendocrine carcinoma of the lung: A clinicopathologic study of eighty-seven cases. J Thorac Cardiovasc Surg, 124: 285-292, 2002
Tomizawa Y, Kohno T, Kondo H, Otsuka A, Nishioka M, Niki T, Yamada T, Maeshima A, Yoshimura K, Saito R, Minna JD, Yokota J. Clinicopathological significance of epigenetic inactivation of RASSF1A at 3p21.3 in stage I lung adenocarcinoma. Clin Cancer Res, 8: 2362-2368, 2002
Ueda E, Kitayama J, Seto Y, Motoi T, Nagawa H. Postoperative complications after local resection of the stomach. Surg Today, 32:305-309, 2002.
Yoshizawa K, Nagai H, Sakurai S, Hironaka M, Morinaga S, Saitoh K, Fukayama M. Clonality and K-ras mutation analyses of epithelia in intraductal papillary mucinous tumor and mucinous cystic tumor of the pancreas. Virchows Arch. 441:437-443, 2002

2003

Asaba K, Tojo A, Onozato ML, Mimura N, Kido M, Goto A, Endo H, Fujita T. Fibrillary glomerulonephritis associated with essential thrombocytosis. Clin Exp Nephrol. 7:296-300, 2003.
Chong J-M, Sakuma K, Sudo M, Ushiku T, Uozaki H, Shibahara J, Nagai H, Funata N, Taniguchi H, Aburatani H, Fukayama M. Global and non-random CpG-island methylation in gastric carcinoma associated with Epstein-Barr virus. Cancer Sci. 94:76-80, 2003
Fujiwara S, Nakamura I, Goto T, Motoi T, Yokokura S, Nakamura K. Intracortical chondromyxoid fibroma of humerus. Skeletal Radiol. 32(:156-60, 2003.
Goto T, Motoi T, Komiya K, Motoi N, Okuma T, Okazaki H, Takatori Y, Tange T, Nakamura K. Chondrosarcoma of the hand secondary to multiple enchondromatosis; report of two cases. Arch Orthop Trauma Surg. 123:42-7, 2003.
Hoshimoto K, Yamauchi N, Takazawa Y, Onda T, Taketani Y, Fukayama M. CD44 variant 6 in endometrioid carcinoma of the uterus: its expression in the adenocarcinoma component is an independent prognostic marker. Pathol Res Pract. 199:71-7, 2003.
Kanamori Y, Hashizume K, Kitano Y, Sugiyama M, Motoi T, Tange T. Congenital extrahepatic portocaval shunt (Abernethy type 2), huge liver mass, and patent ductus arteriosus--a case report of its rare clinical presentation in a young girl.J Pediatr Surg. 38:E15, 2003.
Kano M, Nishimura K, Ishikawa S, Tsutsumi S, Hirota K, Hirose M, Aburatani H. Expression imbalance map: a new visualization method for detection of mRNA expression imbalance regions. Physiol Genomics, 13:31-46, 2003
Kashima T, Nakamura K, Kawaguchi J, Takanashi M, Ishida T, Aburatani H, Kudo A, Fukayama M, Grigoriadis AE. Overexpression of cadherins suppresses pulmonary metastasis of osteosarcoma in vivo. Int J Cancer. 104:147-54, 2003
Kitagawa H, Goto A, Niki T, Hironaka M, Nakajima J, Fukayama M. Lung adenocarcinoma associated with atypical adenomatous hyperplasia. A clinicopathological study with special reference to smoking and cancer multiplicity. Pathol Int. 53:823-7, 2003.
Kitagawa H, Goto A, Minami M, Nakajima J, Niki T, Fukayama M. Sclerosing hemangioma of the lung with cystic appearance. Jpn J Clin Oncol. 33:360-3, 2003.
Kojima T, Kammori M, Hashimoto M, Ogawa T, Yasuda H, Takazawa Y, Takubo K, Kaminishi M. Diabetic mastopathy in an advanced elderly woman with insulin-dependent type 2 diabetes mellitus. Breast Cancer. 10:374-7, 2003.
Komeno Y, Ogawa S, Ishida T, Takeuchi K, Tsujino S, Kurokawa M, Aoki K, Kanda Y, Chiba S, Motokura T, Fukayama M, Hirai H. Ischemic colitis as a manifestation of thrombotic microangiopathy following bone marrow transplantation. Intern Med. 42:1228-32, 2003.
Kurata A, Machinami R, Schulz A, Fukayama M, Franke FE. Different immunophenotypes in Buerger's disease. Pathol Int. 53:608-15, 2003.
Masaki T, Matsuoka H, Sugiyama M, Abe N, Izumisato Y, Goto A, Sakamoto A, Atomi Y. Laminin-5 gamma 2 chain and matrix metalloproteinase-2 may trigger colorectal carcinoma invasiveness through formation of budding tumor cells. Anticancer Res. 23:4113-9, 2003.
Masaki T, Sugiyama M, Matsuoka H, Abe N, Izumisato Y, Goto A, Sakamoto A, Atomi Y. Clinical utility of grading criteria for submucosal invasion in the prognosis of T1 colorectal carcinomas. J Gastroenterol. 38:37-44.2003
Midorikawa Y, Ishikawa S, Iwanari H, Imamura T, Sakamoto H, Miyazono K, Kodama T, Makuuchi M, Aburatani H. Glypican-3, overexpressed in hepatocellular carcinoma, modulates FGF2 and BMP-7 signaling. Int J Cancer, 103:455-65, 2003
Nakamura K, Nakada C, Takeuchi K, Osaki M, Shomori K, Kato S, Ohama E, Sato K, Fukayama M, Mori S, Ito H, Moriyama M. Altered expression of cardiac ankyrin repeat protein and its homologue, ankyrin repeat protein with PEST and proline-rich region, in atrophic muscles in amyotrophic lateral sclerosis. Pathobiology. 70:197-203, 2002-2003.
Namba A, Nakagawa S, Nakamura N, Takazawa Y, Kugu K, Tsutsumi O, Taketani Y. Ovarian choriocarcinoma arising from partial mole as evidenced by deoxyribonucleic acid microsatellite analysis. Obstet & Gynecol. 102:991-4, 2003.
Ohashi K, Horiguchi S, Moriyama S, Hishima T, Hayashi Y, Momma K, Hanashi T, Izumi Y, Yoshida M, Funata N. Superficial basaloid squamous carcinoma of the esophagus. A clinicopathological and immunohistochemical study of 12 cases. Pathol Res Pract. 199:713-21, 2003.
Ohashi K, Sanaka M, Tu Y, Egawa N, Ohashi K, Funata N, Okuyama Y, Hiruma K, Tanaka Y, Mori S, Akiyama H, Sakamaki H. Clinical features and treatment of hematopoietic stem cell transplantation-associated gastric antral vascular ectasia. Bone Marrow Transplant. 32:417-21, 2003.
Seyama Y, Sakamoto Y, Sano K, Noie T, Motoi T, Takayama T, Makuuchi M. Anatomical segmentectomy of the pancreas head: can this procedure be curatively　applied for intraductal papillary mucinous tumors? Pancreas. 27:270-2, 2003.
Terasaki H, Niki T, Matsuno Y, Yamada T, Maeshima A, Asamura H, Hayabuchi N,　Hirohashi S. Lung adenocarcinoma with mixed bronchioloalveolar and invasive components:　clinicopathological features, subclassification by extent of invasive foci, and immunohistochemical characterization. Am J Surg Pathol. 27:937-51, 2003.
Zhang SC, Miyamoto S, Kamijo T, Hayashi R, Hasebe T, Ishii G, Fukayama M, Ochiai A. Intratumor microvessel density in biopsy specimens predicts local response of hypopharyngeal cancer to radiotherapy. Jpn J Clin Oncol. 33:613-9, 2003.

2004

Liu D, Wada I, Tateno H, Ogino D, Suzuki M, Li L, Lu W, Kojiro M, Fukayama M, Okabe H, Fukumoto M. Allelotypic characteristics of thorotrast-induced intrahepatic cholangiocarcinoma: comparison to liver cancers not associated with thorotrast. Radiat Res. 161:235-43, 2004.
Sudo M, Chong JM, Sakuma K, Ushiku T, Uozaki H, Nagai H, Funata N, MatsumotoY, Fukayama M. Promoter hypermethylation of E-cadherin and its abnormal expression in Epstein-Barr virus-associated gastric carcinoma. Int J Cancer. 109:194-9, 2004.