Name of Division: Surgical Pathology

　　　Under Dr. Morio Koike, Director of Surgical Pathology, the Department offers comprehensive services in surgical pathology, cytology, and autopsy pathology. The scale of these activities currently exceed 6,500 surgical, 7,500 cytology and 95 autopsy examinations.

　

Staff

Education

　　Undergraduate Course

　Department of Surgical Pathology, as well as Dept. of Human Pathology and Dept. of Pathology and Immunology, is responsible for teaching general and systemic pathology for medical students. Our faculty members also participate in other courses such as oncology and "general exercises for clinical diagnosis". Our department also offers exercise programs of surgical and anatomical pathology as "bedside-learning" for 5th and 6th year students.

　　Graduate Course

　We have residency training programs for Surgical and Anatomical Pathology. Research training programs offered for graduate students are listed in the Research section of this page.

　

Research Subjects

　Faculty members of the Department have active research programs in a range of areas of human biology and disease, including Anatomy, Oncology, Immunology and Microbiology.

1. Cancer and basement membrane remodeling:

　In neoplastic tissue, the basement membrane is considered to act as a barrier which hinders the cancer cells from invading the surrounding stroma. In many kind of cancers, disruption of basement membrane and linkage with lymph node metastasis and a poor prognosis have been reported. Two putative processes leading to fragmentation can be hypothesized. One is increased degradation of basement membrane by proteinases, such as collagenase, secreted by the cancer cells themselves or by the surrounding stromal cells. The other possibility is that a reduced capacity of cancer cells to synthesize basement membrane components might exert an influence. We have found that some gastrointestinal and lung cancer cells can not form a basement membrane and this is correlated with reduced expression of laminin a3 and a5 chains, major component of basement membrane. Now we are examining the mechanism of cancer cell invasion in the aspect of interaction between cancer cells and mesenchymal cells and its modulation by basement membrane.

2. Molecular pathology of the esophageal cancer.

　Squamous cell carcinomas of the esophagus are relatively common in countries in eastern Asia, including China and Japan. They are characterized by poor prognosis and rapid clinical progression with a high frequency of lymph node metastasis and recurrence. Elucidation of the factors affecting invasion and metastasis is very important. We have clarified proliferative activity and p53 status correlate with early invasive trend(1997), expression of MMP-7, 9 and membrane type of MMT is closely associated with invasion depth(2000). Protein tyrosine kinases (PTKs) and phosphatases (PTPs) expression was also surveyed in esophageal cancer cell lines by RT-PCR using degenerated primers (1997, 1999). Now we are planning the new project employing DNA alley analysis system to establish useful biomarkers to predict malignant potential of esophageal cancer.

3. Pathogenesis of chronic inflammatory diseases such as sarcoidosis, ulcerative coltis, and Crohn's disease.

　The causes of sarcoidosis are not known. The DNA of Mycobacterium tuberculosis has been detected in some sarcoid lesions. In Japan, Propionibacterium acnes has been isolated from such lesions, but whether this indigenous bacterium is related to the disease is unclear. Our research has been carried out in order to identify any etiological relationship between sarcoidosis and these bacterial species. Immunopathologically, there were abundant insoluble immune complexes (IgA and/or IgM) in lymph nodes with sarcoidosis, and bacterial components such as muramyl dipeptide and P acnes-specific lipoteichoic acid were accumulated in the site of disease activity. Quantatitative PCR of propionibacterial and mycobacterial DNA in lymph nodes disclosed that all patients with sarcoidosis had many genomes of P acnes or P granulosum: about the same number of M tuberculosis genomes in tuberculosis patients. Antibody titiers agaisnt some of propionibacterial antigens were increased in sarcoidosis patients with significant differences from healthy controls. Antigen-specific mitogenic responses of peripheral blood mononuclear cells were induced in sarcoidosis patients but not in healthy controls, when recombinant proteins or synthetic peptides derived from a propionibacterial 79kDa antigen, which amino acid sequences showed high score of homology to mycobacterial trigger factor, were used as stimulators. Disease related to bacteria can arise from infections that are endogenous or exogenous. People with sarcoidosis may have an allergic condition (Coomb's type IV hypersensitivity) against some antigen of propionibacteria. Finally, sarcoidosis may have no single causative agent, but multiple agents. An international cooperative study with quantitative PCR may help to answer the questions about the causes.

　

Publications (selected papers, 2000〜2002)

　 1. Kobayshi D, Eishi Y, Ohkusa T, Ishige I, Suzuki T, Minami J, Yamada T, Takizawa T, Koike M Gastric mucosal density of Helicobacter pylori estimated by real-time PCR compared with results of urea breath test and histological grading. J. Med. Microbiol. 2002; 51: 1-7.

　 2. Bai YQ, Yamamoto H, Akiyama Y, Tanaka H, Takizawa T, Koike M, Kenji Yagi O, Saitoh K, Takeshita K, Iwai T, Yuasa Y. Ectopic expression of homeodomain protein CDX2 in intestinal metaplasia and carcinomas of the stomach. Cancer Lett. 2002 Feb 8;176(1):47-55.

　 3. Eishi Y, Suga M, Ishige I, Kobayashi D, Yamada T, Takemura T, Takizawa T, Koike M, Kudoh S, Costabel U, Guzman J, Rizzato G, Gambacorta M, du Bois R, Nicholson AG, Sharma OP, Ando M. Quantitative analysis of mycobacterial and propionibacterial DNA in lymph nodes of Japanese and European patients with sarcoidosis. J Clin Microbiol. 2002 Jan;40(1):198-204.

　 4. Mikami S, Ohashi K, Usui Y, Nemoto T, Katsube K, Yanagishita M, Nakajima M, Nakamura K, Koike M. Loss of syndecan-1 and increased expression of heparanase in invasive esophageal carcinomas. Jpn J Cancer Res. 2001 Oct;92(10):1062-73.

　 5. Shiraishi J, Utsuyama M, Akashi T, Nemoto T, Ohashi K, Akamatsu H, Sunamori M, Kitagawa M, Hirokawa K. Immunohistological analysis of thymoma by molecules differentially expressed in the thymic cortex and medulla, and its application in the differential diagnosis of thymoma from esophageal and lung cancer. Pathol Res Pract. 2001;197(9):611-9.

　 6. Edamatsu H, Gau CL, Nemoto T, Guo L, Tamanoi F. Cdk inhibitors, roscovitine and olomoucine, synergize with farnesyltransferase inhibitor (FTI) to induce efficient apoptosis of human cancer cell lines. Oncogene. 2000 Jun 22; 19(27):3059-68.

　 7. Nonomura Y, Yasumoto M, Yoshimura R, Haraguchi K, Ito S, Akashi T, Ohashi I. Relationship between bone marrow cellularity and apparent diffusion coefficient. J Magn Reson Imaging. 2001 May;13(5):757-60.

　 8. Ohashi K, Nemoto T, Nakamura K, Nemori R. Increased expression of matrix metalloproteinase 7 and 9 and membrane type 1-matrix metalloproteinase in esophageal squamous cell carcinomas. Cancer. 2000 May 15;88(10):2201-9.

　 9. Koseki K, Takizawa T, Koike M, Ito M, Nihei Z, Sugihara K. Distinction of differentiated type early gastric carcinoma with gastric type mucin expression. Cancer. 2000 Aug 15;89(4):724-32.

　10. Warabi M, Nemoto T, Ohashi K, Kitagawa M, Hirokawa K. Expression of protein tyrosine phosphatases and its significance in esophageal cancer. Exp Mol Pathol. 2000 Jun;68(3):187-95.

　11. Akashi T, Ito E, Eishi Y, Koike M, Nakamura K, Burgeson RE. Reduced expression of laminin alpha 3 and alpha 5 chains in non-small cell lung cancers. Jpn J Cancer Res. 2001 Mar;92(3):293-301.

　12. Horiuchi T, Ohkusa T, Watanabe M, Kobayashi D, Miwa H, Eishi Y. Helicobacter pylori DNA in drinking water in Japan. Microbiol Immunol. 2001;45(7):515-9.

　13. Ohkusa T, Fujiki K, Takashimizu I, Kumagai J, Tanizawa T, Eishi Y, Yokoyama T, Watanabe M. Improvement in atrophic gastritis and intestinal metaplasia in patients in whom Helicobacter pylori was eradicated. Ann Intern Med. 2001 Mar 6;134(5):380-6.

　14. Ebe Y, Ikushima S, Yamaguchi T, Kohno K, Azuma A, Sato K, Ishige I, Usui Y, Takemura T, Eishi Y. Proliferative response of peripheral blood mononuclear cells and levels of antibody to recombinant protein from Propionibacterium acnes DNA expression library in Japanese patients with sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 2000 Oct;17(3):256-65.

　15. Ohkusa T, Fujiki K, Takashimizu I, Kumagai J, Tanizawa T, Eishi Y. Endoscopic and histological comparison of nonulcer dyspepsia with and without Helicobacter pylori infection evaluated by the modified Sydney system. Am J Gastroenterol. 2000 Sep;95(9):2195-9.

　16. Kato C, Sato K, Wakabayashi A, Eishi Y. The effects of allopurinol on immune function in normal BALB/c and SCID mice. Int J Immunopharmacol. 2000 Jul;22(7):547-56.

　17. Mimura M, Tanaka N, Kimijima Y, Eishi Y, Amagasa T, Okada N. Melanotic neuroectodermal tumor of infancy -immunohistochemical and ultrastructural study-. Asian J Oral Maxillofac Surg 2000; 12: 217-224

　18. Ueno T, Toi M, Saji H, Muta M, Bando H, Kuroi K, Koike M, Inadera H, Matsushima K : The role of macrophage chemoattractant protein-1 in macrophage recruitment, angiogenesis and survival of human breast cancer. Clin Cancer Res 6: 3282-3289, 2000.

　19. Ueno T, Toi M, Koike M, Nakamura S, Tominaga T. Tissue factor expression in breast cancer tissues: its correlation with prognosis and plasma concentration Br J Cancer 83: 164-70, 2000.

　

[Graduate School, School of Medicine]

［TOKYO MEDICAL AND DENTAL UNIVERSITY］