The role of HTLV-1 and EBV infection on the development of malignant lymphoma in Okinawa

Research Project

Project/Area Number	11670179
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Single-year Grants
Section	一般
Research Field	Human pathology
Research Institution	Faculty of Medicine, University of the Ryukyus
Principal Investigator	TODA Takayoshi University of the Ryukyus, Faculty of Med. Dept. of Clin. Lab., Med. Associate Professor, 医学部, 助教授 (30108295)
Co-Investigator(Kenkyū-buntansha)	MASUDA Masato University of the Ryukyus, Faculty of Med. Dept. of Int. Med, Lecturer, 医学部・附属病院, 講師 (30295323) UEZATO Hiroshi University of the Ryukyus, Faculty of Med. Dept. of Dermatol. Associate Professor, 医学部, 助教授 (60160157) OSHIMA Koichi Faculty of Med. Dept. of Pathol, Fukuoka Univ. Associate Professor, 医学部, 助教授 (50203766) OKU Hirosuke University of the Ryukyus, Center of molecular bioscience, Division of molecular biotechnology, proffesor, 遺伝子実験センター, 教授 (10177165)
Project Period (FY)	1999 – 2001
Project Status	Completed (Fiscal Year 2001)
Budget Amount *help	¥2,200,000 (Direct Cost: ¥2,200,000) Fiscal Year 2001: ¥500,000 (Direct Cost: ¥500,000) Fiscal Year 2000: ¥900,000 (Direct Cost: ¥900,000) Fiscal Year 1999: ¥800,000 (Direct Cost: ¥800,000)
Keywords	HTLV-1 / EBV / Malignant Lymphoma / Lymph node / Skin / Subtropical area / Okinawa
Research Abstract	In the first part of this study, we studied EBV and HTLV-1 infection in 100 cases of malignant nodal lymphoma. Using polymerase chain reaction (PCR), EBV was detected in 91.7% Hodgkin's lymphoma(HL) and in 64.8% Non-Hodgkin's(NHL), while HTLV-1 was detected in 26.1% NHL. Clonal integration of HTLV-1 was detected in 43.5% HTLV-1 positive cases by Inverse PCR technique. The EBV-infected cells were detected by EBER-1 in situ hybridization in 91.7% HL cases and in 72.7% NHL cases. Irrespective of phenotype and tissue type of the malignant lymphoma, the positlvity rate for EBV infection in Okinawa was higher than that in any other districts reported in Japan. In the second part of this study, we examined the role of HTLV-1 and EBV infection in malignant cutaneous T-cell lymphoma(CTL). A total of 41 cases out of 200 cases, which were suitable for PCR analysis, were selected for analysis. HTLV-1 was positve in 11 of 26 cases and EBV was positive in 10 of 11 HTLV-1 positive cases. On the other hand, EBV was also positive in 12 of 15 HTLV-1 negative cases. These results suggest that HTLV-1 and EBV infection has no significant synergistic effect to the oncogenesis of ATLL. In the third part of this study, we analysed the pathogenetic relationship between EBV infection rate, prognosis, and clinical subtypes of HTLV-1 positive CTL cases. Average life span was 40.6 months and 48.5 months in EBV positive case and EBV negative cases, respectively. These results suggest no significant synergistic association between average life span and EBV infection in HTLV-1 positive CTL. Furthermore, EBV was positive in all cases of tumor and lymphoma types of HTLV-1 positive CTL. This characteristic high positive rate of EBV infection in malignant nodal and cutaneous lymphoma in Okinawa can be ascribed to various factors such as racial and geographical differences.