Detection Of Epstein-Barr Virus In Various Types Of Lymphoma And The Study Of Its Role In Pathogenesis Of Lymphoma

The Epstein-Barr virus (EBV) is a member of the B lymphocr>ptovirus genus of the Y herpesvirus family. EBV does not usually replicate itself in B cells but establishes a latent infection instead. At least 10 genes on its genome can be expressed during latency and several are implicated in the process of transformation. Latent membrane protein 1 (LMP1) encoded by the EBV is a multifunctional protein and is believed to play a crucial role in oncogenesis mediated by this virus. LMP 1 oncogene is proved to induce cell transformation and neoplasm in nude mouse. LMP1 can induce several cellular changes, which is essential for transformation and maturation of B-prolymphocytes and also causes up-regulating of adhesion molecules and some cell-activated molecules in B cell. The most concerned action of LMP 1 on cell is the upregulation of antiapoptotic proteins involving Bcl^ Mcl-1, A20 which protect B lymphocytes from apoptosis. There were reports that LMP1 can inactivate one of cell cycle checkpoints to bring about the aberrance of the fidelity and timing of cell division which were contribute to growth transformation of host cells and perhaps tumorigenesis. Recent studies indicate that LMP1 can have amphibious actions on activating both apoptotic and antiapoptotic gene in host cell. Furthermore, LMP1 was reported to intervene transcription of genes, which regulate cell proliferation, cell cycle arrest, and cell apoptosis simultaneously. Those conclusions above were all drawn from the observation and research of nasopharyngealcarcinoma (NPC). Reports of NPC cases from Canton and Taiwan areas in China showed there were some of deleted LMP1 (del LMP) in nasopharyngeal carcinoma population, comparing to prototype B95.8 LMP1. And these del-LMPl (e.g., CAO-LMP1) is found to be more tumorigenic than B95.8 LMP1 in human epithelial cells. However so far there have been few researches on the role of del LMP1 in the pathogenesis of EBV-associated lymphomas and none of domestic reports. Although some researches suggest studies on del-LMPl may contribute to the illumination of signal transduction of LMP1 and the role of del-LMPl in the pathogenesis of EBV-associated tumors. Researchers has confirmed that in addition to endemic Burkitt's lymphoma and NPC. the list of EBV-associated tumors now includes Hodgkin's lymphoma, post-transplant lymphoproliferative disorders, peripheral T-cell non-Hodgkin's lymphoma. The role of Epstein-Barr virus (EBV) and LMP1 in the pathogenesis of lymphoma has not been well understood and there are few reports about LMP1 variant in lymphoma in Chinese although some progresses have been made in EBV-associated NPC. hi the present study, the expression of Bcl-2. Caspase-3, PCNA and P53 is examined and the data are correlated with the genotype, the EBV status. The presence of EBV is investigated with high-amplifying immunohistochemical analysis for latent membrane protein (LMP)-l and in situ hybridization using an antisense riboprobe to EBV-encoded early RNA (EBER) and PCR to detect sequences variants of LMP1. The aim is to investigate the roles of EBV and LMP1 including del LMP1 in oncogenesis and progression of Hodgkin's lymphoma, non-Hodgkin's lymphoma and its possible pathway, and further to achieve one set of sensitive and reliable method to detect EBV.Materials and Methods:1. Patients: 127 cases of lymphomas were obtained from our affiliated hospitals and otherlocal hospitals from the year of 1991 to 2001. All specimens were fixed in 10% formalin,embedded in paraffin serial sections were stained in hemotoxylin and eosin and for immunohistochemistry. All cases were divided into T- and B- NHL and HL according to their immunophenorypes, then NHL were further sub-grouped into there groups of low, intermediate and high grade according to the revised classification of NHL in National Conference of Chinese Association of Pathology in Chengdu (1985) and related references. Gastrointestinal MALToma (lymphomas of mucosa-associated lymphoid tissue) were divided into two groups of low and high...