Molecular biologic and pathologic study of Epstein-Barr virus infected lymphepithalial carcinomas in salivary gland

点击翻译按钮获取中文摘要

A total 180 cases of salivary gland lymphoepithelial carcinoma (LEC) were col lected from Russia-Asian countries. Their paraffin blocks of surgical materials were obtained for imunohistochemistry, in-situ hybridization and DNA extractionImmunohistochemically, about 50% of the cases showed positive signals for LMP1 gene products, and 100% of them had EBER-1 RNA signals in tumor cells' nuclei, which suggested a definite EBV infection among salivary LEC cases. From 40 cases of them, the C-terminus of the LMP1 gene was PCR-amplified and direct-sequenced. The results indicated that there were at least two different strains of EBV harboring in salivary LEC and that there were many mutational events in them including the characteristic 30 by delefion. From 12 cases of them, the complete sequence for, the LMP1 gene were obtained, and many and new mutations in addition to those which were already found in nasapharyngeal LEC. The promoter region of the LMP1 gene was also analyzed from 20 cases o … More f them, and all of the cases shared common mutational events in regions which were expected to be associated with transcription factorsOne of the complete sequence obtained as mentioned above were cloned into an expression vector and the constructs were transfected into 293T cells to determine their effectd on the activation of NFkB pathways as well as cell growth. The transfected cells showed significant elevation of NFkB activities and suppressed cell growth, which were also seen in cells transfected with vectors with nasopharyngeal CAO or prototype B95-8. The results indicated that the expression of LMP1 affects transcritption activities in LEC cells but that the overall mutaions found in the present study were not always reasons for the tumorigenesisPrimary cultures for salivary LECs were tried many times. However, the cells were hard to maintain. One of them are growing now and they were characterized by immunofluorescence and PCR to be epithelial and EBV infectedThe results obtained as above has given us a new insight for EBV roles in the pathogenesis of salivary LEC. To this end, it is necessary to carry out further investigations on molecular functions of EBV oncogenes Less