β2-Microglobulin and HLA-DR Expression in Relation to the Presence of Epstein-Barr Virus in Nasopharyngeal Carcinomas

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Abstract
We have investigated the immunohistochemical expression of β 2-microglobulin and HLA-DR proteins in nasopharyngeal carcinoma (NPC) in relation to the expression of the Epstein-Barr virus (EBV)-encoded EBER 1-2 mRNAs and LMP-1 protein. β2-Microglobulin is expressed in association with MHC-I molecules on most nucleated cells and HLA-DR belongs to the MHC-II molecules which are expressed mostly on antigen-presenting cells. Formalin-fixed paraffin-embedded tissue from 37 NPC cases was stained with immunohistochemistry for β 2-microglobulin, HLA-DR and LMP-1 proteins and by RNA in situ hybridization for EBER 1-2 mRNAs. β 2-Microglobulin-positive staining was found in neoplastic cells in all cases. In 19/37 NPC cases the positive staining was found in most neoplastic cells. In the remaining 18 NPC cases more than 25% of the neoplastic cells showed significantly reduced or negative staining in comparison to the normal epithelium and infiltrating small lymphocytes. HLA-DR-positive staining was found in 27/37 NPC cases. EBER 1 -2 transcripts were deteced in neoplastic cells in 13/37 NPC cases. LMP-1 expression in tumour cells was found in 4/13 EBERl-2-positive cases. No correlation was found between the presence of EBER 1-2 transcripts or LMP-1 protein and the β 2-microglobulin-reduced expression in NPC. Thus, EBV does not seem to use downregulation of MHC-I to avoid the T cell cytotoxic immune response in NPC. HLA-DR expression was observed in all 13 EBV-positive cases of NPC, suggesting that EBV may participate in the induction of HLA-DR expression in a proportion of NPC.

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