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

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.

High Levels of Class I Major Histocompatibility Complex mRNA Are Present in Epstein–Barr Virus-Associated Gastric Adenocarcinomas

“…That study also did not look for changes in any of the other MHC-I components that we investigated here. Interestingly, contradictory effects of EBV on expression of the MHC-I apparatus in nasopharyngeal carcinomas have similarly been reported [24,40,41]. Given the systematic upregulation of mRNA levels encoding MHC-I components, our results contradict existing paradigms of virally mediated immune evasion and suggest that in the context of an actual in vivo human tumor setting, the presence of EBV results in increased expression of mRNA encoding MHC-I-dependent antigen presentation components in GCs.…”

Cancer cell‐secreted proteomes as a basis for searching potential tumor markers: Nasopharyngeal carcinoma as a model

“…The secreted cellular proteins, such as soluble interleukin-2 receptors [35], transforming growth factor b1 [36], b-2-microglobulin [27], vascular endothelial growth factor [37], and serum amyloid A protein [38], have been proposed as possible biomarkers. b-2-Microglobulin is the only protein proven to be derived from tumor cells [39], but the levels of serum b-2-microglobulin in NPC patients were not significantly different than those of healthy controls [27]. The three molecules identified in this study were significantly present in serum samples of NPC patients and directly secreted from the tumor cells.…”

High MHC-II expression in Epstein–Barr virus-associated gastric cancers suggests that tumor cells serve an important role in antigen presentation

“…However, immunohistochemical analyses of EBVaGCs observed high levels of at least HLA-DR and HLA-DP protein 41,42,47 , and the coordinated regulation of these genes suggests that the other MHC-II molecules will be similarly present. EBV-positive nasopharyngeal carcinomas frequently express high levels of HLA-DR protein as well 69 . Thus, it seems likely that the level of expression of EBV encoded antagonists of MHC-II dependent antigen presentation is not sufficient to grossly impact the MHC-II presentation system in EBVaGCs and perhaps other EBV-associated carcinomas.…”