Abstract: |
Background: Neuroblastoma is the most common solid extracranial tumor in childhood, still with poor survival rates for metastatic disease. Neuroblastoma cells are of neuroectodermal origin and express a number of cancer germline (CG) antigens. These CG antigens may represent a potential target for immunotherapy such as peptide-based vaccination strategies. Objective: The purpose of this study was to analyze the presence of MAGE-A1, MAGE-A3/A6, and NY-ESO-1 on an mRNA and protein level and to determine the expression of MHC class I and MHC class II antigens within the same tumor specimens. Methods: A total of 68 tumors were available for RT-PCR, and 19/68 tumors were available for immunohistochemical (IHC) analysis of MAGE-A1, MAGE-A3/A6, and NY-ESO-1. In parallel, the same tumors were stained with a panel of antibodies for MHC class I and MHC class II molecules. Results: Screening of 68 tumor specimens by RT-PCR revealed expression of MAGE-A1 in 44%, MAGE-A3/ A6 in 21%, and NY-ESO-1 in 28% of cases. Immunohistochemistry for CG antigens of selected tumors showed good agreement between protein and gene expression. However, staining revealed a heterogeneous expression of CG antigens. None of the selected tumors showed MHC class I or MHC class II expression. Conclusions: mRNA expression of MAGE-A1, MAGE-A3/A6, and NY-ESO-1 is congruent with the protein expression as determined by immunohistochemistry. The heterogeneous CG-antigen expression and the lack of MHC class I and II molecules may have implications for T-cell-mediated immunotherapy in neuroblastoma. © Springer-Verlag 2004. |
Keywords: |
immunohistochemistry; controlled study; human tissue; protein expression; unclassified drug; human cell; antigen expression; protein analysis; reverse transcription polymerase chain reaction; gene expression; neoplasm proteins; membrane proteins; tumor antigen; immunoenzyme techniques; gene expression regulation, neoplastic; immunotherapy; antigens, neoplasm; tissue distribution; neuroblastoma; messenger rna; reverse transcriptase polymerase chain reaction; rna, messenger; melanoma antigen 1; melanoma antigen 3; major histocompatibility antigen class 2; immunoassay; major histocompatibility complex; genes, mhc class ii; antibody; testis; major histocompatibility antigen class 1; ny-eso-1; mage; genes, mhc class i; cancer germline antigens; mhc expression; antigen ny eso 1
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