Expression of MHC class I, MHC class II, and cancer germline antigens in neuroblastoma

Cancer Immunol Immunother. 2005 Apr;54(4):400-6. doi: 10.1007/s00262-004-0603-z. Epub 2004 Sep 24.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Genes, MHC Class I*
  • Genes, MHC Class II*
  • Humans
  • Immunoenzyme Techniques
  • Male
  • Melanoma-Specific Antigens
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Neoplasm Proteins / analysis*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Neuroblastoma / diagnosis
  • Neuroblastoma / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Testis / metabolism

Substances

  • Antigens, Neoplasm
  • CTAG1B protein, human
  • MAGEA1 protein, human
  • MAGEA3 protein, human
  • MAGEA6 protein, human
  • Melanoma-Specific Antigens
  • Membrane Proteins
  • Neoplasm Proteins
  • RNA, Messenger