Expression of nine tumour antigens in a series of human glioblastoma multiforme: interest of EGFRvIII, IL-13Ralpha2, gp100 and TRP-2 for immunotherapy

J Neurooncol. 2007 Jan;81(2):139-48. doi: 10.1007/s11060-006-9220-3. Epub 2006 Sep 27.

Abstract

In this study, we investigated the mRNA and protein expression of nine tumour antigens in human glioblastoma multiforme with a view to their possible use in dendritic cell-based immunotherapy. Expression of ALK, EGFRvIII, GALT3, gp100, IL-13Ralpha2, MAGE-A3, NA17-A, TRP-2 and tyrosinase were studied by real-time RT-PCR on frozen tissues using a series of 47 tumour samples from patients with glioblastoma. Results were compared with non-neoplastic brain expression or glioblastoma samples with very low levels of expression near the limits of detection for EGFRvIII and MAGE-A3, as these latter two antigens were not detected in non-neoplastic brain. Tumour antigens showing a 5-fold increase in mRNA expression were considered as positive, and only antigens displaying an mRNA over-expression in a significant number of cases were analysed by immunohistochemistry on paraffin-embedded sections. Using real time RT-PCR, we found EGFRvIII, gp100, IL-13Ralpha2 and TRP-2 to be positive in 64, 38, 32 and 21% of cases, respectively. While we observed no over-expression for ALK, GALT3 and tyrosinase, 3 samples out of 47 were positive for MAGE-3 and 1 sample for NA17-A. More than 25% of tumour cells showed strong protein expression in 13, 34, 85 and 96% of GBM samples for gp100, TRP-2, EGFRvIII and IL-13Ralpha2, respectively. Interestingly, protein expression of at least 3 antigens was observed in 38% of cases. These results point out the importance of EGFRvIII, IL-13Ralpha2 and, to a less extent gp100 and TRP-2, for developing an immunotherapy strategy against glioblastoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / metabolism*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism*
  • Female
  • Glioblastoma / genetics
  • Glioblastoma / metabolism*
  • Glioblastoma / pathology
  • Humans
  • Immunotherapy
  • Interleukin-13 Receptor alpha2 Subunit / genetics
  • Interleukin-13 Receptor alpha2 Subunit / metabolism*
  • Male
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Middle Aged
  • Prognosis
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survival Rate
  • gp100 Melanoma Antigen

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Interleukin-13 Receptor alpha2 Subunit
  • Membrane Glycoproteins
  • Membrane Proteins
  • PMEL protein, human
  • RNA, Messenger
  • Trp2 protein, vertebrate
  • epidermal growth factor receptor VIII
  • gp100 Melanoma Antigen
  • ErbB Receptors