Loss of caspase-8 expression does not correlate with MYCN amplification, aggressive disease, or prognosis in neuroblastoma

Cancer Res. 2006 Oct 15;66(20):10016-23. doi: 10.1158/0008-5472.CAN-05-4079.


Inactivation of caspase-8 because of aberrant gene methylation has been associated with amplification of the MYCN oncogene and aggressive disease in neuroblastoma, suggesting that caspase-8 may function as tumor suppressor. However, the prognostic effect of caspase-8 in neuroblastoma has remained obscure. Therefore, we investigated caspase-8 expression and its correlation with established prognostic markers and survival outcome in a large cohort of neuroblastoma patients. Here, we report that loss of caspase-8 protein expression occurs in the majority (75%) of neuroblastoma and is not restricted to advanced disease stages. Surprisingly, no correlation was observed between caspase-8 expression and MYCN amplification. Similarly, ectopic expression of MYCN or antisense-mediated down-regulation of MYCN had no effect on caspase-8 expression in neuroblastoma cell lines. In addition, caspase-8 expression did not correlate with other variables of high-risk disease (e.g., 1p36 aberrations, disease stage, age at diagnosis, or tumor histology). Most importantly, loss of caspase-8 protein had no effect on event-free or overall survival in the overall study population or in distinct subgroups of patients. By revealing no correlation between caspase-8 expression and MYCN amplification or other established variables of aggressive disease, our findings in a large cohort of neuroblastoma patients show that inactivation of caspase-8 is not a characteristic feature of aggressive neuroblastoma. Thus, our study provides novel insight into the biology of this tumor, which may have important clinical implications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alstrom Syndrome
  • Blotting, Western
  • Caspase 8 / biosynthesis*
  • Caspase 8 / genetics
  • Cell Line, Tumor
  • DNA Methylation
  • Disease Progression
  • Gene Amplification
  • Gene Expression Profiling
  • Genes, myc*
  • Humans
  • N-Myc Proto-Oncogene Protein
  • Neuroblastoma / enzymology*
  • Neuroblastoma / genetics
  • Neuroblastoma / pathology
  • Nuclear Proteins / biosynthesis
  • Nuclear Proteins / genetics
  • Oligonucleotide Array Sequence Analysis
  • Oncogene Proteins / biosynthesis
  • Oncogene Proteins / genetics


  • MYCN protein, human
  • N-Myc Proto-Oncogene Protein
  • Nuclear Proteins
  • Oncogene Proteins
  • Caspase 8