c-myc copy number gains in bladder cancer detected by fluorescence in situ hybridization

Am J Pathol. 1995 May;146(5):1131-9.


Amplification and overexpression of c-myc have been suggested as prognostic markers in human cancer. To assess the role of c-myc gene copy number alterations in bladder cancer, 87 bladder tumors were examined for c-myc aberrations by fluorescence in situ hybridization. Dual labeling hybridization with a repetitive pericentromeric probe specific for chromosome 8 and a probe for the c-myc locus (at 8q24) was performed to analyze c-myc copy number in relation to chromosome 8 copy number on a cell by cell basis. A clear-cut c-myc amplification (up to 40 to 150 copies per cell) was found in 3 tumors. There was a low level c-myc copy number increase in 32 of the remaining 84 tumors. There was no association of low level c-myc copy number increase with c-myc protein overexpression. This suggests that a c-myc gene copy number gain as detected by fluorescence in situ hybridization does not necessarily reflect a disturbed c-myc gene function but may indicate a structural chromosome 8 abnormality including gain of distal 8q. The strong association of low level c-myc (8q) gains with tumor grade (P < 0.0001), stage (P < 0.0001), chromosome polysomy (P < 0.0001), p53 protein expression (P = 0.0019), p53 deletion (P = 0.0403), and tumor cell proliferation (Ki67 labeling index; P = 0.0021) is consistent with a role of chromosome 8 alterations in bladder cancer progression.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Chromosomes, Human, Pair 8
  • Gene Amplification / genetics*
  • Genes, myc / genetics*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Ki-67 Antigen
  • Neoplasm Proteins / analysis
  • Neoplasm Staging
  • Nuclear Proteins / analysis
  • Proto-Oncogene Proteins c-myc / biosynthesis*
  • Tumor Suppressor Protein p53 / analysis
  • Urinary Bladder Neoplasms / metabolism*


  • Ki-67 Antigen
  • Neoplasm Proteins
  • Nuclear Proteins
  • Proto-Oncogene Proteins c-myc
  • Tumor Suppressor Protein p53