The relation between c-myc expression and interferon sensitivity in uveal melanoma

Br J Ophthalmol. 2004 Dec;88(12):1563-7. doi: 10.1136/bjo.2003.033498.

Abstract

Background/aim: Interferons (IFN) are currently being used to treat melanoma, including some patients with uveal melanoma. IFN is thought to inhibit tumour growth through downregulation of the c-myc oncogene; the overexpression of which has been shown to be associated with resistance in cell lines. The aim of this study was to investigate the relation between c-myc gene expression and IFN sensitivity in a series of uveal melanomas in a short term chemosensitivity assay.

Methods: Tumours from 45 patients with uveal melanoma who had undergone enucleation were studied. The ATP chemosensitivity assay was used to study sensitivity to IFN-alpha-2b in freshly isolated cells from each tumour. Flow cytometry was used to assess c-myc expression in formalin fixed material from the primary specimens.

Results: There was a wide range of IFN sensitivity between the specimens whereas c-myc expression was universal and present in 80% of the tumour cells in 80% of the specimens. Higher c-myc expression was associated with IFN-alpha resistance as measured by the maximum percentage of inhibition (p = 0.05) and there was a trend with the IFN sensitivity index (p = 0.07).

Conclusions: These results demonstrate that tumours with high c-myc expression are also associated with IFN resistance. Future research is required to explore the potential of c-myc gene manipulation combined with IFN therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use*
  • Dose-Response Relationship, Drug
  • Female
  • Flow Cytometry / methods
  • Gene Expression / genetics
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / therapeutic use*
  • Male
  • Melanoma / drug therapy*
  • Melanoma / genetics
  • Melanoma / pathology
  • Middle Aged
  • Proto-Oncogene Proteins c-myc / analysis*
  • Recombinant Proteins
  • Tumor Cells, Cultured
  • Uveal Neoplasms / drug therapy*
  • Uveal Neoplasms / genetics
  • Uveal Neoplasms / pathology

Substances

  • Antineoplastic Agents
  • Interferon alpha-2
  • Interferon-alpha
  • Proto-Oncogene Proteins c-myc
  • Recombinant Proteins