title: The relation between c-myc expression and interferon sensitivity in uveal melanoma.
abstract: OBJECTIVE
  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.
authors.affiliation: RAFT Institute of Plastic Surgery, Mount Vernon Hospital, Northwood, Middlesex HA6 2JR, UK. paultulley@hotmail.com
authors.forename: P N
authors.initials: PN
authors.lastname: Tulley
authors.forename: M
authors.initials: M
authors.lastname: Neale
authors.forename: D
authors.initials: D
authors.lastname: Jackson
authors.forename: J S
authors.initials: JS
authors.lastname: Chana
authors.forename: R
authors.initials: R
authors.lastname: Grover
authors.forename: I
authors.initials: I
authors.lastname: Cree
authors.forename: A O
authors.initials: AO
authors.lastname: Grobbelaar
authors.forename: G D
authors.initials: GD
authors.lastname: Wilson
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008875:Middle Aged; D016271:Proto-Oncogene Proteins c-myc / Q000032:analysis*; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured; D014604:Uveal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D016271:Proto-Oncogene Proteins c-myc; D011994:Recombinant Proteins