The relation between c-myc expression and interferon sensitivity in uveal melanoma
- 1RAFT Institute of Plastic Surgery, Mount Vernon Hospital, Northwood, Middlesex, HA6 2JR, UK
- 2Gray Cancer Institute, Mount Vernon Hospital, Northwood, Middlesex, UK
- 3Institute of Opthalmology, City Road, London, UK
- Correspondence to: Mr Paul N Tulley RAFT Institute of Plastic Surgery, Mount Vernon Hospital, Northwood, Middlesex, HA6 2JR, UK; paultulleyhotmail.com
- Accepted 31 January 2004
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-α-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-α 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.
- CAM, complete assay medium
- CTL, cytotoxic T lymphocyte
- FITC, fluorescein isothiocyanate
- HLA, histocompatibility antigen
- IFN, interferons
- LTR, long terminal repeat
- MI, maximal inhibitor
- NK, natural killer
- PBS, phosphate buffered saline
- RLU, relative light units
- c-myc
- uveal melanoma
- interferon
- chemosensitivity
- CAM, complete assay medium
- CTL, cytotoxic T lymphocyte
- FITC, fluorescein isothiocyanate
- HLA, histocompatibility antigen
- IFN, interferons
- LTR, long terminal repeat
- MI, maximal inhibitor
- NK, natural killer
- PBS, phosphate buffered saline
- RLU, relative light units
- c-myc
- uveal melanoma
- interferon
- chemosensitivity







