The relation between c-myc expression and interferon sensitivity in uveal melanoma.
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.
Tulley
P N
PN
RAFT Institute of Plastic Surgery, Mount Vernon Hospital, Northwood, Middlesex HA6 2JR, UK. paultulley@hotmail.com
Neale
M
M
Jackson
D
D
Chana
J S
JS
Grover
R
R
Cree
I
I
Grobbelaar
A O
AO
Wilson
G D
GD
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
D000970:Antineoplastic Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D016271:Proto-Oncogene Proteins c-myc; D011994:Recombinant Proteins