c-myc, p53, and Bcl-2 expression and clinical outcome in uveal melanoma

Aims-Overexpression of c-myc protein has independent prognostic significanc e in a variety of primary and metastatic cutaneous melanomas which suggests a possible role for this gene in melanomagenesis. We have therefore examin ed the importance of this oncogene in uveal melanoma and studied the coexpr ession of two other gene products, Bcl-2 and p53, which might contribute to its effect. Methods-The percentage of cells positive for nuclear c-myc expression was e stimated by flow cytometric analysis of nuclei extracted from paraffin bloc ks. The expression of Bcl-2 and p53 protein was assessed by immunohistochem istry. A total of 71 tumours were studied and the results compared with sur vival with a mean follow up period of 6 years. Results-c-myc was expressed in >50% of the cells by 70% of the tumours, and was independently associated with improved survival in a Cox multiple regr ession model. Although Bcl-2 was expressed by the majority of the cells in 67% tumours, it was without effect on prognosis. None of the cases studied showed convincing positivity for p53. Analysis of coexpression showed that the best survival was seen in c-myc+/Bcl-2+ tumours and the worst in c-myc- /Bcl-2- tumours. Conclusion-The finding of improved rather than reduced survival in c-myc po sitive tumours is at variance with skin melanoma. There was no evidence to suggest that c-myc was modulated by upregulation of Bcl-2 or p53 inactivati on/mutation. Although Bcl-2 is unlikely to have any effect on tumour growth or metastasis, it could contribute to the general lack of susceptibility t o apoptosis in these tumours.