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

Abstract

Aims - Overexpression of c-myc protein has independent prognostic significance in a variety of primary and metastatic cutaneous melanomas which suggests a possible role for this gene in melanoma-genesis. We have therefore examined the importance of this oncogene in uveal melanoma and studied the coexpression 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 estimated by flow cytometric analysis of nuclei extracted from paraffin blocks. The expression of Bcl-2 and p53 protein was assessed by immunohistochemistry. A total of 71 tumours were studied and the results compared with survival 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 regression 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 positive 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 inactivation/mutation. Although Bcl-2 is unlikely to have any effect on tumour growth or metastasis, it could contribute to the general lack of susceptibility to apoptosis in these tumours.