c-myc, p53, and Bcl-2 expression and clinical outcome in uveal melanoma
- J S Chanaa,
- G D Wilsonb,
- I A Creec,
- R A Alexanderc,
- N Myattc,
- M Nealec,
- A J E Fossd,
- J L Hungerforde
- aRAFT Institute of Plastic Surgery, bGray Laboratory, Mount Vernon Hospital, Northwood, Middlesex HA6 2JR, cDepartment of Pathology, Institute of Ophthalmology, University College London, London EC1V 9EL, dDepartment of Ophthalmology, Queens Medical Centre, Nottingham NG7 2UH, eMoorfields Eye Hospital, London EC1V 2PD
- Dr I A Cree, Department of Pathology, Institute of Ophthalmology University College London, Bath Street, London EC1V 9EL.
- Accepted 12 May 1998
Abstract
AIMS Overexpression ofc-myc protein has independent prognostic significance in a variety of primary and metastatic cutaneous melanomas which suggests a possible role for this gene in melanomagenesis. 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-mycexpression was estimated by flow cytometric analysis of nuclei extracted from paraffin blocks. The expression ofBcl-2 and p53protein 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-mycwas 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 inc-myc+/Bcl-2+ tumours and the worst inc-myc−/Bcl-2−tumours.
CONCLUSION The finding of improved rather than reduced survival inc-myc positive tumours is at variance with skin melanoma. There was no evidence to suggest thatc-myc was modulated by upregulation ofBcl-2 or p53inactivation/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.








