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

• Published in: British journal of ophthalmology Vol. 83; no. 1; pp. 110 - 114
• Main Authors: Chana, J S, Wilson, G D, Cree, I A, Alexander, R A, Myatt, N, Neale, M, Foss, A J E, Hungerford, J L
• Format: Journal Article
• Language: English
• Published: BMA House, Tavistock Square, London, WC1H 9JR BMJ Publishing Group Ltd 01-01-1999; BMJ; BMJ Publishing Group LTD
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Antigens; Apoptosis; Bcl-2; Biological and medical sciences; c-myc; Child; Chromosomes; Clinical outcomes; Female; Flow cytometry; Histopathology; Humans; Immunohistochemistry; Influence; Male; Medical prognosis; Medical sciences; Melanoma; Melanoma - genetics; Melanoma - metabolism; Melanoma - therapy; Metastasis; Middle Aged; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Ophthalmology; Original articles - Laboratory science; p53; Prognosis; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-bcl-2 - metabolism; Proto-Oncogene Proteins c-myc - genetics; Proto-Oncogene Proteins c-myc - metabolism; Radiation therapy; Skin cancer; Studies; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; Tumors; Uvea diseases; uveal melanoma; Uveal Neoplasms - genetics; Uveal Neoplasms - metabolism; Uveal Neoplasms - therapy; Human; Immunohistochemistry; Pathology; Eye disease; TP53 Gene; Uvea; Malignant melanoma; Exploration; Uvea disease; Malignant tumor; Gene expression
• ISSN: 0007-1161; 1468-2079
• DOI: 10.1136/bjo.83.1.110

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.