The prognostic value of cyclin D1, p53, and MDM2 protein expression in uveal melanoma

Malignant uveal melanoma is the commonest primary intraocular tumour in adu lts. It metastasizes frequently and 50% of patients die within 10 years of diagnosis. The expression of cyclin D1, p53, and MDM2 in uveal melanoma and their relationship to metastasis-free 5-year survival was determined, in o rder to investigate whether these proteins help to distinguish those patien ts with a favourable prognosis from those with a poorer one. Ninety-six eye s enucleated for uveal melanomas were immunohistochemically analysed for th e protein expression of cyclin D1 and related cell-cycle markers, p53 and M DM2, The evaluation of the specimens was undertaken by two independent path ologists without knowledge of the outcome. Statistical analysis of clinical , morphological, and immunohistological features was performed. A 'favourab le outcome' was defined as survival of at least 5 years after diagnosis, wi thout metastases (n = 57). An 'unfavourable outcome' was defined as death f rom metastases within the first 5 years after diagnosis of meal melanoma (n = 39), Cyclin D1 positivity (>15% positive tumour cells) as well as p53 po sitivity(>15% positive tumour cells) was associated with an unfavourable ou tcome (for cyclin D1: odds ratio = 4.2, 95% confidence interval 1.5-11.8, p = 0.006; for p53: odds ratio = 3.2, 95% confidence interval 1.1-9.3, p = 0 .03). In addition, cyclin D1 positivity was associated with the presence of extraocular extension of the tumour (p = 0.01), with the mixed or epitheli oid cell type (p = 0.02), and with the tumour cell MIB-1 positivity (p = 0. 0001). MDM2 immunoreactivity of the tumour cells showed a potential correla tion with clinical outcome (odds ratio = 2.1, 95% confidence interval 0.8-5 .8, p = 0.13). Multiple logistic regression models showed that cyclin D1 po sitivity is an independent prognostic factor after control for other progno stic markers, The expression of cyclin D1 in uveal melanoma is associated w ith a more aggressive course and histologically unfavourable disease. This could serve as a further independent prognostic factor in uveal melanoma, C opyright (C) 2000 John Wiley & Sons, Ltd.