PROGNOSTIC IMPLICATIONS OF MONOSOMY-3 IN UVEAL MELANOMA

Background A high proportion of patients with uveal melanoma die of me tastatic disease. In a subgroup of uveal melanomas there is the loss o f one chromosome 3, To assess the prognostic implications of this gene tic anomaly, we studied 54 patients for a median of 3 . 4 years. Metho ds 180 patients underwent primary enucleation for malignant uveal mela noma at the Ophthalmology Department of the Universitatskiinikum Essen between 1987 and 1993. Tumour material was available for chromosome a nalysis and DNA preparation from 69 of these patients (for logistic re asons unlikely, we believe, to introduce bias), 15 patients were exclu ded from our study: nine because the methods for assessment of monosom y 3 were unsuccessful; five because of insufficient information about their relapse status; one because histopathological data were incomple te. Of the 54 remaining patients, the tumours of 16 were assessed for copy number of chromosome 3 by karyotype analysis, of 30 by comparativ e genomic hybridisation, and of eight by both techniques. Clinical sta tus was assessed by contact with family doctor or a clinical check up. Statistical analysis was by the log-rank test and Cox proportional-ha zard regression. Findings The tumours of 30 patients had monosomy 3. 1 7 (57%) of these patients relapsed with metastatic disease, and the 3- year relapse-free survival rate was 50%. By contrast, of the 24 patien ts whose tumours had retained both chromosomes 3, none developed metas tatic disease, In univariate analysis monosomy 3 was the most signific ant (p<0 . 0001) predictor of poor prognosis in uveal melanoma, follow ed by tumour location (p<0 . 0007) and tumour diameter (p<0 . 0021). H istopathological subtype, age, sex, extrascleral growth, and tumour th ickness had no additional predictive value. Interpretation In uveal me lanoma, monosomy 3 is a significant predictor of both relapse-free and overall survival.