To report our experience in translating uveal melanoma cytogenetics to routine clinical practice.
In 1998, we confirmed that monosomy 3 in uveal melanomas correlates with mortality. In 1999, we started offering all patients treated by enucleation or local resection the possibility of monosomy 3 testing, using fluorescence in situ hybridization. In 2006, we started analyzing tumors with multiplex ligation-dependent probe amplification, which provided more information from smaller samples. In 2007, we extended this service to patients undergoing radiotherapy or phototherapy.
Initial expectations regarding the sensitivity and specificity of monosomy 3 tests in predicting metastatic death were found to be overoptimistic. Cytogenetic classification of uveal melanomas into “lethal” and “nonlethal” types was insufficient for estimating risk of metastasis. Prognostication also required consideration of (1) clinical tumor stage; (2) histologic grading of malignancy; and (3) influence of age and sex on life expectancy. We developed a neural network for such multivariate analysis. Metastatic deaths occurred without monosomy 3, possibly because small deletions were missed or because of tumor heterogeneity.
Genomic typing of uveal melanomas proved more complex than we had anticipated but enabled us to reassure patients with a good prognosis while targeting systemic screening at high-risk cases.