Translating Uveal Melanoma Cytogenetics Into Clinical Care
Archives of Ophthalmology
Objective: To report our experience in translating uveal melanoma cytogenetics to routine clinical practice. Methods: 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
... nformation from smaller samples. In 2007, we extended this service to patients undergoing radiotherapy or phototherapy. Results: Initial expectations regarding the sensitivity and specificity of monosomy 3 tests in predicting metastatic death were found to be overoptimistic. Cytogenetic clas-sification 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. Conclusion: 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.