Significance of gene expression analysis in uveal melanoma in comparison to standard risk factors for risk assessment of subsequent metastases

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Abstract
This study was undertaken to identify and compare the prognostic value of gene expression, chromosomal, and clinico-pathological data for the prediction of subsequent metastases in patients with primary uveal melanoma. For comparison of different sets of predictor variables diagonal linear discriminant analysis was used. Chromosomal events were assessed by comparative genomic hybridization and gene expression profiling by microarray. Twenty-eight patients with a median follow-up of 68 months were analyzed, of whom 12 had developed subsequent metastases. Diagonal linear discriminant analysis with crossvalidation of gene expression data detected 42 genes as differentially expressed in metastasizing vsnon-metastasizing uveal melanomas in all 28 cases. Comparing quantitative scores of discriminant analysis, grouping precision was significant better with gene expression profiling compared to comparative genomic hybridization (P=0.01) and to clinical data (P=0.001). Two published gene lists associated with monosomy 3 and metastatic tumor growth were used as classifier for discriminant analysis and yielded superior classification in patients with and without subsequent metastases than chromosomal or clinico-pathological data. In our patient cohort gene expression profiling of primary uveal melanoma tissue was superior to clinical-pathological and chromosomal analysis to assess for the risk of subsequent metastases.