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

Abstract

Purpose: 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.

Patients and methods: 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.

Results: 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.

Conclusion: 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.