Genome-wide profiling is a clinically relevant and affordable prognostic test in posterior uveal melanoma

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Abstract

Objective

This study investigated the capacity of genetic analysis of uveal melanoma samples to identify high-risk patients and discusses its clinical implications.

Methods

Patients with posterior uveal melanoma were prospectively enrolled. Tumour samples were derived from enucleated globe, fine-needle aspirates or endoresection. Chromosome 3 and 8 status was determined by array comparative genomic hybridisation (array-CGH). Patients were followed after treatment to detect metastasis.

Results

Four groups were classified by array-CGH. Patients were divided into disomy 3 and normal chromosome 8 (D3/8nl), disomy 3 and 8q gain (D3/8g), monosomy 3 and normal chromosome 8 (M3/8nl) and monosomy 3 and 8 or 8q gain (M3/8g). Median follow-up was 28 months (range: 1–147 months). At the end of the study, 128 patients (33.7%) had developed metastasis and 96 patients had died. Univariate Cox proportional hazard analysis showed that factors associated with metastasis included basal tumour diameter p=0.0007, tumour thickness p=0.01, mixed/epithelioid cell type p=0.0009 and genomic data p<0.0001. High-risk profile was more strongly associated with metastasis than the other prognostic factors p<0.001. Multivariate Cox modelling analysis showed that the status of chromosomes 3 and 8 were the only two variables that independently contributed to prognosis: monosomy 3 alone p=0.001 and monosomy 3 and 8q gain p<0.0001.

Conclusions

Array-CGH allowed identification of three prognostic groups with low, intermediate and high risk of developing metastasis. Array-CGH is a reliable and inexpensive method for uveal melanoma prognosis. This method is now currently used in France.

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