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

• Published in: British journal of ophthalmology Vol. 98; no. 6; pp. 769 - 774
• Main Authors: Cassoux, Nathalie, Rodrigues, Manuel Jorge, Plancher, Corine, Asselain, Bernard, Levy-Gabriel, Christine, Lumbroso-Le Rouic, Livia, Piperno-Neumann, Sophie, Dendale, Rémi, Sastre, Xavier, Desjardins, Laurence, Couturier, Jérôme
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group LTD 01.06.2014; BMJ Publishing Group
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Arrays; Artificial chromosomes; Chromosome Deletion; Chromosomes, Human, Pair 3 - genetics; Chromosomes, Human, Pair 8 - genetics; Classification; Clinical Science; Comparative Genomic Hybridization - methods; Deoxyribonucleic acid; DNA; Female; Gene expression; Gene Expression Profiling; Genomes; Histology; Humans; Liver; Male; Medical prognosis; Melanoma; Melanoma - diagnosis; Melanoma - genetics; Melanoma - secondary; Metastasis; Middle Aged; Monosomy; Oligonucleotide Array Sequence Analysis; Prognosis; Proportional Hazards Models; Prospective Studies; Software; Statistical analysis; Studies; Tumors; Ultrasonic imaging; Uveal Neoplasms - diagnosis; Uveal Neoplasms - genetics; Uveal Neoplasms - secondary; Young Adult; Pathology; Choroid; Genetics; Diagnostic tests/Investigation
• ISSN: 0007-1161; 1468-2079
• DOI: 10.1136/bjophthalmol-2013-303867

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.