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Originally published In Press as doi:10.1167/iovs.08-3165 on January 31, 2009
 (Investigative Ophthalmology and Visual Science. 2009;50:3048-3055.)
© 2009 by The Association for Research in Vision and Ophthalmology, Inc.
doi:10.1167/iovs.08-3165
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Multiplex Ligation-Dependent Probe Amplification of Uveal Melanoma: Correlation with Metastatic Death

Bertil Damato,1 Justyna Dopierala,2 Annelies Klaasen,3 Marcory van Dijk,4 Julie Sibbring,5 and Sarah E. Coupland2

1From the Liverpool Ocular Oncology Centre, St. Paul’s Eye Clinic, Royal Liverpool University Hospital, Liverpool, United Kingdom; the 2Department of Pathology, University of Liverpool, Liverpool, United Kingdom; the 3Department of Pathology, University Medical Centre Nijmegen, Nijmegen, The Netherlands; the 4Department of Pathology, University Hospital Groningen, Groningen, The Netherlands; and the 5Molecular Genetic Department, Liverpool Women’s Hospital, Liverpool, United Kingdom.

PURPOSE. To evaluate multiplex ligation-dependent probe amplification (MLPA) of uveal melanoma as a predictive tool for metastatic death.

METHODS. Uveal melanoma specimens of 73 patients treated between 1998 and 2000 were included. DNA samples were analyzed with MLPA evaluating 31 loci on chromosomes 1, 3, 6 and 8, and the results were correlated with metastatic death.

RESULTS. The patients (27 women; 46 men) had a median age of 60.6 years and a median follow-up of 6.2 years. Metastatic death occurred in 28 patients, correlating most strongly with chromosome 3 losses and gains on 8q (Cox univariate analysis, P < 0.001). Chromosome 6, region p25, gains correlated with good survival (Cox univariate analysis, P = 0.003). Prediction of metastatic death was improved by considering equivocal chromosome 3 losses as abnormal and by taking account of multiple risk factors, such as 8q gains, tumor diameter, and histologic features indicative of high-grade malignancy.

CONCLUSIONS. MLPA analysis of uveal melanoma predicts metastatic death if statistically insignificant losses of chromosome 3 are considered together with gains in 8q as well as clinical stage and histologic grade of malignancy.




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