Multiplex Ligation-Dependent Probe Amplification of Uveal Melanoma: Correlation with Metastatic Death

¹ St Paul's Eye Unit, Royal Liverpool University Hospital, Liverpool, United Kingdom
² Department of Pathology, University of Liverpool, Liverpool , Merseyside, United Kingdom
³ Department of Pathology, University Medical Centre Nijmegen, Nijmegen, Netherlands
⁴ Department of Pathology, University Hospital Groningen, Groningen, Netherlands
⁵ Molecular Genetic Department, Liverpool Women's Hospital, Liverpool, United Kingdom
⁶ Department of Pathology, University of Liverpool, Liverpool, United Kingdom

^* To whom correspondence should be addressed. E-mail: bertil.damato{at}btinternet.com.

	Abstract

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 female; 46 male) 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 chromosome 8q gains (Cox univariate analysis, p<0.001). Chromosome 6p25 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 chromosome 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 chromosome 8q as well as clinical stage and histologic grade of malignancy.

Key Words: melanoma, molecular biology, in situ hybridization, metastasis, multiplex ligation-dependent probe amplification

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