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Multiplex ligation-dependent probe amplification equals fluorescence in-situ hybridization for the identification of patients at risk for metastatic disease in uveal melanoma

Vaarwater, Jolandaa,b; van den Bosch, Thomasb,d; Mensink, Hanneke W.d; van Kempen, Chantalb; Verdijk, Rob M.c; Naus, Nicole C.a; Paridaens, Diond,e; Brüggenwirth, Hennie T.b; Kiliç, Eminea; de Klein, Anneliesb

doi: 10.1097/CMR.0b013e32834e6a67

In uveal melanoma, loss of chromosome 3 and gain of chromosome 8q are associated with a high risk of metastasis. In this study, we validated the use of multiplex ligation-dependent probe amplification (MLPA) in detecting patients at risk for metastatic disease in comparison with the predictive power of fluorescence in-situ hybridization (FISH). For 64 uveal melanoma samples, the MLPA results of chromosome 3 and 8 were compared with the results obtained by FISH. For seven samples, a single nucleotide polymorphism array was performed to clarify discrepancies. Clinical information together with the histopathology and chromosomal aberrations of chromosomes 1, 3, 6, and 8 were evaluated for correlation with the patients’ prognosis. Loss of chromosome 3, loss or gain of 8p, and gain of 8q, found with MLPA, correlated with a significantly lower disease-free survival (P<0.001). On the basis of the clinical outcome, 12 patients would have been classified incorrectly using MLPA results of chromosomes 3 and 8. FISH results led to the same incorrect classification. Four patients with abnormalities of chromosomes 3 and 8 in the tumor, detected with MLPA, are still alive without metastasis. Eight patients without concurrent aberrations of chromosomes 3 and 8 in the tumors died due to metastasis. The sensitivity of MLPA to detect patients at risk for metastatic disease is higher than with the results obtained with FISH (0.795 vs. 0.692). The specificity is equal for both techniques (0.840). MLPA is able to detect patients at risk for metastasis using the results for chromosomes 3 and 8. There is no significant difference in the predictive power of MLPA compared with FISH.

aDepartments of Ophthalmology

bClinical Genetics

cPathology, Erasmus MC Rotterdam

dRotterdam Eye Hospital, the Netherlands

eDepartment of Ophthalmology, Geneva University Hospital, Switzerland

Supplementary material in form of an appendix can be requested from

Correspondence to Dr Annelies de Klein, PhD, Department of Clinical Genetics, Room Ee9.16, PO Box 2040, 3000 CA Rotterdam, the Netherlands Tel: +31 0 10 7044153; fax: +31 0 10 7044736; e-mail:

Received April 1, 2011

Accepted October 21, 2011

© 2012 Lippincott Williams & Wilkins, Inc.