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Originally published In Press as doi:10.1167/iovs.08-2279 on September 29, 2008
 (Investigative Ophthalmology and Visual Science. 2009;50:500-504.)
© 2009 by The Association for Research in Vision and Ophthalmology, Inc.
doi:10.1167/iovs.08-2279
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Chromosome 3 Intratumor Heterogeneity in Uveal Melanoma

Hanneke W. Mensink,1,2 Jolanda Vaarwater,1,2 Emine Kiliç,3 Nicole C. Naus,3 Neeltje Mooy,4 Gre Luyten,3,5 Hennie T. Brüggenwirth,2 Dion Paridaens,1 and Annelies de Klein2

1From the The Rotterdam Eye Hospital, Rotterdam, The Netherlands; and the 2Departments of Clinical Genetics, 3Ophthalmology, and 4Pathology, Erasmus Medical Center, Rotterdam, The Netherlands.

PURPOSE. To investigate the presence of focal or diffuse heterogeneity of monosomy 3 in uveal melanoma, by using fluorescence in situ hybridization (FISH).

METHODS. Direct interphase FISH in a series of 151 uveal melanomas revealed 82 tumors with loss of chromosome 3. Tumors with monosomy 3 were suspected to be heterogeneous if there were low percentages of monosomy 3, triploid clones, inconsistencies between FISH on centromere 3 and the long arm of chromosome 3, or discrepancies between fine-needle–aspiration biopsies (FNABs) and the main tumor. These tumors (n = 16), all choroidal melanomas, were selected and analyzed for intratumor heterogeneity by using FISH on paraffin-embedded tissue sections.

RESULTS. Different sections of each tumor were evaluated with FISH: 6 tumors showed monosomy 3 in the same percentage throughout the tumor, and 10 showed multiple clones with different percentages of monosomy 3. However, these tumors did not show focal heterogeneity with respect to chromosome 3 status, and differences in monosomy 3 distribution between the base and apex of the tumor could not be identified.

CONCLUSIONS. Although a small number of uveal melanomas show heterogeneity for chromosome 3, it does not affect survival. In the presence of triploid clones, the loss of chromosome 3 is more difficult to interpret. In general, tumor biopsies in uveal melanoma provide an accurate prediction of the patient’s prognosis.






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