IOVS Journal of Experimental Medicine
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(Investigative Ophthalmology and Visual Science. 2006;47:3703-3707.)
© 2006 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.06-0101
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Clinical and Cytogenetic Analyses in Uveal Melanoma

Emine Kilic,1 Walter van Gils,1,2 Elisabeth Lodder,2 H. Berna Beverloo,2 Marjan E. van Til,2 Cornelia M. Mooy,3 Dion Paridaens,4 Annelies de Klein,2 and Gregorius P. M. Luyten1

1From the Departments of Ophthalmology, 2Clinical Genetics, and 3Ophthalmopathology, Erasmus MC, Rotterdam, and the 4Rotterdam Eye Hospital, Rotterdam, The Netherlands.

PURPOSE. Uveal melanoma is one of the most frequently occurring primary intraocular malignancies in the Western world. Cytogenetically these tumors are characterized by typical chromosomal losses and gains, such as loss of 1p, 3, and 6q and gain of 6p and 8q. Whereas most studies focus on known aberrations, in this one, cytogenetic changes were characterized and correlated with clinical and histopathologic parameters.

METHODS. Karyotypes of 74 primary uveal melanomas were analyzed with respect to the presence or absence of chromosomal gains and losses. In the analysis, classic clinical and histopathologic parameters were analyzed together with the chromosomal aberrations.

RESULTS. At a median follow-up of 43 months, 34 patients had died or had metastatic disease. Clonal chromosomal abnormalities were present in 59 tumors. The most frequent chromosomal abnormalities involved chromosome 8 (53%); loss of chromosome 3, p-arm (41%) and q-arm (42%); partial loss of chromosome 1, p-arm (24%); and abnormalities in chromosome 6 that resulted in gain of 6p (18%) and/or loss of 6q (28%). Less-frequent aberrations were abnormalities in chromosome 16, in particular loss of chromosome 16 q-arm (16%). In the univariate analysis, loss of chromosome 3, largest tumor diameter, gain in 8q, and mixed/epithelioid cell type in the tumor compared with tumors without these chromosomal changes or with a spindle cell type was associated with decreased disease-free survival. When corrected for confounding variables, significance of gain of 8q and cell type was decreased, whereas the significance of loss of chromosome 3p or 3q and largest tumor diameter remained the same.

CONCLUSIONS. Monosomy 3 and largest tumor diameter are the most significant in determining survival of patients with uveal melanoma. Abnormalities in the q-arm of chromosome 16 are relatively common in uveal melanoma, but are not associated with survival or other cytogenetic or histopathologic parameters.




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