Purpose: Circumstantial evidence suggests that development of uveal melanoma may be associated to two different pathogenetic pathways, either loss of chromosome 3 or extra copies of 6p (+6p). Chromosome 3 monosomy (-3) is detected in approximately half of uveal melanomas, and is strongly linked to metastatic disease, whereas +6p accounts for one-fourth of uveal melanomas with no clear clinical correlations. The aim of our study was to verify if the analysis of chromosomes 3 and 6 was able to distinguish two groups of patients for translating this approach in the clinical practise as prognostic tool.
Methods: Fluorescence in situ hybridisation (FISH) with probes for chromosome 3, 6p and 6q was used to analyze cytological material obtained by fine needle aspiration biopsy (FNAB) from 28 primary uveal melanomas, just before brachytherapy.
Results: Abnormalities affecting 6p and 6q were found in 14 tumors (50%), and -3 in 16 cases (57%). Interestingly, -3 and +6p were mutually exclusive in 23 cases (82%), whereas in two cases only (7%) they coexisted. In particular, +6p alone was present in 9 lesions (32%), -3 was the sole aberration in 11 cases (39%), and concomitant -3 and -6q in 3 other cases (11%).
Conclusions: Although the patient cohort is limited, our findings confirm the hypothesis of a bifurcated pathogenetic model of uveal melanoma. Moreover, our results suggest that investigation of both markers on FNAB samples obtained in vivo could provide a clearer clinical picture of genetic lesions when no histological material is available for prognostic evaluation.