Objectives: To examine choroidal melanomas for genomic instability, manifested by microsatellite instability (MSI) and mismatch repair (MMR) protein alterations, and to determine the association of these alterations with selected clinicopathological features of the tumors. Methods: Polymerase chain reaction-based microsatellite assays were applied to analyze 57 cases of choroidal melanomas using 11 microsatellite markers at 5 chromosomal regions: 1p, 2p, 4q, 9p, and 17p. Immunoperoxidase staining methods and mouse monoclonal antibodies were used to investigate the expression patterns of MMR proteins. Results: Microsatellite instability was found at the 1p, 9p, and 17p regions in these lesions with an overall prevalence of 35% (20/57). The frequency of MSI ranged from 9% (1/11) to 27% (3/11), ie, low-level MSI (MSI-L). The instability was most commonly found at the 1p region (D1S2734, 55%; D1S2832, 40%; and D1S233, 20%). Two MSI banding patterns, band shifts and the appearance of additional bands, were found in 10% and 90% of the unstable lesions, respectively. The average percentages of hMLH1 and hMSH2 positively stained cells were insignificantly reduced in the unstable lesions (81.7±9.3 and 76.7±16.7) as compared with the stable lesions (84.1±15.5 and 78.6±19.6; P=.62 and 0.74 for hMLH1 and hMSH2, respectively). There was no significant difference in survival between the 2 groups; however, relative to the stable subset, the unstable tumors showed a trend (P<.10) toward occurring at a younger age and having tumor cells in vascular lakes. Conclusions: The presence of MSI-L in some choroidal melanomas defines a novel genetic subset of these tumors and suggests that MSI (genomic instability) may play a role in their molecular pathogenesis. Elucidation of the underlying mechanisms for MSI will require further investigation. Clinical Relevance: Detection of the MSI-L pattern might prove to be useful as an adjunct to the conventional diagnosis of choroidal melanomas. Larger series are needed to determine whether any of the correlative trends noted in this study will achieve statistical significance. To the best of our knowledge, this study is the first to define both the MSI and MMR protein expression features of choroidal melanomas.
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