Microsatellite instability and alterations of mismatch repair protein expression in choroidal melanomas.
OBJECTIVE
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.


CONCLUSIONS
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.
Hussein
Mahmoud R
MR
Department of Pathology, Faculty of Medicine, Assuit University, Assuit University Hospitals, Assuit, Egypt.
Haemel
Anna K
AK
Albert
Daniel M
DM
Wood
Gary S
GS
D020137:Base Pair Mismatch / Q000235:genetics; D002830:Choroid Neoplasms / Q000235:genetics* / Q000378:metabolism; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D042822:Genomic Instability; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D051718:MutS Homolog 2 Protein / Q000235:genetics* / Q000378:metabolism; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D004273:DNA, Neoplasm; D011506:Proteins; C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein