Assessment of genetic instability in melanocytic skin lesions through microsatellite analysis of benign nevi, dysplastic nevi, primary melano-mas along with their metastases.

Microsatellite instability (MSI) is caused by replication errors due to deficient DNA mismatch repair and has been associated with tumour progression in different types of cancer. Controversial results have been provided about both frequency and significance of MSI in malignant melanoma (MM). In this study, time of onset and relative incidence of MSI were determined during the progression of melanocytic tumours, starting from benign melanocytic nevi. MSI was studied at 13 loci containing single-, di-, or trinucleotide repeat sequences and mapping to five different chromosomal locations. Tumours were classified as low-frequency (L-MSI+) or high-frequency (H-MSI+) MSI, when one or at least two marker loci (respectively) displayed mutant alleles in tumour DNA compared to corresponding normal tissue DNA. None of the 8 melanocytic nevi showed MSI, whereas moderate frequency of H-MSI was detected in dysplastic nevi (1/11; 9%) and primary melanomas (6/56; 11%). The incidence of MSI was increased in melanoma metastases from the same patients (H-MSI: 9/42; 21%). In contrast to previously reported data showing higher rates of MSI in melanoma, genetic instability seems to be present in a minority of MM lesions. However, our findings are consistent with the hypothesis that MSI may be sequentially induced during malignant evolution, contributing to the progression of a subset of melanocytic tumours.