Assessment of genetic instability in melanocytic skin lesions through microsatellite analysis of benign naevi, dysplastic naevi, and primary melanomas and their metastases.

Microsatellite instability (MSI) is caused by replication errors due to deficient DNA mismatch repair and has been associated with tumour progression in various types of cancer. Controversial results have been reported concerning the frequency and significance of MSI in malignant melanoma. In this study, the time of onset and relative incidence of MSI were determined during the progression of melanocytic tumours, starting with benign melanocytic naevi. MSI was studied at 13 loci containing single, di- or trinucleotide repeat sequences and mapping to five different chromosomal locations. Tumours were classified as being low frequency MSI (L-MSI+) or high frequency MSI (H-MSI+) when either one or at least two marker loci, respectively, displayed mutant alleles in tumour DNA compared with the corresponding normal tissue DNA. None of the eight melanocytic naevi studied showed MSI, whereas a moderate frequency of H-MSI was detected in dysplastic naevi (one out of 11; 9%) and primary melanomas (six out of 56; 11%). The incidence of H-MSI was increased in melanoma metastases from the same patients (nine out of 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 malignant melanoma 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.