Microsatellite instability (NISI) is caused by deficient DNA mismatch: repa
ir, and results in a "mutator" phenotype. Recent studies have produced cont
radictory results about the frequency and significance of MSI in malignant
melanomas. In this study, we therefore determined the time of onset and rel
ative frequency of MSI during the progression of melanocytic tumours, inclu
ding benign melanocytic naevi. We examined 7 different microsatellite loci
in 9 melanocytic nae-vi, 25 primary malignant melanomas and 8 melanoma meta
stases. None of the melanocytic naevi showed MSI. In contrast, moderate fre
quency of NISI in 1/12 (8%) was detected in thin melanomas of <0.75mm verti
cal thickness and in 1/8 (12%) of those with a thickness >0.75 non and <1.5
mm. The rate of NISI was increased in tumours thicker than 1.5 mm (2/5) an
d in melanoma metastases, with over 25% (2/8) of the lesions investigated.
We conclude that NISI occurs in a considerable subset of malignant melanoma
s and that there is a pattern consistent with increasing frequency of NISI
with progression of melanocytic tumours.