Alterations of mismatch repair protein expression in benign melanocytic nevi, melanocytic dysplastic nevi, and cutaneous malignant melanomas

Immunoperoxidase-staining methods were used to examine the expression of hM LH1, hMSH2, and hMSH6 mismatch repair (MMR) proteins in 50 melanocytic lesi ons. Microsatellite instability (MSI), screened previously in these lesions by polymerase chain reaction-based microsatellite assay, showed low-level microsatellite instability (MSI-L) in 11 of 22 melanocytic dysplasfic nevi (MDN) and two of nine primary cutaneous malignant melanomas (CMMs) but not in the benign melanocytic nevi (BN). Mismatch repair proteins were widely e xpressed in the epidermis and adnexal structures. All lesions showed positi ve immunoreactivity with a gradual decrease in the MMR staining values duri ng the progression from BN to MDN to CMMs, The average percentage of positi vely (PP) stained cells for hMLH1, hMSH2, and hMSH6 in BN was 85.50 +/-1.95 , 77.90 +/-4.50, and 87.11 +/-1.85, respectively. The PP cell values in CMM s were significantly reduced as compared with BN (75.22 +/-3.57, p = 0.01; 56.11 +/-8.73, p = 0.02; 6522 +/-6.47, p = 0.0002 for hMLH1, hMSH2, and hMS H6, respectively). No comparable significant difference was found between m icrosatellite stable and MSI-L lesions (p = 0.173 p = 0.458, and p = 0.385) , suggesting a lack of correlation between MMR. expression and MMR function . There was a direct correlation between PP cell values of hMSH2 and hMSH6 (R = 0.39, p = 0.008), implying that their expression could be regulated by a common mechanism. Thus, an important finding Of these studies was the re duction of MMR protein levels in CMMs; whether this reflects underlying gen etic or epigenetic mechanisms is still to be determined.