Decreased expression of MLH1, MSH2, PMS1 and PMS2 in pigmented lesions indicates accumulation of failed DNA repair along with malignant transformation and tumour progression.

The tumorigenesis of human nonpolyposis colorectal cancer was reported to be connected with the mutations in DNA mismatch repair genes. The main aim of this study was to check the epression of 4 proteins MLH1, MSH2, PMS1 and PMS2 responsible for mismatch DNA repair in naevi and melanomas. Fifty-one naevi, 78 primary melanomas, 30 lymphatic and 7 organ melanoma metastases were stained for the presence of MLH1, MSH2, PMS1 and PMS2. All proteins were preserved in 88% of naevi and only in 37% of primary melanomas, 17% of lymphatic metastases and in none of the distant metastases. The difference of expression of all 4 proteins between naevi and melanomas was highly significant (p<0.01). MLH1 and MSH2 correlated significantly with each other as well with the follow-up of patients. On the basis of our results one can conclude that the defect of mismatch DNA repair plays an important role in both tumorigenesis of melanoma and metastatic spread of tumour.