Immunohistochemical analysis of DNA mismatch repair enzyme hMSH-2 in normal human skin and basal cell carcinomas

We have analysed the expression and distribution of the DNA mismatch repair enzyme hMSH-2 in normal skin and basal cell carcinomas. hMSH-2 protein was investigated immunohistochemically (normal human skin: n = 10; basal cell carcinomas: n = 16) on frozen sections using a highly sensitive streptavidi n-peroxidase technique and a specific mouse monoclonal antibody (clone FE11 ). In normal human skin, we found nuclear immunoreactivity for hMSH-2 in ep idermal keratinocytes of the basal and first 1-3 suprabasal cell layers. Al l basal cell carcinomas analysed revealed strong nuclear imunoreactivity th at was pronounced in peripheral tumour cells and cells of the palisade. Exp ression of hMSH-2 protein was consistently and strongly upregulated in tumo ur cells of the carcinomas as compared to adjacent unaffected epidermis or epidermis of normal human skin. Twelve of the sixteen carcinomas analysed r evealed no visual correlation in comparing the labelling patterns for hMSH- 2 with the labelling pattern for the proliferation marker Ki-67. Our findin gs indicate that (a) hMSH-2 is expressed in human epidermal keratinocytes, predominantly in lower cell layers of the viable epidermis; (b) expression of hMSH-2 protein is strongly upregulated in basal cell carcinomas as compa red to unaffected epidermis; (c) the level of hMSH-2 proteins in the carcin omas is not exclusively regulated by the proliferative activity of these tu mour cells; (d) inactivating mutations of the hMSH-2 gene may in the carcin omas not be involved in the carcinogenesis or microsatellite instability se condary to replication errors; (e) expression of hMSH-2 may be of importanc e for the genetic stability of basal cell carcinomas in vivo.