CYCLIN KINASE INHIBITOR P21(WAF1 CLP1) IN MALIGNANT-MELANOMA - REDUCED EXPRESSION IN METASTATIC LESIONS/

Immunohistochemical analysis of the expression of the cyclin kinase in hibitor p21(WAF1/CIP1) in a panel of primary and metastatic human mela nocytic tumors was performed It was found that, independent of the p53 status, approximately 30% of the primary melanomas and 40% of the met astases completely lacked expression of this cell cycle inhibitor, Som e tumors were also analyzed by Northern blotting, and in most of the c ases a consistant cos relation between mRNA and protein expression was observed In four benign nevi studied, WAF1/CIP1 mRNA was expressed wh ereas the protein was not detected suggesting a post-transcriptional r egulation of the inhibitor in these cases. Ih superficial spreading me lanomas, a significant correlation between protein expression and tumo r thickness was found, with thin lesions showing low protein levels. I nterestingly, by comparing primary cold metastatic specimens obtained from the same patient, a reduction in p21(WAF1/CIP1) antibody staining was observed in the latter probably reflecting a more aggressive phen otype of the metastases. In conclusion, our results demonstrate the co mplexity in the relationship between p21(WAF1/CIP1) expression and tum or phenotype and furthermore suggest that aberrant expression of the c yclin-dependent kinase inhibitor may be of importance in the developme nt and progression of sporadic malignant melanoma.