IMMUNOHISTOCHEMICAL DETECTION OF P53 IN MELANOMAS WITH RARE P53 GENE-MUTATIONS IS ASSOCIATED WITH MDM-2 OVEREXPRESSION

Expression of mutant p53 detected by immunohistochemistry has been des cribed in human malignant melanoma, but there are few reports of molec ular analyses. To investigate the genetic basis for p53 expression in malignant melanoma, we examined 58 primary tumors and 5 cutaneous meta stases. The entire coding sequence of the p53 gene was screened by sin gle-strand conformation polymorphism analysis and direct genomic seque ncing of polymerase chain reaction products. p53 and mdm-2 expression were studied by immunohistochemistry. Two p53 gene mutations could be found in 1/63 samples examined, both having occurred in the same speci men from a patient with a nodular melanoma p53 and mdm-2 expression we re found immunohistochemically to increase with tumor progression both in frequency and in the mean proportion of positive cells, with the s ame cases staining positively for both antibodies. Our results suggest that a) p53 gene mutations are a rare event in human melanoma; b) acc umulation and thus immunohistochemically detectable expression of p53 may result from posttranslational mechanisms affecting the p53 gene pr oduct; and c) p53 and mdm-2 are more important in late events in melan oma carcinogenesis.