Cyclin kinase inhibitor p21WAF1/CIP1 in malignant melanoma: reduced expression in metastatic lesions.
Immunohistochemical analysis of the expression of the cyclin kinase inhibitor p21WAF1/CIP1 in a panel of primary and metastatic human melanocytic tumors was performed. It was found that, independent of the p53 status, approximately 30% of the primary melanomas and 40% of the metastases completely lacked expression of this cell cycle inhibitor. Some tumors were also analyzed by Northern blotting, and in most of the cases a consistant correlation between mRNA and protein expression was observed. In four benign nevi studied, WAF1/CIP1 mRNA was expressed whereas the protein was not detected, suggesting a post-transcriptional regulation of the inhibitor in these cases. In superficial spreading melanomas, a significant correlation between protein expression and tumor thickness was found, with thin lesions showing low protein levels. Interestingly, by comparing primary and metastatic specimens obtained from the same patient, a reduction in p21WAF1/CIP1 antibody staining was observed in the latter, probably reflecting a more aggressive phenotype of the metastases. In conclusion, our results demonstrate the complexity in the relationship between p21WAF1/CIP1 expression and tumor phenotype and furthermore suggest that aberrant expression of the cyclin-dependent kinase inhibitor may be of importance in the development and progression of sporadic malignant melanoma.
Maelandsmo
G M
GM
Department of Tumor Biology, Norwegian Radium Hospital, Oslo, Norway.
Holm
R
R
Fodstad
O
O
Kerbel
R S
RS
Flørenes
V A
VA
D014408:Biomarkers, Tumor / Q000032:analysis*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008545:Melanoma / Q000737:chemistry / Q000201:enzymology* / Q000556:secondary*; D012878:Skin Neoplasms / Q000737:chemistry* / Q000201:enzymology* / Q000473:pathology; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D014408:Biomarkers, Tumor; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D016159:Tumor Suppressor Protein p53