Cyclin kinase inhibitor p21WAF1/CIP1 in malignant melanoma: reduced expression in metastatic lesions.

Abstract

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.

• Authors: G M Maelandsmo, R Holm, O Fodstad, R S Kerbel, V A Flørenes
• Journal: The American journal of pathology (Am J Pathol) Vol. 149 Issue 6 Pg. 1813-22 (Dec 1996) ISSN: 0002-9440 [Print] United States
• PMID: 8952518 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Biomarkers, Tumor
• CDKN1A protein, human
• Cyclin-Dependent Kinase Inhibitor p21
• Cyclins
• Enzyme Inhibitors
• Tumor Suppressor Protein p53

Topics

• Biomarkers, Tumor (analysis)
• Cyclin-Dependent Kinase Inhibitor p21
• Cyclins (antagonists & inhibitors)
• Enzyme Inhibitors (metabolism)
• Humans
• Immunohistochemistry
• Melanoma (chemistry, enzymology, secondary)
• Skin Neoplasms (chemistry, enzymology, pathology)
• Tumor Cells, Cultured
• Tumor Suppressor Protein p53 (analysis)