Background: The p27(KIP1) and p57(KIP2) proteins belong to the CIP/KIP family of cyclin-dependent kinase inhibitors involved in the growth arrest and cellular senescence. High levels of p27(KIP1) unexpectedly have been detected in invasive malignant melanomas (MM), whereas the role of p57(KIP2) in melanocytic lesions is unknown. We therefore chose to study the expression of p27(KIP1) and p57(KIP2) in melanocytic neoplasms.
Design: The expression of p27(KIP1) and p57(KIP2) were examined by immunohistochemistry in 40 melanocytic neoplasms and by Western blot analysis in cultured human melanocytes.
Results: Expression of both nuclear p27(KIP1) and p57(KIP2) (> 10% of cells with nuclear labeling) was observed in most cases with non-proliferating melanocytes (8/10, benign nevi and 9/10 DN, dysplastic nevi), but in only a few cases containing proliferating melanocytes (3/11 RN, recurrent nevi and 2/9 MM, melanoma) (p < 0.002). In proliferating melanocytes, there was an inverse correlation of nuclear expression of p27(KIP1) and p57(KIP2) in both RN (p27(KIP1) = 3/11 RN and p57(KIP2) = 8/11 RN) and MM (p27(KIP1) = 7/9 MM and p57(KIP2) = 2/9 MM) (p < 0.05). Western blot analysis detected p57(KIP2) only in proliferating melanocytes. p27(KIP1) was detected in both proliferating and senescent melanocytes.
Conclusion: The difference in expression patterns of p27(KIP1) and p57(KIP2) in proliferating and senescent melanocytes suggests the interplay between these proteins may play a functional role in melanocytic tumorigenesis.