Different expression patterns of p27^KIP1 and p57^KIP2 proteins in benign and malignant melanocytic neoplasms and in cultured human melanocytes

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.