Levels of cyclin D1 and D3 in malignant melanoma: Deregulated cyclin D3 expression is associated with poor clinical outcome in superficial melanoma

We examined 172 primary (110 superficial and 62 nodular) and 73 metastatic melanomas, as well as 10 benign nevi, for protein expression of cyclin D1 a nd cyclin D3 and evaluated the relationship between deregulated protein lev els and clinical outcome. For both proteins, a heterogeneous nuclear staini ng pattern was observed. Cyclin D3 was expressed by 96% of primary and 97% of metastatic melanomas, The corresponding percentages for cyclin D1 were 6 2% and 29%, respectively. In benign nevi, only rare cyclin D3-positive cell s and no cyclin D1-positive cells were observed. High levels of cyclin D3 ( >5% of the cells stained) were detected in 26 of 62 (42%) nodular melanomas and in 22 of 110 (20%) superficial tumors, whereas no such difference was observed with respect to cyclin D1, In superficial melanomas, a significant concordant staining pattern was observed between cyclin D1 and cyclin D3 ( P = 0.0009), cyclin D1 and Ki-67 (P = 0.0001), cyclin D1 and cyclin A (P = 0.02), cyclin D3 and Ki-67 (P < 0.00001), and cyclin D3 and cyclin A (P = 0 .002), Kaplan-Meier analysis revealed that high levels of cyclin D3 were an indicator of early relapse and decreased overall survival for patients wit h superficial (P = 0.001 and P = 0.009, respectively) but not nodular (P = 0.64 and P = 0.23) melanoma, Cyclin D1 did not have any impact on disease-f ree and overall survival for either of the subtypes, In conclusion, our res ults suggest that deregulation of cyclin D3 expression leading to increased proliferation may be a prognostic factor for superficial melanoma, whereas deregulated cell cycle machinery seems to have little impact on disease pr ogression of nodular melanoma.