Levels of Cyclin D1 and D3 in Malignant Melanoma: Deregulated Cyclin D3 Expression Is Associated with Poor Clinical Outcome in Superficial Melanoma
2000
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 and cyclin D3 and evaluated the relationship between deregulated
protein levels and clinical outcome. For both proteins, a heterogeneous
nuclear staining pattern was observed. Cyclin D3 was expressed by 96%
of primary and 97% of metastatic melanomas. The corresponding
percentages for cyclin D1 were 62% and 29%, respectively. In benign
nevi, only rare cyclin D3-positive cells 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 with 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-free and overall survival for either of the subtypes.
In conclusion, our results 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 progression of nodular
melanoma.
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