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The possible correlation between cyclooxygenase-2 (COX-2) expression and disease progression in melanoma is still a matter of debate. Analysis of COX-2 expression in 45 lymph node melanoma metastases demonstrates a significant correlation between the percent of expression and progression free survival (PFS). A positive COX-2 expression≥ 10%(COX-2 high), as opposite to a positive expression≤ 9%(COX-2 low), translated into a striking significant reduction of PFS of about 3 years. The reduction in PFS correlated neither with BRAF V600E nor with NRAS Q61 expression in the analyzed samples. This concept was reinforced by the finding that tumour development in COX-2−/− mice was almost blunted. Similarly, inhibition of COX-2 protein expression in human melanoma cell lines, by using siRNAs technology as well as selective inhibition of COX-2 activity by celecoxib, reduced cellular proliferation and …