Journal
ONCOTARGET
Volume 7, Issue 35, Pages 57077-57085Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.10976
Keywords
malignant melanoma; cyclooxygenase-2; COX-2(-/-) mice; progression free survival; metastasis
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Funding
- Italian Government (PRIN) [2012WBSSY4_005]
- Italian Government (FIRB) [RBFR126IGO_002]
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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 invasiveness. In conclusion we show that COX-2(high) is a negative prognostic factor in metastatic melanoma. Our study also clarifies that the uncertainty about the role of COX-2 in metastatic malignant melanoma, found in the current relevant literature, is probably due to the fact that a threshold in COX-2 expression has to be reached in order to impact on cancer malignancy. Our findings suggest that COX-2 expression may become an useful diagnostic tool in defining melanoma malignancy as well as argue for a possible therapeutic use of NSAID as add on therapy in selected cases.
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