Differential expression of cyclooxygenase-2 in metastatic melanoma affects progression free survival
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Elisabetta Panza1,*, Paola De Cicco1,*, Giuseppe Ercolano1, Chiara Armogida1, Giosuè Scognamiglio2, Anna Maria Anniciello2, Gerardo Botti2, Giuseppe Cirino1, Angela Ianaro1
1Department of Pharmacy, University of Naples Federico II, Naples Italy
2Department of Experimental Oncology, National Cancer Institute, G. Pascale, Naples, Italy
*These authors have contributed equally to this work
Giuseppe Cirino, email: email@example.com
Keywords: malignant melanoma, cyclooxygenase-2, COX-2-/- mice, progression free survival, metastasis
Received: April 11, 2016 Accepted: July 19, 2016 Published: August 01, 2016
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-2high), as opposite to a positive expression ≤9% (COX-2low), translated into a striking significant reduction of PFS of about 3 years. The reduction in PFS correlated neither with BRAFV600E nor with NRASQ61 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-2high 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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