Differential expression of cyclooxygenase-2 in metastatic melanoma affects progression free survival

// Elisabetta Panza 1, * , Paola De Cicco 1, * , Giuseppe Ercolano 1 , Chiara Armogida 1 , Giosue Scognamiglio 2 , Anna Maria Anniciello 2 , Gerardo Botti 2 , Giuseppe Cirino 1 , Angela Ianaro 1 1 Department of Pharmacy, University of Naples Federico II, Naples Italy 2 Department of Experimental Oncology, National Cancer Institute, G. Pascale, Naples, Italy * These authors have contributed equally to this work Correspondence to: Giuseppe Cirino, email: cirino@unina.it Keywords: malignant melanoma, cyclooxygenase-2, COX-2 -/- mice, progression free survival, metastasis Received: April 11, 2016     Accepted: July 19, 2016     Published: August 01, 2016 ABSTRACT 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.