title: Differential expression of cyclooxygenase-2 in metastatic melanoma affects progression free survival.
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-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.
authors: Department of Pharmacy, University of Naples Federico II, Naples Italy.
authors: Elisabetta
authors: E
authors: Panza
authors: Department of Pharmacy, University of Naples Federico II, Naples Italy.
authors: Paola
authors: P
authors: De Cicco
authors: Department of Pharmacy, University of Naples Federico II, Naples Italy.
authors: Giuseppe
authors: G
authors: Ercolano
authors: Department of Pharmacy, University of Naples Federico II, Naples Italy.
authors: Chiara
authors: C
authors: Armogida
authors: Department of Experimental Oncology, National Cancer Institute, G. Pascale, Naples, Italy.
authors: Giosuè
authors: G
authors: Scognamiglio
authors: Department of Experimental Oncology, National Cancer Institute, G. Pascale, Naples, Italy.
authors: Anna Maria
authors: AM
authors: Anniciello
authors: Department of Experimental Oncology, National Cancer Institute, G. Pascale, Naples, Italy.
authors: Gerardo
authors: G
authors: Botti
authors: Department of Pharmacy, University of Naples Federico II, Naples Italy.
authors: Giuseppe
authors: G
authors: Cirino
authors: Department of Pharmacy, University of Naples Federico II, Naples Italy.
authors: Angela
authors: A
authors: Ianaro
mesh_terms: D000328:Adult; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000378:metabolism*; D008546:Melanoma, Experimental; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism*; D046888:Tissue Array Analysis; D016896:Treatment Outcome
chemical_list: D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human
keywords: COX-2-/- mice; cyclooxygenase-2; malignant melanoma; metastasis; progression free survival