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

Elisabetta Panza, Paola De Cicco, Giuseppe Ercolano, Chiara Armogida, Giosuè Scognamiglio, Anna Maria Anniciello, Gerardo Botti, Giuseppe Cirino, Angela Ianaro

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)57077-57085
Number of pages9
JournalOncotarget
Volume7
Issue number35
DOIs
Publication statusPublished - 2016

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Keywords

  • COX-2 mice
  • Cyclooxygenase-2
  • Malignant melanoma
  • Metastasis
  • Progression free survival

ASJC Scopus subject areas

  • Oncology

Cite this

Panza, E., Cicco, P. D., Ercolano, G., Armogida, C., Scognamiglio, G., Anniciello, A. M., Botti, G., Cirino, G., & Ianaro, A. (2016). Differential expression of cyclooxygenase-2 in metastatic melanoma affects progression free survival. Oncotarget, 7(35), 57077-57085. https://doi.org/10.18632/oncotarget.10976