COX-2 expression in human uveal melanoma: Implication for prognosis

Purpose: Cyclooxygenase, the enzyme which catalyses the rate limiting step in the formation of prostaglandins, exists as two isoforms, COX–1 and COX–2. COX–1 is constitutively expressed in many tissues, whereas COX–2 is termed the inducible isoform and is overexpressed in inflammatory and neoplastic disease states. Prostaglandins derived from COX–2 are believed to mediate many of the proliferative, invasive and metastatic properties of tumour cells, and selective inhibitors of COX–2 attenuate metastasis in many pre–clinical models. The aim of this study was to examine the expression of COX–2 and its prognostic value in uveal melanoma. Methods: Paraffin–embedded sections from 17 clinicopathologically well–characterised cases of primary uveal melanoma were immunohistochemically stained for COX–2. In 10 cases metastatic disease led to death, and the mean follow–up of non–metastasised patients was 10 years. The expression of COX–2 was analysed with respect to both intensity and the percentage of cells stained, by 3 independent observers masked to the follow–up of patients. A COX–2 score incorporating both the intensity and % of cells stained was calculated for each sample. Statistical analyses included Kaplan–Meier survival curves, Log–Rank test, Fischers Exact test and Spearmans rank correlation coefficient. Results: Of the 17 specimens analysed 15 (88.2%) contained moderate or intense positive immunoreactivity for COX–2, and significant variation in the percentage of cells stained was observed between samples. Kaplan–Meier analysis showed a statistically significant association (P = 0.04) between COX–2 expression (COX–2 score) and metastatic death. Conclusions: Upregulation of COX–2 expression appears to be associated with poor prognosis in uveal melanoma. Further studies, extended on a larger sample of specimens, are warranted to investigate the molecular mechanism of COX–2 in uveal melanoma. Selective COX–2 inhibitors, currently in widespread clinical use for other diseases, may represent a realistic adjuvant therapy for uveal melanoma.