Cyclooxygenase-2 expression in advanced nasopharyngeal carcinoma-a prognostic evaluation and correlation with hypoxia inducible factor 1α and vascular endothelial growth factor

Cycloxygenase-2 (COX-2), hypoxia inducible factor 1-α (HIF-1α) and vascular endothelial growth factor (VEGF) can be induced by the Epstein-Barr virus oncoprotein latent membrane protein-1 (LMP-1) in nasopharyngeal cancer (NPC) cell lines. This study examined the prognostic relevance of COX-2 and its relationship with HIF-1α and VEGF expression in NPC biopsies. Primary tumor biopsies were obtained from 78 participants of a randomized trial who received radiotherapy (RT) with or without concurrent chemotherapy for locoregionally advanced NPC. These were analyzed for COX-2 expression and then correlated with age, sex, disease stage, treatment arm, survival and disease recurrence, VEGF and HIF-1α expression in a regression model. 83% of tumors expressed COX-2, 47% co-expressed COX-2 and VEGF, 38% co-expressed COX-2 and HIF-1α. On univariate analysis, COX-2 expression did not correlate with survival and recurrence, but moderate to high COX-2 expression was associated with advanced nodal stage (p = 0.03). Although univariate analysis showed that COX-2-HIF-1α co-expression was associated with worse progression-free survival (p = 0.046), time to local (p = 0.004) and regional recurrence (p = 0.007), multivariate analysis failed to confirm any correlation between COX-2-HIF-1α or COX-2-VEGF co-expression and survival or disease recurrence. Contrary to previous report, this study failed to demonstrate any prognostic significance of COX-2 expression alone or co-expression with HIF-1α or VEGF in advanced NPC.