Abstract 729: Prognostic significance of COX-2 over-expression in BRAF mutated Middle Eastern PTC

Abstract

Abstract The cyclooxygenase-2 (COX-2) - prostaglandin E2 (PGE2) pathway has been implicated in carcinogenesis with BRAF mutation shown to promote PGE2 synthesis. This study was conducted to evaluate COX-2 expression in a large cohort of Middle Eastern Papillary Thyroid Carcinoma (PTC) and further evaluate the prognostic significance of COX-2 expression in strata of BRAF mutation status. BRAF mutation analysis was performed by Sanger sequencing and COX-2 expression was evaluated immunohistochemically using tissue microarray. COX-2 over-expression was noted in 43.2% (567/1314) of cases and was significantly associated with poor prognostic markers such as extra-thyroidal extension, lymph node metastasis and higher tumor stage. COX-2 was also an independent predictor of poor disease-free survival (DFS). Most notably, the association of COX-2 expression with DFS differed by BRAF mutation status. COX-2 over-expression was associated with poor DFS in BRAF mutant but not BRAF wild-type PTCs with the multivariate-adjusted hazard ratio of 2.10 (95% CI = 1.52 - 2.92; p < 0.0001) for COX-2 over-expressed tumors in BRAF mutant PTC. In conclusion, the current study shows that COX-2 plays a key role in prognosis of PTC patients. Furthermore, a significant association of COX-2 expression with poor DFS was noted in BRAF mutated tumors. Our data suggests the potential therapeutic role of COX-2 inhibition in patients with BRAF mutated PTC. Citation Format: Rong Bu, Sandeep K. Parvathareddy, Abdul K. Siraj, Padmanaban Annaiyappanaidu, Kaleem Iqbal, Maha Al Rasheed, Wael Haqawi, Khawla S. Al-Kuraya. Prognostic significance of COX-2 over-expression in BRAF mutated Middle Eastern PTC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 729.