Prognostic Significance of COX-2 Overexpression in BRAF -Mutated Middle Eastern Papillary Thyroid Carcinoma

• Published in: International journal of molecular sciences Vol. 21; no. 24; p. 9498
• Main Authors: Parvathareddy, Sandeep Kumar, Siraj, Abdul K, Annaiyappanaidu, Padmanaban, Al-Sobhi, Saif S, Al-Dayel, Fouad, Al-Kuraya, Khawla S
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 14-12-2020; MDPI
• Subjects: Adult; Biomarkers; BRAF mutation; Carcinogenesis; Carcinogens; Cyclooxygenase 2 - genetics; Cyclooxygenase 2 - metabolism; Cyclooxygenase-2; Deoxyribonucleic acid; Disease-Free Survival; DNA; Female; Humans; Immunohistochemistry; Inflammation; Kinases; Male; Medical prognosis; Metastases; Metastasis; Middle Aged; Multivariate Analysis; Mutants; Mutation; Mutation - genetics; Papillary thyroid carcinoma; Patients; Prognosis; Proportional Hazards Models; Prostaglandin E2; Proto-Oncogene Proteins B-raf - genetics; Thyroid; Thyroid cancer; Thyroid Cancer, Papillary - enzymology; Thyroid Cancer, Papillary - genetics; Thyroid Cancer, Papillary - pathology; Thyroid Neoplasms - enzymology; Thyroid Neoplasms - genetics; Thyroid Neoplasms - pathology; Tumors; Saudi Arabia; United States > US; disease-free survival; papillary thyroid carcinoma; cyclooxygenase-2; BRAF mutation
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21249498

The cyclooxygenase-2 (COX-2)-prostaglandin E2 (PGE2) pathway has been implicated in carcinogenesis, with
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
mutation status.
mutation analysis was performed using Sanger sequencing, and COX-2 expression was evaluated immunohistochemically using tissue microarray (TMA). COX-2 overexpression, noted in 43.2% (567/1314) of cases, 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
mutation status. COX-2 overexpression was associated with poor DFS in
-mutant but not
wild-type PTCs, with a multivariate-adjusted hazard ratio of 2.10 (95% CI = 1.52-2.92;
< 0.0001) for COX-2 overexpressed tumors in
-mutant PTC. In conclusion, the current study shows that COX-2 plays a key role in prognosis of PTC patients, especially in
mutated tumors. Our data suggest the potential therapeutic role of COX-2 inhibition in patients with
-mutated PTC.