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COX-2 Expression in Breast Cancer and Impact on Survival Outcomes

Author(s): Daniely Regina Freitas-Alves, Juliana Batoca Pinto, Fabiana Resende Rodrigues, Priscila Valverde, Danielle Clemente da Silva Fernandes, Maria Thereza Accioly, Samuel dos Santos Valenca, Jamila Ales

Purpose: The inducible inflammatory enzyme cyclooxygenase-2 (COX-2) favors carcinogenesis, but its expression in breast tumors presents great variability, with controversial prognostic impact. Here, we characterize COX-2 protein levels in breast tumors by immunohistochemistry according to gene polymorphisms, and evaluate if tumor COX-2 protein levels or mRNA are associated with survival outcomes.

Methods: First, COX-2 protein levels were quantified by immunohistochemistry in selected tissue specimens (N=236) of excised breasts from a hospital-based cohort of breast cancer in Brazil, and evaluated for their association with gene polymorphisms and histopathological variables, as well as with survival outcomes. Secondly, an online gene array database compiling information from different breast cancer cohorts was used to analyze the association between tumor COX-2 mRNA and survival outcomes.

Results: High COX-2 protein levels were associated with high tumor grade (OR=1.86; 95% CI=1.1-3.17), but not with gene variants or survival outcomes. In contrast, high COX-2 mRNA was associated with better disease-free survival when considering all cases (HR=0.82; 95%CI=0.72-0.92; N=3951) or only ER+ tumors (HR=0.62; 95%CI=0.49-0.79; N=2061), but with worse disease-free survival (HR=1.6; 95%CI=1.22-2.11; N=618) among patients with basal-like tumors.

Conclusion: Gene polymorphisms do not account for the variability on COX-2 protein levels in breast tumors, and COX-2 mRNA seems to be a better candidate for prognostic evaluation of breast cancer survival, but its impact depends on breast cancer subtypes.

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