Relationship between the expression of cyclooxygenase 2 and MDR1/P-glycoprotein in invasive breast cancers and their prognostic significance

Abstract

Introduction: Recent reports suggest that expression of the cyclooxygenase 2 (COX-2) enzyme may up-regulate expression of MDR1/P-glycoprotein (MDR1/P-gp), an exponent of resistance to cytostatic drugs. The present study aimed at examining the relationship between the expression of COX-2 and of MDR1/P-gp in a group of breast cancer cases. Methods: Immunohistochemical reactions were performed using monoclonal antibodies against COX-2 and MDR1/P-gp on samples originating from 104 cases of primary invasive breast cancer. Results: COX-2-positive cases were shown to demonstrate higher expression of MDR1/P-gp (P < 0.0001). The studies also demonstrate that COX-2 expression was typical for cases of a higher grade (P = 0.01), a shorter overall survival time (P < 0.0001) and a shorter progression-free time (P < 0.0001). In the case of MDR1/P-gp, its higher expression characterised cases of a higher grade (P < 0001), with lymph node involvement (P < 0001), and shorter overall survival (P < 0.0001) and progression-free time (P < 0.0001). Conclusion: Our studies confirmed the unfavourable prognostic significance of COX-2 and MDR1/P-gp. We also document a relationship between COX-2 and MDR1/P-gp, which suggests that COX-2 inhibitors should be investigated in trials as a treatment supplementary to chemotherapy of breast cancers.