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

Breast Cancer Res. 2005;7(5):R862-70. doi: 10.1186/bcr1313. Epub 2005 Aug 25.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / enzymology
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology*
  • Cyclooxygenase 2 / metabolism*
  • Disease Progression
  • Female
  • Humans
  • Immunohistochemistry
  • Prognosis
  • Survival Analysis
  • Time Factors

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Cyclooxygenase 2