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[Cancer Research 62, 632-635, February 1, 2002]
© 2002 American Association for Cancer Research

Advances in Brief

Prognostic Significance of Elevated Cyclooxygenase-2 Expression in Breast Cancer1

Ari Ristimäki2,3, Anna Sivula2, Johan Lundin, Mikael Lundin, Tiina Salminen, Caj Haglund, Heikki Joensuu and Jorma Isola

Departments of Pathology [A. R., A. S.], Oncology [J. L., M. L., T. S., H. J., J. I.], and Surgery [C. H.], Helsinki University Central Hospital, FIN-00014 Helsinki, Finland; Molecular and Cancer Biology Research Program, Biomedicum Helsinki University, FIN-00014 Helsinki, Finland [A. R., A. S., H. J.]; and Institute of Medical Technology, University of Tampere and Tampere University Hospital, FIN-33014 Tampere, Finland [J. I.]

Cyclooxygenase-2 (Cox-2) expression can induce mammary tumorigenesis in transgenic mice, and selective Cox-2 inhibitors are both chemopreventive and chemotherapeutic in rat models of breast cancer. We analyzed the expression of Cox-2 protein by immunohistochemistry in tissue array specimens of 1576 invasive breast cancers. Moderate to strong (elevated) expression of Cox-2 protein was observed in 37.4% of the tumors, and it was associated with unfavorable distant disease-free survival (P < 0.0001). Elevated Cox-2 expression was associated with a large tumor size, a high histological grade, a negative hormone receptor status, a high proliferation rate (identified by Ki-67), high p53 expression, and the presence of HER-2 oncogene amplification (P < 0.0001 for all comparisons), along with axillary node metastases and a ductal type of histology (P = 0.0001 and P = 0.0017, respectively). Interestingly, association with the unfavorable outcome was especially apparent in the subgroups defined by estrogen receptor positivity, low p53 expression, and no HER-2 amplification (P < 0.0001 for all comparisons). These results indicate that elevated Cox-2 expression is more common in breast cancers with poor prognostic characteristics and is associated with an unfavorable outcome. The present findings support efforts to initiate clinical trials on the efficacy of Cox-2 inhibitors in adjuvant treatment of breast cancer.




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