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Advances in Brief |
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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M. L. Gauthier, C. R. Pickering, C. J. Miller, C. A. Fordyce, K. L. Chew, H. K. Berman, and T. D. Tlsty p38 Regulates Cyclooxygenase-2 in Human Mammary Epithelial Cells and Is Activated in Premalignant Tissue Cancer Res., March 1, 2005; 65(5): 1792 - 1799. [Abstract] [Full Text] [PDF] |
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X.-H. Liu, A. Kirschenbaum, K. Yu, S. Yao, and A. C. Levine Cyclooxygenase-2 Suppresses Hypoxia-induced Apoptosis via a Combination of Direct and Indirect Inhibition of p53 Activity in a Human Prostate Cancer Cell Line J. Biol. Chem., February 4, 2005; 280(5): 3817 - 3823. [Abstract] [Full Text] [PDF] |
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K. Muller-Decker, I. Berger, K. Ackermann, V. Ehemann, S. Zoubova, S. Aulmann, W. Pyerin, and G. Furstenberger Cystic Duct Dilatations and Proliferative Epithelial Lesions in Mouse Mammary Glands upon Keratin 5 Promoter-Driven Overexpression of Cyclooxygenase-2 Am. J. Pathol., February 1, 2005; 166(2): 575 - 584. [Abstract] [Full Text] [PDF] |
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J. Zhou, T. Suzuki, A. Kovacic, R. Saito, Y. Miki, T. Ishida, T. Moriya, E. R. Simpson, H. Sasano, and C. D. Clyne Interactions between Prostaglandin E2, Liver Receptor Homologue-1, and Aromatase in Breast Cancer Cancer Res., January 15, 2005; 65(2): 657 - 663. [Abstract] [Full Text] [PDF] |
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A. J. Dannenberg, S. M. Lippman, J. R. Mann, K. Subbaramaiah, and R. N. DuBois Cyclooxygenase-2 and Epidermal Growth Factor Receptor: Pharmacologic Targets for Chemoprevention J. Clin. Oncol., January 10, 2005; 23(2): 254 - 266. [Abstract] [Full Text] [PDF] |
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M Lacroix, R-A Toillon, and G Leclercq Stable 'portrait' of breast tumors during progression: data from biology, pathology and genetics Endocr. Relat. Cancer, September 1, 2004; 11(3): 497 - 522. [Abstract] [Full Text] [PDF] |
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G. Ferrandina, F. O. Ranelletti, F. Legge, M. Gessi, V. Salutari, M. G. Distefano, L. Lauriola, G. F. Zannoni, E. Martinelli, and G. Scambia Prognostic Role of the Ratio between Cyclooxygenase-2 in Tumor and Stroma Compartments in Cervical Cancer Clin. Cancer Res., May 1, 2004; 10(9): 3117 - 3123. [Abstract] [Full Text] [PDF] |
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N Nathoo, G H Barnett, and M Golubic The eicosanoid cascade: possible role in gliomas and meningiomas J. Clin. Pathol., January 1, 2004; 57(1): 6 - 13. [Abstract] [Full Text] [PDF] |
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