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Association of cyclooxygenase-2 and matrix metalloproteinase-2 expression in human breast cancer

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Summary

Expression of cyclooxygenase-2 (COX-2) and matrix metalloproteinase-2 (MMP-2) associates with reduced survival in human breast cancer. COX-2 may be directly involved with mammary carcinogenesis, since expression of COX-2 is sufficient for formation of breast tumors in transgenic mice, and COX-2 selective inhibitors can suppress tumorigenesis in rodent models of breast cancer. MMP-2 is an extracellular matrix degrading proteolytic enzyme that bas been linked to invasion and metastasis. A direct link between COX-2 and MMP-2 may exist, since inhibition of COX-2 activity can result in reduction of MMP-2 expression and activity. In this study we analyzed protein expression of COX-2 and MMP-2 in tissue array specimens of 278 invasive breast cancers by immunohistochemistry. Immunopositivity of these two markers was correlated with each other and with various clinicopathological parameters including survival. We found high COX-2 expression in 30% and high MMP-2 expression in 83% of the breast cancer specimens, and there was a positive association between the expression of these two factors (p=0.003). It was especially evident that whenever COX-2 expression was high, MMP-2 expression was almost invariably high (95%). Furthermore, high expression of either COX-2 or MMP-2 associated with decreased disease specific survival when compared with the COX-2 or MPP-2 low group (p=0.026 and p=0.021, respectively). Taken together, our results indicate that expression of COX-2 protein is associated with expression of MMP-2 protein in human breast cancer and that both COX-2 and MMP-2 are markers of poor prognosis in breast cancer.

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Authors and Affiliations

  1. Department of Pathology, Helsinki University Central Hospital, Helsinki

    Anna Sivula, Caj Haglund & Ari Ristimäki

  2. Molecular and Cancer Biology Research Program, Biomedicum Helsinki, University of Helsinki, Room B512b (Haartmaninkatu 8), P.O. Box 63, FIN-00014, Helsinki, Finland

    Anna Sivula, Heikki Joensuu & Ari Ristimäki

  3. Department of Oncology and Radiotherapy, University of Oulu and Oulu University Hospital, Oulu

    Anne Talvensaari-Mattila & Taina Turpeenniemi-Hujanen

  4. Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland

    Johan Lundin & Heikki Joensuu

  5. Department of Surgery, Helsinki University Central Hospital, Helsinki, Finland

    Caj Haglund

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  1. Anna Sivula
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  2. Anne Talvensaari-Mattila
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  3. Johan Lundin
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  4. Heikki Joensuu
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  5. Caj Haglund
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  6. Ari Ristimäki
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  7. Taina Turpeenniemi-Hujanen
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Correspondence to Anna Sivula.

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Sivula, A., Talvensaari-Mattila, A., Lundin, J. et al. Association of cyclooxygenase-2 and matrix metalloproteinase-2 expression in human breast cancer. Breast Cancer Res Treat 89, 215–220 (2005). https://doi.org/10.1007/s10549-004-0714-4

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