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Cyclooxygenase-2 expression in primary breast cancers predicts dissemination of cancer cells to the bone marrow

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Abstract

Purpose Cyclooxygenase-2 (COX2) plays a role in breast cancer progression at various stages starting from pre-malignant phenotype to clinical metastasis. Breast cancer metastasizes commonly to the bone and preclinical studies suggest an involvement of COX2 in this process. Detection of disseminated tumor cells in the bone marrow of patients at the time of surgery correlates with the subsequent development of clinical bone metastasis. Therefore, to investigate whether COX2 is important for breast cancer metastasis in humans, we analyzed COX2 protein expression by immunostaining of primary tumors from 112 operable stages I, II, or III patients and determined its correlation with bone marrow micrometastasis (BMM). Methods We detected COX2 protein in primary tumors by immunostaining with a monoclonal antibody, and tumor cells present in the bone marrow by immunostaining for epithelial cytokeratins and by morphological criteria. Results COX2 expression in primary breast cancer correlated with BMM in a highly statistically significant manner (P = 0.006). Our statistical analyses of correlations of the COX2 positivity in primary tumor with other clinically relevant indicators revealed that COX2 positivity correlates with high nuclear grade (P = 0.0004). Furthermore, we were able to detect COX2 protein in BMM by immunostaining. Conclusions These studies indicate that COX2 produced in primary breast cancer cells may be vital to the initial development of BMM that may subsequently lead to osteolytic bone metastases in patients with breast cancer, and that COX2 inhibitors may be useful in halting this process.

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Acknowledgements

These studies were supported in part by the grants DK067682 (AL) and CA16672 (Core) from the National Institutes of Health and DAMD17-03-1-0669 (AL) from the United States Army Medical Research and Material Command. We thank Gabriel Hortobagyi for helpful comments on the manuscript.

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Authors and Affiliations

  1. Department of Surgical Oncology, Unit 444, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA

    Anthony Lucci, Balraj Singh, Isabelle Bedrosian, Funda Meric-Bernstam, Kailash Mosalpuria, Ashutosh Lodhi & Laura Vincent

  2. Advanced Research Center for Microscopic Disease, The University of Texas M.D. Anderson Cancer Center, Houston, TX, 77030, USA

    Anthony Lucci, Savitri Krishnamurthy, Balraj Singh, James Reuben & Massimo Cristofanilli

  3. Department of Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, 77030, USA

    Savitri Krishnamurthy

  4. Department of Hematopathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, 77030, USA

    James Reuben

  5. Department of Quantitative Sciences, The University of Texas M.D. Anderson Cancer Center, Houston, TX, 77030, USA

    Kristine Broglio

  6. Department of Breast Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, 77030, USA

    Massimo Cristofanilli

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  1. Anthony Lucci
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Correspondence to Anthony Lucci.

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Lucci, A., Krishnamurthy, S., Singh, B. et al. Cyclooxygenase-2 expression in primary breast cancers predicts dissemination of cancer cells to the bone marrow. Breast Cancer Res Treat 117, 61–68 (2009). https://doi.org/10.1007/s10549-008-0135-x

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  • DOI: https://doi.org/10.1007/s10549-008-0135-x

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