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Cyclooxygenase-2 expression in colorectal cancer liver metastases

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Abstract

Cyclooxygenase-2 (COX-2) is up-regulated in 85-90% of primary human colorectal cancers and is a putative target for the chemopreventative activity of non-steroidal anti-inflammatory drugs. However, COX-2 expression by human colorectal cancer liver metastases has been poorly characterized. We studied a consecutive series of 38 patients who underwent liver resection for metastatic disease, for whom long-term (up to 57 months), prospective follow-up data were available. Semi-quantitative immunohistochemistry for COX-2 was performed on 54 metastases from 35 patients, for whom adequate histological material was available. Diffuse cytoplasmic staining for COX-2 protein was detected in cancer cells in 100% of metastases (COX-2 score 1, n=25; score 2, n=29). There was no relationship between metastasis size or differentiation grade and the level of COX-2 protein expression. There was no difference in colorectal cancer-free or overall survival between patients with high (score 2) and low (score 1) COX-2 scores (Kaplan–Meier survival analysis and log rank test, both P=0.97). Multivariate Cox regression analysis identified age, incomplete resection and presence of extra-hepatic disease as independent predictors of disease-free and overall survival following surgery. COX-2 protein was also localized to a subset of stromal fibroblasts and mononuclear cells within metastases as well as hepatocytes from resection specimens. COX-2 protein was expressed by cancer cells in all human colorectal cancer liver metastases which were studied. Investigation of the effect of selective COX-2 inhibition on metastasis growth and metastasis cancer cell proliferation/apoptosis in vivo are warranted.

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Authors and Affiliations

  1. Molecular Medicine Unit, University of Leeds, United Kingdom

    Mark A. Hull & Keith S. Chapple

  2. Hepatobiliary unit, United Kingdom

    Stephen W. Fenwick, Giles J. Toogood & J. Peter Lodge

  3. Department of Histopathology, St James’s University Hospital, Leeds, LS9 7TF, United Kingdom

    N. Scott

Authors
  1. Mark A. Hull
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  2. Stephen W. Fenwick
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  3. Keith S. Chapple
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  4. N. Scott
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  5. Giles J. Toogood
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  6. J. Peter Lodge
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Hull, M.A., Fenwick, S.W., Chapple, K.S. et al. Cyclooxygenase-2 expression in colorectal cancer liver metastases. Clin Exp Metastasis 18, 21–27 (2000). https://doi.org/10.1023/A:1026553605636

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