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COX-2 is associated with proliferation and apoptosis markers and serves as an independent prognostic factor in gastric cancer

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Tumor Biology

Abstract

Cyclooxygenase-2 (COX-2) is an important factor in gastric carcinogenesis, and COX-2 expression in gastric cancer patients correlates with prognosis. We have now studied the impact of COX-2 in comparison to six other tissue tumor markers, DNA index, and S-phase fraction (SPF) in a large series of gastric cancer specimens. From 342 consecutive patients, 337 archival tissue specimens were available for immunohistochemistry of COX-2, HuR, cyclin A, MMP-2, p53, p21, and Ki-67 and 313 for analysis of DNA index and S-phase fraction by flow cytometry. Associations between factors were assessed by chi-square test and survival analysis by the Kaplan–Meier method and Cox model. A significant association emerged between of COX-2 and p53 (p < 0.0001), Ki-67 (p = 0.013), DNA ploidy (p < 0.0001), and SPF (p < 0.0001). In an extended multivariate analysis, COX-2 and p53 expression were independent prognostic factors for poor survival, in addition to high stage and non-curative surgery. In gastric cancer, COX-2 expression associated with markers for apoptosis and proliferation, and furthermore, it was confirmed that COX-2 and p53 are strong prognostic indicators.

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Acknowledgments

Technical assistance of Päivi Peltokangas, Tuija Hallikainen, Elina Laitinen, and Elina Aspiala is warmly acknowledged. This study has been supported by grants from the Finnish Cancer Society, Finska Läkaresällskapet, Medicinska Understödsföreningen Liv och Hälsa, Helsinki University Research Funds, Helsinki University's Research Funds, the Academy of Finland, and the Sigrid Jusélius Foundation.

Competing interests

There are no financial relationships resulting in an actual, potential or apparent conflict of interest with regard to this manuscript.

Authors’ contributions

JM participated in immunostaining of tissue samples, carried out the immunohistochemical scoring and drafted the manuscript. J-PW participated in collection of clinical data and performed statistical analysis. AK collected clinical data and helped with study design. SN, as senior pathologist, confirmed scoring of immunostainings, carried out TNM staging, and made possible preparation of representative tissue microarray sections. AR and CH conceived and coordinated the study and performed the final drafting of the manuscript, and stainings were performed in the laboratory of CH.

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Authors and Affiliations

  1. Department of Surgery, Helsinki University Central Hospital, P.O. Box 340, 00029 HUS, Helsinki, Finland

    Johanna Mrena, Jan-Patrik Wiksten, Arto Kokkola & Caj Haglund

  2. Department of Pathology, Helsinki University Central Hospital, Helsinki, Finland

    Stig Nordling, Ari Ristimäki & Caj Haglund

  3. Genome-Scale Biology Research Program, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland

    Ari Ristimäki

  4. Department of Pathology, University of Oulu and Oulu University Hospital, Oulu, Finland

    Ari Ristimäki

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  1. Johanna Mrena
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  2. Jan-Patrik Wiksten
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Correspondence to Caj Haglund.

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Ari Ristimäki and Caj Haglund have equal last authorship.

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Mrena, J., Wiksten, JP., Kokkola, A. et al. COX-2 is associated with proliferation and apoptosis markers and serves as an independent prognostic factor in gastric cancer. Tumor Biol. 31, 1–7 (2010). https://doi.org/10.1007/s13277-009-0001-4

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  • DOI: https://doi.org/10.1007/s13277-009-0001-4

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