Prognostic significance of cyclin A in gastric cancer

Authors

  • Johanna Mrena,

    1. Department of Surgery, Helsinki University Central Hospital, Helsinki, Finland
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  • Jan-Patrik Wiksten,

    1. Department of Surgery, Helsinki University Central Hospital, Helsinki, Finland
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  • Arto Kokkola,

    1. Department of Surgery, Helsinki University Central Hospital, Helsinki, Finland
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  • Stig Nordling,

    1. Department of Pathology, Helsinki University Central Hospital, Helsinki, Finland
    2. Haartman Institute, University of Helsinki, Helsinki, Finland
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  • Caj Haglund,

    Corresponding author
    1. Department of Surgery, Helsinki University Central Hospital, Helsinki, Finland
    2. Department of Pathology, Helsinki University Central Hospital, Helsinki, Finland
    • Department of Surgery, Helsinki University Central Hospital, P.O. Box 340, 00029 HUS, Helsinki, Finland
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    • Fax: 1358-9-471-71403

  • Ari Ristimäki

    1. Department of Pathology, Helsinki University Central Hospital, Helsinki, Finland
    2. Molecular and Cancer Biology Research Program, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland
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  • There are no relationships resulting in an actual, potential or apparent conflict of interest with regard to this manuscript.

Abstract

High level of cyclin A promotes carcinogenesis, and overexpression of cyclin A has been associated with poor prognosis of cancer patients. We validated the prognostic role of cyclin A in gastric cancer and evaluated its correlation with expression of an mRNA stability factor HuR. From 342 consecutive histologically confirmed gastric cancer patients were obtained 325 representative tissue specimens for cyclin A and 316 for HuR immunohistochemistry. Specimens were stained by cyclin A and HuR specific monoclonal antibodies. Nuclear immunostaining detected in ≥≥≥≥5% of the tumor cells was considered the cut-off for cyclin A positivity. Positive HuR immunoreactivity was scored as nuclear or cytoplasmic. Associations between scores, clinicopathological factors and survival were calculated by the χ2-test, Fisher's exact test, Kaplan-Meier test and Cox model. Cyclin A detected in the nuclei of cancer cells was positive in 55% (179 of 325) of the specimens; 40% (127 of 316) of the specimens had cytoplasmic and 88% (279of 316) nuclear immunoreactivity of HuR. Cyclin A expression was an independent prognostic factor for poor survival. Cyclin A immunoreactivity was associated with old age, high stage, proximal location of the tumor, intestinal type, noncurative resection, advanced penetration depth and with nodal metastases but not distant metastases. Furthermore, cyclin A expression was associated with cytoplasmic HuR expression, whereas no association with nuclear HuR was evident. Cyclin A is an independent prognostic factor in gastric cancer, and one mechanism for its overexpression may depend on cytoplasmic localization of HuR. © 2006 Wiley-Liss, Inc.

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