High survivin expression is associated with favorable outcome in advanced primary oral squamous cell carcinoma after radiation therapy

Authors

  • Kolja Freier,

    Corresponding author
    1. Klinik für Mund-Kiefer-Gesichtschirurgie, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 400, Heidelberg, Germany
    2. Abteilung Molekulare Genetik (B060), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, Heidelberg, Germany
    • Klinik für Mund-Kiefer-Gesichtschirurgie, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 400, Heidelberg, Germany

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    • The first two authors contributed equally to this paper.

    • Fax: ++1149-6221-56-4222.

  • Susanne Pungs,

    1. Klinik für Mund-Kiefer-Gesichtschirurgie, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 400, Heidelberg, Germany
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    • The first two authors contributed equally to this paper.

  • Carsten Sticht,

    1. Klinik für Mund-Kiefer-Gesichtschirurgie, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 400, Heidelberg, Germany
    2. Abteilung Molekulare Genetik (B060), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, Heidelberg, Germany
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  • Christa Flechtenmacher,

    1. Pathologisches Institut, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 220, Heidelberg, Germany
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  • Peter Lichter,

    1. Abteilung Molekulare Genetik (B060), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, Heidelberg, Germany
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  • Stefan Joos,

    1. Abteilung Molekulare Genetik (B060), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, Heidelberg, Germany
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  • Christof Hofele

    1. Klinik für Mund-Kiefer-Gesichtschirurgie, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 400, Heidelberg, Germany
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Abstract

Oral squamous cell carcinoma (OSCC) is a solid neoplasm exhibiting aggressive tumor phenotypes with unpredictable biological behavior. Recent studies suggested that high expression of the antiapoptotic protein survivin might be associated with adverse outcome in oral cancer patients. To investigate, whether increased copy numbers of the survivin-encoding gene BIRC5 results in elevated survivin levels and whether BIRC5 and survivin could serve as progression markers in the clinical course of OSCC, tumor tissue microarray analysis was performed applying fluorescence in situ hybridization and immunohistochemistry to 296 OSCC specimens. Gene copy number gain of BIRC5 was detected in 33.9% (150/227) of cases, which correlated significantly with high UICC stage and the presence of lymph node metastases (p = 0.003 and p = 0.001, respectively), but not with unfavorable patients' outcome (p > 0.05) in multivariate analysis. High survivin expression was found in 67.3% (169/251) of cases to predict increased 5- and 10-year overall survival of patients in a multivariate model including UICC stage and age as covariables (p = 0.035 and p = 0.026, respectively). Within a subgroup of patients, who received radiation therapy (n = 121), high survivin expression was found to be the only predictor of favorable 3-, 5- and 10-year overall survival in a multivariate cox regression analysis including UICC stage and age as covariables (p = 0.001, p = 0.004 and p = 0.006, respectively). In conclusion, high survivin expression might be useful to identify OSCC patients, who would benefit from radiotherapy. © 2006 Wiley-Liss, Inc.

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