B7-H3 expression in colorectal cancer: Nuclear localization strongly predicts poor outcome in colon cancer

Authors

  • Vibeke Anett Ingebrigtsen,

    Corresponding author
    1. Department of Tumor Biology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
    2. Faculty of Medicine, Institute for Clinical Medicine, University of Oslo, Oslo, Norway
    • Department of Tumor Biology, Oslo University Hospital, The Norwegian Radium Hospital, P.O. Box 4950 Nydalen, N-0424 Oslo, Norway
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    • Tel.: [047-22-78-23-15], Fax: +[047-2-78-18-95]

  • Kjetil Boye,

    1. Department of Tumor Biology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
    2. Department of Oncology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
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  • Christina Tekle,

    1. Department of Tumor Biology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
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  • Jahn Martin Nesland,

    1. Faculty of Medicine, Institute for Clinical Medicine, University of Oslo, Oslo, Norway
    2. Department of Pathology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
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  • Kjersti Flatmark,

    1. Department of Tumor Biology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
    2. Department of Gastroenterological Surgery, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
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  • Øystein Fodstad

    Corresponding author
    1. Department of Tumor Biology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
    2. Faculty of Medicine, Institute for Clinical Medicine, University of Oslo, Oslo, Norway
    • Department of Tumor Biology, Oslo University Hospital, The Norwegian Radium Hospital, P.O. Box 4950 Nydalen, N-0424 Oslo, Norway
    Search for more papers by this author
    • Tel.: [047-22-78-23-15], Fax: +[047-2-78-18-95]


Abstract

In colorectal cancer there is a need for molecular markers that can complement the histopathological staging in predicting the likelihood of disease recurrence following curatively intended surgery. B7-H3 is an immunoregulatory protein shown to be overexpressed in several cancer forms, often associated with more advanced disease and poor prognosis. We wanted to examine whether B7-H3 could be a potential prognostic marker in colorectal cancer. Paraffin-embedded samples from 277 colorectal cancer patients were immunostained with anti-B7-H3 antibody. B7-H3 was expressed in the tumor cell cytoplasm and cell membrane in 62% and 46% of the samples, respectively. Unexpectedly, B7-H3 was expressed in the nucleus in 30% of the tumors. The nuclear localization was confirmed by Western immunoblotting of subcellular fractions. Importantly, in colon cancer, nuclear B7-H3 expression was independently and significantly associated with reduced metastasis-free, disease-specific and overall survival. B7-H3 expression in tumor-associated vasculature and fibroblasts was observed in the majority of samples, and endothelial B7-H3 expression was also significantly associated with poor outcome in colon cancer. In rectal cancer patients, the only significant association was between fibroblast B7-H3 expression and shorter metastasis-free survival. Few significant associations to clinicopathological parameters were seen. The results indicate that nuclear B7-H3 might be involved in colon cancer progression and metastasis, and suggest that nuclear B7-H3 could become a useful prognostic marker in colon cancer.

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