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Tumor Specific VEGF-A and VEGFR2/KDR Protein are Co-expressed in Breast Cancer

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Abstract

Angiogenesis is a prognostic indicator in primary breast cancer regulated by specific angiogenic factors and their receptors. Vascular endothelial growth factor-A (VEGF-A), so far considered the most important, acts through dimerization of the receptor VEGFR2/KDR within the receptor tyrosine kinase family of VEGF receptors. In order to study the interplay between VEGF-A and VEGFR2/KDR in breast cancer we evaluated their expression by immunohistochemistry in 102 breast cancers organized in a tumor tissue array system allowing semi-quantitative evaluation of cytoplasmatic staining intensity. In addition, VEGF-A165 was analyzed by an enzyme immuno assay (ELISA) in protein extracts prepared from frozen tissue from 98 of 102 tumors included in the array. Cytoplasmatic staining of VEGF of varying intensity was observed in all samples and correlated with the ELISA results of VEGF content (p = 0.007). Interestingly, VEGFR2/KDR expression correlated with VEGF expression using immunohistochemistry, indicating that VEGF and VEGFR2/KDR may be co-expressed in breast cancer. Furthermore, high levels of VEGF-A165 in the protein extracts was associated with impaired short time survival but not long term survival whereas immunohistochemically assessed VEGF and VEGFR2/KDR were not significantly associated with survival. In summary, immunohistochemically based analysis of VEGF using a tumor tissue array system seems to be a useful method for VEGF quantification in breast cancer here validated using an ELISA based method. The tumor tissue array system enables opportunities of simultaneous analysis of markers engaged in angiogenesis justifying further studies using larger series of tumors.

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Authors and Affiliations

  1. Department of Surgery, Helsingborgs Lasarett, Helsingborg, Sweden

    Lisa Rydén & Per-Ebbe Jönsson

  2. Department of Oncology, Radiumhemmet, Karolinska Institute and Hospital, Stockholm, Sweden

    Barbro Linderholm

  3. Department of Medical Biosciences, Division of Pathology, Umeå University, Sweden

    Niels Hilmer Nielsen

  4. Department of Surgical and Perioperative Sciences, Division of Surgery, Umeå University, Sweden

    Stefan Emdin

  5. Department of Laboratory Medicine, Division of Pathology, Lund University, Malmö University Hospital, Malmö, Sweden

    Göran Landberg

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  1. Lisa Rydén
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  2. Barbro Linderholm
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  3. Niels Hilmer Nielsen
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  4. Stefan Emdin
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  5. Per-Ebbe Jönsson
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  6. Göran Landberg
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Rydén, L., Linderholm, B., Nielsen, N.H. et al. Tumor Specific VEGF-A and VEGFR2/KDR Protein are Co-expressed in Breast Cancer. Breast Cancer Res Treat 82, 147–154 (2003). https://doi.org/10.1023/B:BREA.0000004357.92232.cb

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  • DOI: https://doi.org/10.1023/B:BREA.0000004357.92232.cb

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