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Hypoxia-inducible factor-1α correlates with MET and metastasis in node-negative breast cancer

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Summary

The mechanism of tumor hypoxia promoting metastasis remains uncertain. Hypoxia-inducible factor-1α (HIF-1α) is a key mediator of the cellular response to hypoxia and binds the met promoter, resulting in increased expression of MET. In breast cancer, MET overexpression is associated with death caused by metastatic disease. Aim of this study is to investigate the role of HIF-1α in MET expression and metastasis in lymph node negative breast cancer. We recruited a homogeneous cohort of 104 patients with T1–2N0M0 breast carcinoma, who had undergone primary surgery. Fifty-three patients had distant metastases and 51 patients had no evidence of disease for more than 10 years. We analyzed the expressions of HIF-1α and MET in these patients using immunohistochemistry. HIF-1α and MET were positively correlated (Spearman’s rank correlation coefficient, 0.35; P < 0.01), were independent predictors of distant metastasis (P = 0.002 and P = 0.03, respectively), and correlated with poor 10-year disease-free survival rate (P < 0.001 for both). Furthermore, co-overexpression of HIF-1α and MET was a significant independent predictor of distant metastasis (odd radio, 10.78; P < 0.001), and patients with co-overexpression had a significantly worse 10-year disease-free survival rate. The results provide evidence that tumor hypoxia promotes metastasis through the induction of MET overexpression by HIF-1α and emphasize the promising status of HIF-1α as a therapeutic target against metastasis in node-negative breast cancer.

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Acknowledgements

This work was supported by grants from National Science Council (NSC 93-2320-B-384-003), National Cheng Kung University Hospital (NCKUH-94-013), and Chi Mei Medical Center (CMNSC-9304), Taiwan.

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Author notes

  1. Wen-Ying Lee

    Present address: Department of Pathology, Chi Mei Medical Center, 901 Chung Hwa Road, Tainan county 710, Taiwan

Authors and Affiliations

  1. Department of Radiation Oncology, National Cheng Kung University Hospital, Tainan, Taiwan

    Helen H. W. Chen

  2. Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan

    Wu-Chou Su

  3. Department of Institute of Molecular Medicine, National Cheng Kung University, Tainan, Taiwan

    Wu-Chou Su

  4. Department of Surgery, National Cheng Kung University Hospital, Tainan, Taiwan

    Pin-Wen Lin

  5. Department of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan

    Pin-Wen Lin

  6. Department of Environmental and Occupational Health, National Cheng Kung University, Tainan, Taiwan

    How-Ran Guo

  7. Department of Pathology, National Cheng Kung University Hospital, Tainan, Taiwan

    Wen-Ying Lee

  8. Department of Pathology, College of Medicine, Taipei Medical University, Taipei, Taiwan

    Wen-Ying Lee

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  1. Helen H. W. Chen
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Correspondence to Wen-Ying Lee.

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Chen, H.H.W., Su, WC., Lin, PW. et al. Hypoxia-inducible factor-1α correlates with MET and metastasis in node-negative breast cancer. Breast Cancer Res Treat 103, 167–175 (2007). https://doi.org/10.1007/s10549-006-9360-3

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  • DOI: https://doi.org/10.1007/s10549-006-9360-3

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