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High expression of ATP-binding cassette transporter ABCC11 in breast tumors is associated with aggressive subtypes and low disease-free survival

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Abstract

ATP-binding cassette (ABC) transporters are membrane proteins that efflux various compounds from cells, including chemotherapeutic agents, and are known to affect multidrug resistance. Recent reports disagree on whether ABCC11 is a risk factor for breast tumorigenesis, but its expression in breast cancer is poorly investigated. We hypothesized that both frequency and expression levels of ABC transporters in breast tumors would vary by cancer subtype, and be associated with prognosis. Here, we constructed a tissue microarray breast tumor samples from 281 patients, and analyzed expressions of ABCB1, ABCC1, ABCC11, and ABCG2 immunohistochemically. Breast cancer subtypes were determined by immunohistochemistry of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2). Protein expression was correlated to clinicopathological characteristics, clinical follow-up, and pathological complete response to neoadjuvant chemotherapy. The tissue microarray comprised 191 luminal A (68.0 %), 17 luminal B (6.0 %), 27 HER2 (9.6 %), and 46 triple-negative (16.4 %) samples. ABCC1 and ABCC11 expressions were associated with significantly shorter disease-free survival (P = 0.027 and P = 0.003, respectively). ABCC1, ABCC11, and ABCG2, but not ABCB1, were expressed significantly more, and more frequently, in aggressive subtypes. Patients with HER2+ and triple-negative tumor subtypes that expressed high levels of ABCC11 had significantly worse disease-free survival (P = 0.017 and P < 0.001, respectively). We have shown, for the first time, that ABCC1, ABCC11, and ABCG2 are highly expressed in aggressive breast cancer subtypes, and that tumor ABCC11 expression is associated with poor prognosis.

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Acknowledgments

The authors thank Dr. Harry D. Bear (Virginia Commonwealth University) for his critical review and valuable input to improve this manuscript. Kazuaki Takabe is supported by the US National Institutes of Health (R01CA160688, K12HD055881) and a Susan G. Komen for the Cure Investigator Initiated Research Grant and Career Catalyst Research Grant (KG090510).

Ethical standards

This study was approved by the Institutional Review Board of Yokohama City University, Kanagawa, Japan.

Conflicts of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Clinical Oncology and Breast Surgery, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa, Japan

    Akimitsu Yamada, Mariko Kimura, Takashi Chishima, Yasushi Ichikawa & Itaru Endo

  2. Department of Breast and Thyroid Surgery, Yokohama City University Medical Center, 4-57 Urafunecho, Minami-ku, Yokohama, Kanagawa, Japan

    Takashi Ishikawa, Ikuko Ota & Daisuke Shimizu

  3. Department of Pathology, Yokohama City University Medical Center, 4-57 Urafunecho, Minami-ku, Yokohama, Kanagawa, Japan

    Mikiko Tanabe & Takeshi Sasaki

  4. Department of Biostatics and Epidemiology, Yokohama City University Medical Center, 4-57 Urafunecho, Minami-ku, Yokohama, Kanagawa, Japan

    Satoshi Morita

  5. Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki, Japan

    Koh-ichiro Yoshiura

  6. Division of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine, 7-402 West Hospital, 1200 E Broad Street, Richmond, VA, USA

    Kazuaki Takabe

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  1. Akimitsu Yamada
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  2. Takashi Ishikawa
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  3. Ikuko Ota
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  4. Mariko Kimura
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  6. Mikiko Tanabe
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  7. Takashi Chishima
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  8. Takeshi Sasaki
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  9. Yasushi Ichikawa
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  10. Satoshi Morita
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  11. Koh-ichiro Yoshiura
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  12. Kazuaki Takabe
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  13. Itaru Endo
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Correspondence to Takashi Ishikawa.

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Yamada, A., Ishikawa, T., Ota, I. et al. High expression of ATP-binding cassette transporter ABCC11 in breast tumors is associated with aggressive subtypes and low disease-free survival. Breast Cancer Res Treat 137, 773–782 (2013). https://doi.org/10.1007/s10549-012-2398-5

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  • DOI: https://doi.org/10.1007/s10549-012-2398-5

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