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Molecular and Clinical Oncology
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Article

FOXP3 expression in tumor cells and tumor-infiltrating lymphocytes is associated with breast cancer prognosis

  • Authors:
    • Miki Takenaka
    • Naoko Seki
    • Uhi Toh
    • Satoshi Hattori
    • Akihiko Kawahara
    • Tomohiko Yamaguchi
    • Keiko Koura
    • Ryuji Takahashi
    • Hiroko Otsuka
    • Hiroki Takahashi
    • Nobutaka Iwakuma
    • Shino Nakagawa
    • Teruhiko Fujii
    • Tetsuro Sasada
    • Rin Yamaguchi
    • Hirohisa Yano
    • Kazuo Shirouzu
    • Masayoshi Kage
  • View Affiliations / Copyright

    Affiliations: Department of Pathology, School of Medicine, Kurume University, Kurume, Fukuoka 830-0011, Japan, Research Center for Innovative Cancer Therapy, Kurume University, Kurume, Fukuoka 830-0011, Japan, Department of Surgery, School of Medicine, Kurume University, Kurume, Fukuoka 830-0011, Japan, Biostatistical Center, Kurume University, Kurume, Fukuoka 830-0011, Japan, Department of Diagnostic Pathology, Kurume University Hospital, Kurume, Fukuoka 830-0011, Japan, Multidisciplinary Treatment Center, Kurume University Hospital, Kurume, Fukuoka 830-0011, Japan, Department of Immunology, School of Medicine, Kurume University, Kurume, Fukuoka 830-0011, Japan
  • Pages: 625-632
    |
    Published online on: April 26, 2013
       https://doi.org/10.3892/mco.2013.107
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Abstract

The forkhead box protein 3 (FOXP3) transcription factor is highly expressed in tumor cells as well as in regulatory T cells (Tregs). It plays a tumor-enhancing role in Tregs and suppresses carcinogenesis as a potent repressor of several oncogenes. The clinical prognostic value of FOXP3 expression has not yet been elucidated. In this study, immunohistochemistry was used to investigate the prognostic significance of FOXP3 expression in tumor cells and tumor-infiltrating lymphocytes (TILs) in breast cancer patients. Of the 100 tumor specimens obtained from primary invasive breast carcinoma, 63 and 57% were evaluated as FOXP3+ tumor cells and as being highly infiltrated by FOXP3+ lymphocytes, respectively. Although FOXP3 expression in tumor cells was of no prognostic significance, FOXP3+ lymphocytes were significantly associated with poor overall survival (OS) (n=98, log-rank test P=0.008). FOXP3 exhibited a heterogeneous subcellular localization in tumor cells (cytoplasm, 31%; nucleus, 26%; both, 6%) and, although cytoplasmic FOXP3 was associated with poor OS (P=0.058), nuclear FOXP3 demonstrated a significant association with improved OS (p=0.016). Furthermore, when patients were grouped according to their expression of tumor cytoplasmic FOXP3 and lymphocyte FOXP3, there were notable differences in the Kaplan-Meier curves for OS (P<0.001), with a high infiltration of FOXP3+ lymphocytes accompanied by a cytoplasmic FOXP3+ tumor being the most detrimental phenotype. These findings indicated that FOXP3 expression in lymphocytes as well as in tumor cells may be a prognostic marker for breast cancer. FOXP3 in tumor cells may have distinct biological activities and prognostic values according to its localization, which may help establish appropriate cancer treatments.
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Copy and paste a formatted citation
Spandidos Publications style
Takenaka M, Seki N, Toh U, Hattori S, Kawahara A, Yamaguchi T, Koura K, Takahashi R, Otsuka H, Takahashi H, Takahashi H, et al: FOXP3 expression in tumor cells and tumor-infiltrating lymphocytes is associated with breast cancer prognosis. Mol Clin Oncol 1: 625-632, 2013.
APA
Takenaka, M., Seki, N., Toh, U., Hattori, S., Kawahara, A., Yamaguchi, T. ... Kage, M. (2013). FOXP3 expression in tumor cells and tumor-infiltrating lymphocytes is associated with breast cancer prognosis. Molecular and Clinical Oncology, 1, 625-632. https://doi.org/10.3892/mco.2013.107
MLA
Takenaka, M., Seki, N., Toh, U., Hattori, S., Kawahara, A., Yamaguchi, T., Koura, K., Takahashi, R., Otsuka, H., Takahashi, H., Iwakuma, N., Nakagawa, S., Fujii, T., Sasada, T., Yamaguchi, R., Yano, H., Shirouzu, K., Kage, M."FOXP3 expression in tumor cells and tumor-infiltrating lymphocytes is associated with breast cancer prognosis". Molecular and Clinical Oncology 1.4 (2013): 625-632.
Chicago
Takenaka, M., Seki, N., Toh, U., Hattori, S., Kawahara, A., Yamaguchi, T., Koura, K., Takahashi, R., Otsuka, H., Takahashi, H., Iwakuma, N., Nakagawa, S., Fujii, T., Sasada, T., Yamaguchi, R., Yano, H., Shirouzu, K., Kage, M."FOXP3 expression in tumor cells and tumor-infiltrating lymphocytes is associated with breast cancer prognosis". Molecular and Clinical Oncology 1, no. 4 (2013): 625-632. https://doi.org/10.3892/mco.2013.107
Copy and paste a formatted citation
x
Spandidos Publications style
Takenaka M, Seki N, Toh U, Hattori S, Kawahara A, Yamaguchi T, Koura K, Takahashi R, Otsuka H, Takahashi H, Takahashi H, et al: FOXP3 expression in tumor cells and tumor-infiltrating lymphocytes is associated with breast cancer prognosis. Mol Clin Oncol 1: 625-632, 2013.
APA
Takenaka, M., Seki, N., Toh, U., Hattori, S., Kawahara, A., Yamaguchi, T. ... Kage, M. (2013). FOXP3 expression in tumor cells and tumor-infiltrating lymphocytes is associated with breast cancer prognosis. Molecular and Clinical Oncology, 1, 625-632. https://doi.org/10.3892/mco.2013.107
MLA
Takenaka, M., Seki, N., Toh, U., Hattori, S., Kawahara, A., Yamaguchi, T., Koura, K., Takahashi, R., Otsuka, H., Takahashi, H., Iwakuma, N., Nakagawa, S., Fujii, T., Sasada, T., Yamaguchi, R., Yano, H., Shirouzu, K., Kage, M."FOXP3 expression in tumor cells and tumor-infiltrating lymphocytes is associated with breast cancer prognosis". Molecular and Clinical Oncology 1.4 (2013): 625-632.
Chicago
Takenaka, M., Seki, N., Toh, U., Hattori, S., Kawahara, A., Yamaguchi, T., Koura, K., Takahashi, R., Otsuka, H., Takahashi, H., Iwakuma, N., Nakagawa, S., Fujii, T., Sasada, T., Yamaguchi, R., Yano, H., Shirouzu, K., Kage, M."FOXP3 expression in tumor cells and tumor-infiltrating lymphocytes is associated with breast cancer prognosis". Molecular and Clinical Oncology 1, no. 4 (2013): 625-632. https://doi.org/10.3892/mco.2013.107
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