title: Zonal difference and prognostic significance of foxp3 regulatory T cell infiltration in breast cancer.
abstract: OBJECTIVE
  Forkhead box P3 (Foxp3) is known as the most specific marker for regulatory T lymphocytes, which play an important role in immune tolerance to disturb antitumor immunity. The present study aimed to investigate the prognostic significance of Foxp3 regulatory T lymphocyte (Foxp3 Treg) infiltration in breast cancer.
  
  
  METHODS
  Immunohistochemical studies with Foxp3, CD4, and CD8 were performed on representative full tissue sections from 143 patients with invasive ductal carcinoma, not otherwise specified. Foxp3 Treg infiltration and the ratios between Foxp3 Treg and CD4 or CD8 T cells were separately analyzed for the tumor bed and tumor periphery to evaluate their association with different clinicopathological parameters and patients' outcome.
  
  
  RESULTS
  The tumor periphery was considerably more densely infiltrated by Foxp3 Treg, CD4, and CD8 T cells than the tumor bed. Unfavorable clinicopathological parameters (a Ki-67 labeling index of ≥14%, a worse histologic grade, a worse nuclear grade, hormone receptor negativity, human epidermal growth factor receptor 2 positivity, and tumor recurrence) were associated with increased Foxp3 Treg infiltration and a high ratio between Foxp3 Treg and CD4/CD8 T cells. In the tumor periphery, as Foxp3 Treg infiltration and the Foxp3 Treg/CD8 ratio increased, patients' 5-year disease-free survival rate decreased.
  
  
  CONCLUSIONS
  The infiltration densities of Foxp3 Treg, CD4, and CD8 T cells were markedly different between the tumor bed and periphery. Besides the absolute count of Foxp3 Treg, the ratio between Foxp3 Treg and effector T cells was a significant prognostic factor in breast cancer.
authors.affiliation: Department of Pathology, Ewha Womans University School of Medicine, Seoul, Korea.
authors.forename: Sewha
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Surgery, Ewha Womans University School of Medicine, Seoul, Korea.
authors.forename: Anbok
authors.initials: A
authors.lastname: Lee
authors.affiliation: Department of Surgery, Ewha Womans University School of Medicine, Seoul, Korea.
authors.forename: Woosung
authors.initials: W
authors.lastname: Lim
authors.affiliation: Department of Pathology, Ewha Womans University School of Medicine, Seoul, Korea.
authors.forename: Sanghui
authors.initials: S
authors.lastname: Park
authors.affiliation: Department of Pathology, Ewha Womans University School of Medicine, Seoul, Korea.
authors.forename: Min Sun
authors.initials: MS
authors.lastname: Cho
authors.affiliation: Department of Pathology, Ewha Womans University School of Medicine, Seoul, Korea.
authors.forename: Heasoo
authors.initials: H
authors.lastname: Koo
authors.affiliation: Department of Surgery, Ewha Womans University School of Medicine, Seoul, Korea.
authors.forename: Byung-In
authors.initials: BI
authors.lastname: Moon
authors.affiliation: Department of Pathology, Ewha Womans University School of Medicine, Seoul, Korea.
authors.forename: Sun Hee
authors.initials: SH
authors.lastname: Sung
keywords: Breast neoplasms; Foxp3 protein; Humans; Regulatory; T-lymphocyte
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