FOXP3 expression is related to high Ki-67 index and poor prognosis in lymph node-positive breast cancer patients

Oncology. 2013;85(2):128-36. doi: 10.1159/000351473. Epub 2013 Aug 13.

Abstract

Background: Recent preclinical studies have shown that Forkhead box protein 3 (FOXP3) is an important tumor suppressor gene. The clinical and prognostic implication of FOXP3 expression in breast cancer cells still remains controversial.

Methods: We evaluated the FOXP3 expression status of 183 patients who underwent curative surgery for breast cancer using the immunohistochemical assay of tissue microarray.

Results: We found FOXP3 expression in 51 out of 183 (27.9%) surgically resected breast cancer tumors, and 33 patients were scored as weak positive and 18 as strong positive. FOXP3-positive tumors were associated with significantly higher nuclear grade, higher histologic grade and a more negative estrogen receptor status. The FOXP3 expression level was independently associated with high Ki-67 index in a logistic regression model. In the node-positive subgroup, strong FOXP3 positivity was related to poor disease-free survival and disease-specific survival compared to FOXP3-negative patients, whereas there was no survival difference between FOXP3-negative and FOXP3-weak-positive patients. Multivariate analysis with adjustment for patient age and human epidermal growth factor receptor 2 status demonstrated significantly poor survival of FOXP3-strong-positive patients in node-positive patients.

Conclusion: Our results suggest that strong FOXP3 expression in breast cancer cells is associated with poor prognosis and high Ki-67 index.

MeSH terms

  • Adult
  • Aged
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy
  • Carcinoma, Ductal, Breast / metabolism*
  • Carcinoma, Ductal, Breast / mortality
  • Carcinoma, Ductal, Breast / secondary
  • Carcinoma, Ductal, Breast / therapy
  • Cell Proliferation
  • Chemotherapy, Adjuvant
  • Disease-Free Survival
  • Female
  • Forkhead Transcription Factors / metabolism*
  • Humans
  • Kaplan-Meier Estimate
  • Ki-67 Antigen / metabolism*
  • Lymphatic Metastasis
  • Middle Aged
  • Multivariate Analysis
  • Prognosis
  • Proportional Hazards Models
  • Treatment Outcome

Substances

  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Ki-67 Antigen