FOXP3 Expression Is Related to High Ki-67 Index and Poor Prognosis in Lymph Node-Positive Breast Cancer Patients

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.ope