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.