Clinicopathological Significance of FOXP3 Expression in Esophageal Squamous Cell Carcinoma

The expression of transcription factor forkhead box protein 3 (FOXP3), a master control gene for regulatory T cells, has been reported to influence patient survival. However, there have been few reports of the relationship between FOXP3 positive cells and esophageal squamous cell carcinoma (ESCC). The aim of this study was to clarify the prognostic value of FOXP3 expression in ESCC. Ninety-five patients who were diagnosed with primary ESCC and underwent subtotal esophagectomy during 2009 and 2010 were retrospectively analyzed. Deepest sections from each tumor were selected for immunohistochemistry and the number of FOXP3 positive cells was counted. The median number was used as a cutoff to divide into FOXP3 positive and FOXP3 negative subgroups. Relationships between FOXP3 expression and clinicopathological features, disease-free survival (DFS) and overall survival (OS) were determined. Statistical values of p < 0.05 were considered significant. FOXP3 positive cells were found in all 95 cases and the number of FOXP3 positive cells was significantly higher in the peri-tumor compartment than in the intra-tumor compartment (p = 0.0006). For this reason, the peri-tumor compartment numbers were used for all of the association studies. Results showed that the FOXP3 positive group had a significantly larger mean tumor size (43.8 ± 4.1mm vs 29.1 ± 4.0mm, p = 0.0055), and the FOXP3 negative group had a significantly higher percentage of deep invasion (T2, T3, T4)(p = 0.0399). There was no significant association for DFS, however, for OS the FOXP3 positive group demonstrated a significantly better prognosis (p = 0.0024). Multivariate analysis showed that peri-tumor FOXP3 expression is an independent prognostic factor for OS (p = 0.0035). Peri-tumoral FOXP3 expression is an independent and favorable prognostic factor for ESCC