Tumoral FOXP 3 in Human Breast Carcinomas Has a Potentiality of Tumor Suppressor Function in Related with p 53 Tumor Suppressor Protein and Infiltrated

Background: Foxp3 is known as the most specific marker for regulatory T lymphocyte which plays an important role in immune tolerance to frustrate anti-tumor immune responses. We investigated the prognostic significance of foxp3 regulatory T lymphocyte (foxp3 Treg) infiltration in breast cancer. Methods: Immunohistochemical stainings for foxp3, CD4, and CD8 were performed on representative full tissue sections from 143 patients with invasive ductal carcinoma, no otherwise specified, which were separately quantified in tumor bed and tumor periphery. Foxp3 Treg infiltration, foxp3 Treg/CD4 T lymphocyte, and foxp3 Treg/CD8 T lymphocyte in tumor bed and tumor periphery were analyzed to examine the association with the clinicopathological factors and patient prognosis. Results: Tumor periphery was far more densely infiltrated by foxp3 Treg, CD4 and CD8 T lymphocytes. Within tumor bed and tumor periphery, high foxp3 Treg infiltration, high foxp3 Treg/ CD4 and high foxp3 Treg/CD8 were associated with unfavorable prognostic factors including high Ki-67 labeling index, higher nuclear and histologic grade. High foxp3 Treg/CD4 in tumor periphery was significantly associated with estrogen receptor and progesterone receptor negativity and triple negative breast cancer. High foxp3 infiltration and high foxp3 Treg/CD8 in tumor periphery were independent predictors of tumor recurrence and shorter disease free survival. Conclusions: High foxp3 infiltration, high foxp3 Treg/CD4 and high Treg/CD8 were valuable indicators for breast cancer with poor pathological factors and unfavorable prognosis.