An evaluation of the clinical significance of FOXP3 infiltrating cells in human breast cancer
Résumé
Studies in mice have shown that thymic-derived CD4+ CD25+ regulatory T cells (T reg; FOXP3 lymphocytes) inhibit an antitumour immune response. Additional studies have also reported that the T reg population increases in peripheral blood and tumour tissues from patients with cancer. However, the relationship between the T reg population and the patient prognosis remains controversial. Our aim was to determine the prognostic value of T reg cell density in breast cancer using immunohistochemical assessment of FOXP3, which has been shown to be the optimal marker for T regs. Tissue microarrays were used, and the density of FOXP3 cells was determined in a series of 1445 cases of well-characterised primary invasive breast carcinoma cases with long-term follow up. FOXP3 cell numbers were counted in tumour nests, in tumour-adjacent stroma, and in distant stroma. The total number of FOXP3 cells significantly correlated with higher tumour grade ( = 0.37, < 0.001) and ER negativity (Mann-Whitney test, < 0.001). In addition, FOXP3 infiltration positively correlated with HER2 expression and basal phenotype subclass. On univariate analysis, FOXP3 cells were associated with a worse prognosis ( = 0.012, log rank = 6.36). This association was found for intratumoural FOXP3 and for tumour-adjacent stromal FOXP3-cells (tumour-cell associated FOXP3, = 0.001 and log rank 10.35). However, the number of FOXP3 cells was not found to be an independent prognostic factor in multivariate analysis. We therefore conclude that FOXP3 infiltrating cells do not have a dominant role in breast cancer prognosis and suggest that other inflammatory cell subsets may be more critical variables.
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