An evaluation of the clinical significance of FOXP3+ infiltrating cells in human breast cancer
Tóm tắt
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 (r
s = 0.37, P < 0.001) and ER negativity (Mann–Whitney U test, P < 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 (P = 0.012, log rank = 6.36). This association was found for intratumoural FOXP3+ and for tumour-adjacent stromal FOXP3+-cells (tumour-cell associated FOXP3, P = 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.
Tài liệu tham khảo
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