Intratumoral FOXP3 expression in infiltrating breast carcinoma: Its association with clinicopathologic parameters and angiogenesis.

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Abstract
The activity of T regulatory cells (Tregs) is known to be closely associated with the expression of forkhead/winged helix transcription factor, FOXP3. To determine, whether accumulation and activation of intratumoral Tregs help in the progression of breast carcinoma, we have analyzed the intratumoral expression of FOXP3 in invasive breast carcinoma and compared it with its level in ductal carcinoma in situ (DCIS) and adjacent normal tissue with the main aim of using this factor as marker of tumor progression. Intratumoral FOXP3 levels were correlated with the levels of transforming growth factor β1 (TGF-β1), vascular endothelial growth factor (VEGF, an invasogenic and angiogenic growth factor) and intratumoral microvessel density (IMD, a prognostic marker for angiogenesis). We also analyzed whether FOXP3 gene expression correlated with other clinicopathological variables like age, tumor stage, histological grade and lymph node metastasis. Infiltrating cancers had higher FOXP3 transcription (7.43±3.44) than did ductal carcinoma in situ (4.27±1.97, p<0.05) and normal tissues (3.51±1.22, p<0.001). Intratumoral FOXP3 expression was significantly higher in patients with stage III disease (TNM classification) compared to patients who had stage II disease (p=0.037). In infiltrating carcinoma, a significant positive correlation between FOXP3 expression and TGF-β1 expression was noted (p<0.001). Furthermore, a positive correlation between FOXP3 expression with VEGF expression and IMD values was also detected, however, statistically that was non-significant. A linear association of intratumoral FOXP3 expression with invasion, size and vascularity suggests a utility of FOXP3, an indicator of Treg activity as a marker of tumor progression and metastasis in breast carcinoma.