FOXP3 expression of micrometastasis-positive sentinel nodes in breast cancer patients

Abstract

Abstract. A number of methods have been established for identifying sentinel nodes (SNs). In the present study, we attempted to clarify the immunological status of SNs with or without micrometastasis in breast cancer patients. SNs were identified by the dye-and Á probe-guided method. Total RNA was extracted from the SNs, and the expression of T-BET, GATA-3, and FOXP3 were evaluated using quantitative realtime reverse transcriptase-polymerase chain reaction (RT-PCR). Micrometastasis was identified as microscopically negative but positive by RT-PCR specific for mammaglobin. Of 88 patients, 17 (19.3%) showed positive metastasis in SNs (pN1, 14; pN2, 3). Of the 71 metastasis-negative SNs, 11 showed positive bands on RT-PCR specific for mammaglobin [pN0(mol+)]. There was no significant correlation among clinicopathological features with or without micrometastasis. Immunological parameters were compared among the 60 pN0, 11 pN0(mol+), and 17 pN1-2. Although T-BET expression was higher in pN0(mol+) than pN0, FOXP3 expression was also higher in pN0(mol+) than pN0. In pN1-2, T-BET expression decreased compared with pN0(mol+), but FOXP3 expression did not. On the other hand, GATA-3 expression inversely increased in pN1-2 compared with pN0(mol+). In patients with breast cancer, micrometastasis can stimulate Th1 response in SNs. However, the Treg cell response is also induced at the micrometastasis level and persists during the progression of metastasis in SNs. Then, the shift in the Th1/Th2 balance may preferentially lean toward Th2 responses in pN1-2 SNs and suppress antitumor immune responses. Micrometastasis [pN0(mol+)] is a status immunologically distinguishable from pN0 and pN1-2.

Heat Shock Protein 27 Differentiates Tolerogenic Macrophages That May Support Human Breast Cancer Progression

“…These data indicate that Hsp27-differentiated MACs may have induced the preferential differentiation of naive T cells to IL-13-producing T cells (Th2) prior to tolerance induction. Although a Th1!Th2 shift, as reported in breast cancer (44,45), is not confirmed in our current experiments, they certainly indicate that Th1 cells are more affected than Th2 cells during a coculture of Hsp27 or M-CSF þ Hsp27-differentiated MACs with autologous T cells.…”

Regulatory T cells and breast cancer: implications for immunopathogenesis

“…It was indicated that FoxP3 + Tregs increased in the microenvironment of sentinel lymph nodes along with pathologically undetectable micrometastasis and were an independent prognostic predictor in patients with node-negative breast cancer [90]. In this context, it was observed that Treg response was induced at the micrometastasis level and persisted during metastasis progression in sentinel nodes in breast cancer patients [91].…”

Investigations on the clinical significance of FOXP3 protein expression in cervical oesophageal cancer and the number of FOXP3+ tumour-infiltrating lymphocytes

“…However, there have been contradictory reports about the expression and functions of FOXP3 in breast cancer cells. Matsuura et al 10 found that the FOXP3 mRNA and protein were highly expressed in tumour tissue from breast cancer patients, and that expression was closely associated with tumour recurrence and overall survival rate. We suggest that that FOXP3 could be a new prognostic factor for breast cancer.…”

“…[6][7][8] Studies have found that some tumour cells expressing FOXP3 at a high level have immunosuppressive effects similar to those of Treg cells; through such an effect or other, unknown mechanisms, the immune killing of tumour cells (such as pancreatic cancer cells and breast cancer cells) may be directly or indirectly inhibited, resulting in escape from immune surveillance. [9][10][11] These findings have provided new directions for studying of the mechanism of tumour immune escape. However, there have been few studies on squamous cell carcinoma, especially of the head and neck.…”