Expression Of FOXP3 And TGF-β1 In Breast Cancer And Their Significance

Backgroud: Breast carcinoma is one of the most common malignant tumors in females, which increases at the rate of 4% every year and ranks first in female malignant tumors and greatly threatens the health of females. From immunology and molecular biology perspective, studying the impact of prognostic factors in breast carcinoma will help us further understand the biological behavior of breast carcinoma. FOXP3 is a member of forkhead/winged-helix transcription factor family, early studies have showed its expression was found in CD4+CD25+ regulatory T cells specifically, and is closely related to the development and function of CD4+CD25+ regulatory T cells. To some extent, it reflects the level and function of CD4+CD25+ regulatory T cells. Subsequent study found that FOXP3 was expressd in pancreatic cancer cells and melanoma cells. The expression of FOXP3 in breast carcinoma cells and lymphocytes infiltrating in breast carcinoma mesenchyma and their biological significance to breast carcinoma are not yet known, therefore it is worth to be further studied.Objective: To detect the FOXP3 mRNA and protein expression, FOXP3-positive lymphocytes infiltration and the protein expression of TGF-β1 in breast carcinoma, and to analysis their relationships with clinicopathologic features and prognosis of breast carcinoma.Methods: The protein expression of FOXP3 in breast cancer cells, FOXP3-positive lymphocytes infiltration and TGF-β1 and the mRNA expression of FOXP3 were detected by immunohistochemistry and in situ hybridization respectively in 92 cases of breast carcinoma and 26 cases of breast tissues adjacent to carcinoma by using tissue microarray. Results:1. Positive stainings for FOXP3 mRNA were found in breast carcinoma cells and breast epithelia. Positive stainings for FOXP3 mRNA were also found in a few lymphocytes infiltrating in breast carcinoma mesenchyma. The expression of FOXP3 mRNA in breast carcinoma parechyma was significantly higher than that in breast tissues adjacent to carcinoma (46.7% vs 3.8%,P <0.01).2. Positive stainings for FOXP3 protein were found in breast cancer cells and breast epithelia, which were mainly located in nuclei of cells. Positive stainings for FOXP3 protein were also found in lymphocytes infiltrating in breast cancer mesenchyma. The protein expression of FOXP3 in breast carcinoma parechyma was significantly higher than that in breast tissues adjacent to carcinoma (52.2% vs 7.7%, P <0.01). FOXP3-positive lymphocytes infiltrating in breast carcinoma mesenchyma were significantly higher than that in breast tissues adjacent to carcinoma (32.7% vs 7.7%, P <0.01).3. There were positive relationships between FOXP3 mRNA expression and its protein expression in breast carcinoma parechyma and breast tissues adjacent to carcinoma (r=0.897, r=0.693, P<0.01).4. There were no correlations between the expression of FOXP3 protein in breast cancer parechyma and FOXP3-positive lymphocytes infiltrating in the breast carcinoma mesenchyma (P >0.05).5. The protein and mRNA expression of FOXP3 in breast carcinoma parechyma were positively correlated to lymph node metastasis and pTNM staging, but no correlation to five-year survival of breast carcinoma.6. FOXP3-positive lymphocytes infiltrating in breast cancer mesenchyma were positively correlated to lymph node metastasis, histological grading, pTNM staging and c-erbB-2 overexpression, but no correlations to five-year survival of breast carcinoma. 7. The protein expression of TGF-β1 in breast carcinoma tissues was significantly higher than that in breast tissues adjacent to carcinoma (P <0.01). It was positively correlated to lymph node metastasis, histological grading and pTNM staging, but no correlations to five-year survival of breast carcinoma.8. The protein expression of TGF-β1 in breast carcinoma tissues was positively correlated to that of FOXP3-positive lymphocytes infiltrating in the breast carcinoma mesenchyma (r=0.342,P <0.05).9. The protein expression of TGF-β1 in breast carcinoma tissues was positively correlated to that of FOXP3 in breast carcinoma parechyma (r=0.249,P <0.05).Conclusions:1. FOXP3-positive lymphocytes which have immune inhibition function may play a role in immune escape of breast carcinoma.2. The increased expression of FOXP3 in breast carcinoma parechyma was closely related to invasion and metastasis of breast carcinoma.3. TGF-β1 may be a potential marker for evaluating differentiation and progression of breast carcinoma.4. It was further confirmed that increasing FOXP3-positive lymphocytes in tumor microenvironment were regulated by TGF-β1.