Expression of and correlation between BCL6 and ZEB family members in patients with breast cancer

Abstract

B-cell lymphoma 6 (BCL6), a proto-oncogene, is an evolutionarily conserved zinc finger protein that functions as a transcriptional repressor. BCL6 is the master regulator of B-lymphocyte development, and it has been reported that BCL6 may serve an important role in breast cancer progression. The aim of the present study was to investigate the expression of BCL6, zinc finger E-box-binding homeobox (ZEB)1 and ZEB2 and their associations in breast cancer. The mRNA and protein expression of BCL6, ZEB1 and ZEB2 was assessed using in situ hybridization and immunohistochemistry, respectively, in 228 patients with breast cancer and 80 patients with benign breast disease. In addition, the association between BCL6, ZEB1 and ZEB2 expression and the clinicopathological characteristics and survival of patients with breast cancer were analyzed. The mRNA and protein expression of BCL6, ZEB1 and ZEB2 were significantly higher in breast cancer tissues compared with benign breast disease tissues (P<0.05). The expression of BCL6, ZEB1 and ZEB2 were significantly positively correlated with tumor size, lymph node metastasis and a higher tumor stage (P<0.05). Furthermore, patients with BCL6, ZEB1 and ZEB2 protein-positive primary tumors had significantly lower overall survival (P=0.001, 0.002 and 0.001, respectively) and relapse-free survival (P=0.002, 0.001 and 0.003, respectively) rates. The mRNA expressions of ZEB1 (r_s=0.326, P<0.001) and ZEB2 (r_s=0.382, P<0.001) were significantly positively correlated with BCL6 mRNA expression, and the protein expressions of ZEB1 ((r_s=0.449, P<0.001) and ZEB2 (r_s=0.669, P<0.001) were significantly positively correlated with BCL6 protein expression. These results suggest that BCL6, ZEB1 and ZEB2 are potential biomarkers for the invasion, metastasis and prognosis of breast cancer, and that BCL6 may be a regulator of the ZEB family.

Keywords: B-cell lymphoma 6; breast neoplasm; immunohistochemistry; in situ hybridization; zinc finger E-box-binding homeobox family.

Figure 1.

mRNA and protein expression of BCL6, ZEB1 and ZEB2 in breast cancer tissue specimens. In situ hybridization analysis of (A) BCL6, (B) ZEB1 and (C) ZEB2 mRNA in an invasive ductal carcinoma. Immunohistochemical staining of (D) BCL6, (E) ZEB1 and (F) ZEB2 protein in an invasive ductal carcinoma. Magnification, ×400. BCL6, B-cell lymphoma 6; ZEB, zinc finger E-box-binding homeobox.

Figure 2.

Association between BCL6, ZEB1 and ZEB2 protein expression and the survival of patients with breast cancer. Association between (A) BCL6, (B) ZEB1 and (C) ZEB2 protein expression and RFS and OS. BCL6, B-cell lymphoma 6; ZEB, zinc finger E-box-binding homeobox; RFS, relapse-free survival; OS, overall survival.