Expression Of FZD7and β-catenin In Different Subtypes Of Breast Cancer And Their Clinical Significance

Background and objective Breast cancer is the most common malignancy in women, with the constant improvement of the level of molecular biology techniques and diagnosis and treatment in recent years, the mortality rate is declining. However, the heterogeneity of breast cancer makes the efficiency of subtypes especially triple-negative breast cancer poor. Triple-negative breast cancer (TNBC) is a distinct subtype of breast cancer, which estrogen receptor (ER) and progesterone receptor (PR) and human epidermal growth factor2(Her2) were negative. It accounts for approximately15%～23%of breast cancer cases. Since the lack of targets of endocrine and anti-Her2therapy, there is no targeted treatment regimens.The canonical Wnt signaling transduction pathway, Wnt/β-catenin signaling pathway, plays a major role in tumorigenesis and progress. Some studies found that this pathway is activated in breast cancer. The transmembrane receptor FZD7bonds to Wnt protein, which initiate the Wnt/β-catenin signaling pathway. β-catenin, the core component of Wnt/β-catenin signaling pathway, is a multifunctional protein, which is the important member of signal transduction in Wnt/β-catenin signaling pathway, participating in the regulation of cell adhesion. The degradation in cytoplasm and accumulation in nucleus of β-catenin can activate transcription of a series of target genes such as C-myc and Cyclin-D1, which cause various diseases or even tumors. The regulation of β-catenin in the intracellular stability and its accumulation within the cells is one of the most critical events in Wnt/β-catenin pathway.Our research aims to investigate the expressions of FZD7and β-catenin in different subtypes of breast cancer, to research their relationship with clinicopathologic features and prognosis, and the relevance between FZD7and β-catenin, furthermore, to explore their significance in TNBC.Methods The expressions of FZD7and β-catenin was detected in38cases of TNBC,131cases of non-TNBC and10cases of paracarcinoma normal breast tissues by using tissue microarrays and immunohistochemistry. A retrospective analysis of clinicopathologic features and prognosis was Conducting SPSS18.0software was using for statistical analysis.x2test was used to compare the rate, survival analysis using the Kaplan-Meier method, the difference in survival compared using the Log-Rank test. Independent prognostic factors were analyzed using Cox regression model. P<0.05was considered statistically significant.Results FZD7protein was not only observed on normal breast tissues; however, FZD7protein was detected on the cytomembrane of breast cancer tissues. Besides, FZD7expression was higher in TNBC cases (65.8%,25/38) than in non-TNBC cases (41.2%,54/131). β-catenin protein was only observed on the cytomembrane of normal breast tissues; nevertheless, it was not only observed on the cytomembrane of breast cancer tissues, but also in the cytoplasm and nucleus. Abnomal β-catenin expression was higher in TNBC cases (78.9%,30/38) than in non-TNBC cases (60.3%,79/131). The difference was statistically significant (x2=4.47, P<0.05). FZD7overexpression is related to abnormal β-catenin expression (P<0.05). In TNBC, FZD7overexpression is associated with the lymph node status, high tumor grade and Ki67-positive (P<0.05), however, there is no relationship with the age, tumor size, TNM stage and P53status (P>0.05). In non-TNBC, FZD7overexpression is only associated with the lymph node status (P<0.05), however, there is no association with the age, tumor size, high tumor grade, TNM stage, Ki67status and P53status was shown (P>0.05). An association was identified between abnormal β-catenin expression and lymph node status, high tumor grade, TNM stage and Ki67-positive (P<0.05). Nevertheless, there is no association between abnormal β-catenin expression and the age, tumor size and P53status (P>0.05). No significant correlation was found between abnormal β-catenin expression and the clinicopathologic features in TNBC (P>0.05). FZD7overexpression and abnormal β-catenin expression is related with prognosis in breast cancer, which is independent prognostic factor. But, there is no significant correlation was found between abnormal β-catenin expression and prognosis in TNBC (P>0.05).Conclusion Wnt/β-catenin signaling pathway is activated in breast cancer, and the probability in TNBC is more than in non-TNBC. FZD7and β-catenin may play an important role in breast cancer tumorigenesis and progress. FZD7and β-catenin could be used as a new indicator for biological behavior, prognosis and targeted therapy in breast cancer hopefully. However, whether it can be served as specific indicator of prognosis in TNBC and its relation with TNBC remain to do further research by expanding sample.