| Background:Breast cancer is characterized by genetic heterogeneity, encompassing different tumor types with distinct biologic features and clinical behaviors. Traditional clinicopathologic factors, such as tumor size, patient age, lymph node status, and hormone receptor status do not fully account for the disease's biologic complexity. Breast cancer was recently classified into subtypes according to gene expression profiles, which are characterized by distinct clinical and pathological features and respond in an accordingly distinct manner to chemotherapy. Additional molecular markers are being sought to further refine breast cancer classification. Because gene array technology is expensive and not widely available, several groups have aimed to use immunohistochemical approaches to identify a prognostic biomarker and construct algorasims to subclassfy breast cancer with comparable differences in clinical behavior and outcome in clinical practice. Jacquemier et al detected the expression of 21 proteins including ER, PR, HER2å’ŒCK5/6 to subclassfy breast cancer with different prognosis. Additional molecular markers are being sought to further refine breast cancer classification. Recent global gene expression studies have shown that high FOXA1 mRNA expression is associated with ER expression and is constantly present in luminal A tumors, a subset of ER-positive tumors with a favorable outcome. This study collected 162 invasive breast cancer of Huashan hospital, including 128 infiltrative ductal carcinoma. The expression of ER,PR,HER2 and CK5/6 was examed, and these samples were conducted immunohistochemical intrinsic breast cancer subtypes as luminal A (ER+ and/or PR+ and HER2-), luminal B (ER+ and/or PR+ and HER2+), HER2+(ER-and PR-and HER2+), basal-like (ER-and PR-, HER2-, and CK5/6+), and unclassified (ER- and PR-, HER2-, and CK5/6-). In this retrospective study, we performed an immunohistochemical analysis to determine FOXA1 protein expression in a well-characterized series of unselected breast cancer patients who had undergone long-term follow-up and to assess its prognostic significance. Methods:One hundred and sixty two cases of infiltrative breast cancer diagnosed by Huashan Hospital were studied by using immunohistochemical staining with an antibody panel of ER, PR, HER2, CK5/6, GATA-3 and FOXA1 and subclassified referring to previous reports.Result:The expression of ER, PR, HER2 and CK5/6 was detected in 67%,45%,27% and 27% cases, respectively. All cases were subclassified into five subgroups, with luminal A 55%, luminal B 20%, HER2+ 7%, basal-like 10% and unclassied cases 8%. It was demonstrated that the luminal A group was associated with the best prognosis but the basal-like group worst by univariate analysis. Multivariate analysis demonstrated that both the clinical stage and immunohistochemical subtypes of tumor were related to overall survival. Menses status were different among these subtypes. Fifty-four percent of tumors had nuclear expression of FOXA1 (H-score=10). FOXA1 expression was associated with small primary tumor size (p=0.028), no lymph node metastasis (p=0.044)and low clinical stage (p=0.001). An association was found between FOXA1 expression and long overall survival duration (log rank= 4.808, p=0.028). Overall survival durations among the subtypes were significantly different (Log-rank= 30.421, p<0.001); patients with the luminal A subtype had longer survival durations than did those with other subtypes. FOXA1 expression was not an independent predictor of survival (p=0.578).Conclusion:According to the expression of ER, PR, HER2 and CK5/6, the breast cancer could be subclassified into five subgroups with different biological features and outcome, having a role in evaluating the prognosis and guiding the clinical treatment. FOXA1 may be a new biomarkers of luminal A subtypes. The prognostic ability of FOXA1 in low-risk breast cancers may be useful in treatment decision-making. |
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