Detection The Relationship Between Expression Of Cell Cycle-related Protein And P53, Clinicalpathological Characteristics And Prognostic Significance In ER/PR-negative Breast Cancer

Objectives:Investigate the expression of ZWINT protein, CYCLIN D1, CYCLIN B2,p53and their correlation with the clinicalpathological features and prognosis of ER/PR-negative breast cancer.Methods:315ER/PR-negative breast cancer surgical cases collected from January1999to December2006were included in this study with detailed clinical, pathological and follow-up information.99cases that fit this research were included in the study. We set the44cases that died within five years as the case group, and55cases that survived for more than8years as the control group. Immunohistochemistry (IHC) analysis was performed on tissue microarrays (TMAs) that were made from all cases to analyze the expression of molecular markers including ZWINT, CYCLIN D1, CYCLIN B2and p53antibodies. The expression of the molecular markers, clinical characteristics and biological behaviors were analyzed in order to identify prognosis factors in ER/PR-negative breast cancer.Results:ZWINT expression in breast cancer tissues is located in the nucleus. The expression rates were87.9%[high expression in eight cases (8.1%), low expression in79cases (79.8%)], and12.1%negative. The expression rates in ER/PR-negative breast cancer were consistently higher than those in the tumor-adjacentnon-malignant tissues; The expression of CYCLIN D1is also located nucleus, the expression rates were88.8%[high expression of19(19.4%), low expression of68(69.4%)], and11.2%negative, The expression rates in ER/PR-negative breast cancer were consistently higher than those in the tumor-adjacentnon-malignant tissues. CYCLIN B2expresses mainly in the cytoplasm and partially locates in the membrane. The expression rates were high expression in23cases (23.2%) and low expression of76patients (76.8%). The expression of p53is located in the nucleus. The expression rates were64.6%positive and36.1%negative.ZWINT protein in the case group and control group of high expression rates showed significant difference (P<0.05), and was associated with poor prognosis (r=0.307, P <0.05). ZWINT protein’s high expression rates showed significant difference (P<0.05) between HER-2over-expression group and triple-negative group, which was associated with HER-2overexpression (r=0.220, P<0.05).The CYCLIN D1expression was significantly higher in the HER-2over-expression group than in triple-negative (ER-, PR-, HER-2-) breast cancer group (P<0.05), and was associated with HER-2overexpression (r=0.218, P<0.05). The CYCLIN D1high expression in the case group and the control group showed significant difference (P <0.05). CYCLIN Dl’s high expression in lymph-node metastasis and no-lymph-node metastasis showed significant difference (P<0.05). Its expression and lymph node metastasis are positively correlated (r=0.297, P<0.05).The CYCLIN B2expression in the case group and the control group showed insignificant difference (P>0.05). CYCLIN B2protein expression of HER-2positive breast cancer group rate was significantly higher than the triple negative breast cancer group (15.8%vs3.4%, P＜0.05), and was associated with the HER-2gene amplification (r=0.297,P<0.05).p53’s expression did not show a significant effect in either the case group or the control group (P>0.05).Clinical stage showed significant differences.(I:9.1%vs20.0%; Ⅱ:38.6%vs61.8%; Ⅲ:52.3%vs18.2%), and was negatively associated with prognosisUnivariate analysis showed high ZWINT protein expression level, high CYCLIN D1expression level, and clinical stage and lymph node metastasis had significant influences on ER/PR-negative breast cancer patients (P<0.05).Multivariate analysis showed high ZWINT protein expression level and axillary lymph node metastasis was an independent prognostic factor. Conclusion:1. High expression of ZWINT protein in ER/PR-negative breast cancer was associated with poor prognosis, and was related with HER-2overexpression. It might be an independence prognostic factor.2. Expression of CYCLIN D1was associated with HER-2overexpression and the high expression of CYCLIN D1was related with poor prognosis. The high expression of CYCLIN D1was correlated with lymph node metastasis.3. The CYCLIN B2high expression was associated with HER-2overexpression.4. Axillary lymph node metastasis was an independent prognostic factor.5. Clinical stage had significant influence on ER/PR-negative breast cancer patients.