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目的:研究细胞分裂周期蛋白6(cell division cycle 6,CDC6)在乳腺癌组织中的表达与人类表皮生长因子受体2(HER2/neu)基因扩增、临床病理学特征及预后的相关性。方法:收集2013-01-01-2013-03-31天津医科大学肿瘤医院乳腺病理研究室进行HER2/neu FISH检测的原发性乳腺癌蜡块标本120例和2005-01-01-2005-04-30有临床随访资料的乳腺癌标本195例,并选取同期30例乳腺小叶增生病例作为良性对照。采用免疫组织化学染色法(IHC)检测癌组织中CDC6的表达情况并分析其与HER2/neu基因扩增和临床病理学特征及术后随访资料的相关性。结果:120例IDC-NOS标本中,CDC6阴性表达25例(20.8%),阳性表达95例(79.2%);CDC6阴性表达组HER2/neu基因扩增12例(48.0%),CDC6阳性表达组HER2/neu基因扩增74例(77.9%)。CDC6表达与HER2/neu基因扩增呈明显正相关,r=0.242,P=0.008。乳腺癌组织中CDC6阳性表达率为77.4%(151/195),明显高于乳腺小叶增生组织的60.0%(18/30),差异有统计学意义,z=-2.052,P=0.040。CDC6表达与肿瘤大小(P=0.025)、组织学分级(P=0.021)、pTNM分期(P=0.023)、HER2/neu表达水平(P=0.022)和Ki-67表达水平(P=0.003)均呈正相关。CDC6的表达与乳腺癌患者的累计无病生存(cumulative disease-free survival,DFS)时间呈负相关,P=0.020。结论:CDC6是与HER2/neu基因扩增和蛋白表达正相关的蛋白,其表达与乳腺癌细胞增殖有关,并且提示预后不良,有望成为乳腺癌治疗的新靶点。
Objective: To study the correlation between the expression of cell division cycle 6 (CDC6) in breast cancer and the amplification of HER2 / neu gene, clinicopathological features and prognosis. Methods: Totally 120 cases of primary breast cancer wax samples were detected by HER2 / neu FISH in the Department of Breast Pathology, Tumor Hospital of Tianjin Medical University from January to December in 2013-01-01-2013-03-31. -30 clinical follow-up information of breast cancer specimens 195 cases, and select the same period 30 cases of breast lobular hyperplasia as a benign control. Immunohistochemical staining (IHC) was used to detect the expression of CDC6 in cancerous tissue and its correlation with HER2 / neu gene amplification and clinicopathological characteristics and postoperative follow-up data were analyzed. RESULTS: Among 120 IDC-NOS specimens, 25 (20.8%) were CDC6 negative and 95 (79.2%) were positive for CDC6, 12 (48.0%) were positive for CDC6 negative, while CDC6 positive HER2 / neu gene amplification in 74 cases (77.9%). The expression of CDC6 was positively correlated with the amplification of HER2 / neu gene, r = 0.242, P = 0.008. The positive rate of CDC6 expression in breast cancer tissues was 77.4% (151/195), which was significantly higher than that in breast lobular hyperplasia tissues (60.0%, 18/30). The difference was statistically significant (z = -2.052, P = 0.040). The expression of CDC6 was significantly correlated with tumor size (P = 0.025), histological grade (P = 0.021), pTNM stage (P = 0.023), HER2 / neu expression (P = 0.022) and Ki- Was positively correlated. The expression of CDC6 was negatively correlated with the cumulative disease-free survival (DFS) of breast cancer patients, P = 0.020. Conclusion: CDC6 is a positive correlation with HER2 / neu gene amplification and protein expression. The expression of CDC6 is correlated with the proliferation of breast cancer cells, and suggests that the prognosis is poor. CDC6 is expected to become a new target for the treatment of breast cancer.