乳腺癌组织CDC6表达及其临床意义的研究

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／neuFISH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）、pT-NM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。

Expression and significance of CDC6 in breast cancer tissues

OBJECTIVE：To determine the expression of cell division cycle 6（CDC6） in breast cancer（BC） and inves- tigate its relationship to HER-2/neu gene amplification and clinical significance. METHODS： Totally 315 primary BC cases diagnosed in Tianjin Medical University Cancer Institute and Hospital were selected in this study,including 120 cases with HER-2/neu FISH results from January 1 to March 31 of 2013 and 195 cases with long-term follow-up（30 lobular hyperplasia cases during the same time were selected as control group） from January 1 to April 30 of 2005. The expressions of CDC6 were detected by immunohistochemistry（IHC）. We analyzed relationship of CDC6 expression to HER-2/neu gene amplification and its effect on c!inicopathological characteristics and prognosis for BC patients. RESULTS： In 120 IDC NOS cases,25 cases（20. 8%） had CDC6 negative expression and 95 cases（79. 2%） had CDC6 positive expression; In CDC6 negative and positive groups,12 cases（48.0%） and 74 cases（77.9%） had HER2/neu gene amplification. CDC6 was positively correlated with HER2/neu gene amplification （rs= 0. 242, P=0. 008）. Among 22.6% （44/195） and 77. 4% （152/195） of cases,CDC6 had negative and positive expressions respectively. The rate of positive expression of CDC6 in BC cases was significantly higher than that in Lobular hyperplasia cases（60.0%, P=0. 040）. CDC6 expression was found to be associated with unfavorable features of BC patients, including tumor size（P = 0. 025）, histological grade（P = 0. 021）, pTNM stage （P=0. 023）, HER2/neu expression （P=0. 022） and Ki-67 expression （P=0. 003）. The expression of CDC6 was negatively correlated with disease-free survival （DFS） time （P=0. 020）. CONCLUSIONS： CDC6 is a protein associated with HER2/neu amplification and expression,its expression is related to cell proliferation and poor prognosis in BC patients. Therefore CDC6 is expected to become a new target for breast cancer therapy.