摘要
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 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.
出处
《中华肿瘤防治杂志》
CAS
北大核心
2014年第11期836-840,共5页
Chinese Journal of Cancer Prevention and Treatment
基金
国家自然科学基金重点项目(30930038)
国家自然科学基金(81302292)
