Department of Pathology, Yeungnam University College of Medicine, Daegu, Korea.
J Breast Cancer. 2012 Mar;15(1):24-33. doi: 10.4048/jbc.2012.15.1.24. Epub 2012 Mar 28.
This study aimed to investigate the clinical significance of chromosome 17 centromere (CEP17) multiplication (increased copy number of CEP17) related to human epidermal growth factor receptor 2 (HER2) and topoisomerase II alpha (TOP2A) status in patients with invasive breast cancer.
We constructed tissue microarrays using 594 invasive breast cancer samples and performed single-color silver-enhanced in situ hybridization (SISH) assay for HER2, TOP2A, and CEP17 to assess for copy number aberrations. The association of CEP17 multiplication with patient survival was analyzed according to HER2 and TOP2A status.
Among 567 informative cases, HER2 amplification was noted in 22.8%, TOP2A amplification in 8.3% and TOP2A deletion in 11.1%. CEP17 multiplication was identified in 33.2% and was significantly associated with worse overall survival (OS) (p=0.02) and disease-free survival (DFS) (p=0.02). CEP17 multiplication correlated with patient survival in patients with normal TOP2A or non-amplified HER2 status, but the prognostic significance was lost in those with altered TOP2A or amplified HER2. On multivariate analyses, CEP17 multiplication was an independent prognostic factor for poorer OS (p=0.02) and DFS (p=0.01) in patients with normal TOP2A and non-amplified HER2.
CEP17 multiplication was identified as a promising prognostic marker in patients with invasive breast cancer exhibiting either non-amplified HER2 or normal TOP2A status.
本研究旨在探讨人类表皮生长因子受体 2（HER2）和拓扑异构酶 IIα（TOP2A）状态相关的染色体 17 着丝粒（CEP17）倍增（CEP17 拷贝数增加）在浸润性乳腺癌患者中的临床意义。
我们使用 594 例浸润性乳腺癌样本构建组织微阵列，并进行 HER2、TOP2A 和 CEP17 的单探针银增强原位杂交（SISH）检测，以评估拷贝数异常。根据 HER2 和 TOP2A 状态分析 CEP17 倍增与患者生存的关系。
在 567 例信息丰富的病例中，HER2 扩增率为 22.8%，TOP2A 扩增率为 8.3%，TOP2A 缺失率为 11.1%。确定 CEP17 倍增率为 33.2%，与总生存（OS）（p=0.02）和无病生存（DFS）（p=0.02）显著相关。CEP17 倍增与正常 TOP2A 或非扩增 HER2 状态的患者生存相关，但在 TOP2A 改变或 HER2 扩增的患者中，其预后意义丧失。多变量分析显示，CEP17 倍增是正常 TOP2A 和非扩增 HER2 患者 OS（p=0.02）和 DFS（p=0.01）较差的独立预后因素。
CEP17 倍增被确定为具有非扩增 HER2 或正常 TOP2A 状态的浸润性乳腺癌患者有前途的预后标志物。
