Breast Cancer Res Treat. 2010 Feb;120(1):1-7. doi: 10.1007/s10549-009-0539-2. Epub 2009 Sep 18.
Amplification of the HER2 gene, present in 15-30% of breast carcinomas, correlates with poor outcome and is an indication for treatment with trastuzumab. Standard testing methods for HER2 amplification are fluorescence (FISH) or chromogenic in situ hybridization (CISH). In FISH/CISH scoring, correction for chromosome 17 polysomy is believed to be critical for determination of true HER2 amplification as opposed to increased chromosome 17 copy number. The term "polysomy 17" is widely used and defined as > or =3 copies of the chromosome 17 centromere (probe CEP17, D17Z1). Thus, the centromere is assumed to be representative for the entire chromosome. This study aimed to investigate the frequency of polysomy 17 and its association with HER2 amplification in 111 invasive breast cancer patients by CEP17 CISH and by copy number analysis of a set of 17 genes along chromosome 17 using multiplex ligation-dependent probe amplification (MLPA).Chromosome 17 usually showed a complex pattern of gains and losses by MLPA, unrelated to the copy number status of the centromere. Increase in centromere 17 copy number (denoted "polysomy 17"), as assessed by CEP17 CISH, was found in 19% of the patients. Of these patients, 60% also showed amplification of HER2 measured by MLPA. However, none of the 111 patients showed a true polysomy of chromosome 17 by MLPA. Only two patients (1.8%) had a possible gain of 17q. Amplification of 17p was not found in any of the patients, although a possible loss of 17p was found in one patient. In conclusion, this extensive analysis of amplicons along chromosome 17 shows that true polysomy of chromosome 17, either of the whole chromosome or of the short or the long arm, is very rare in invasive breast cancer. Abnormal CEP17 copy numbers may therefore actually stem from high level gains or amplification of CEP17 regardless of copy number gains of the short and long arms of chromosome 17 and, at least in some cases, correction with CEP17 probes may provide misleading HER2 gene status assessment results.
HER2 基因扩增存在于 15-30%的乳腺癌中，与不良预后相关，是曲妥珠单抗治疗的指征。HER2 扩增的标准检测方法是荧光原位杂交（FISH）或显色原位杂交（CISH）。在 FISH/CISH 评分中，认为染色体 17 三体的校正对于确定真正的 HER2 扩增而不是增加染色体 17 拷贝数至关重要。“染色体 17 三体”一词被广泛使用，定义为 >或=3 个染色体 17 着丝粒（探针 CEP17、D17Z1）。因此，着丝粒被认为代表整个染色体。本研究旨在通过 CEP17 CISH 检测和使用多重连接依赖性探针扩增（MLPA）对沿染色体 17 的一组 17 个基因的拷贝数分析，检测 111 例浸润性乳腺癌患者中染色体 17 三体的频率及其与 HER2 扩增的关系。MLPA 通常显示染色体 17 的增益和缺失的复杂模式，与着丝粒的拷贝数状态无关。通过 CEP17 CISH 评估，19%的患者发现着丝粒 17 拷贝数增加（表示“染色体 17 三体”）。其中，60%的患者还表现出通过 MLPA 测量的 HER2 扩增。然而，通过 MLPA 没有发现 111 例患者中有真正的染色体 17 三体。只有 2 例患者（1.8%）存在 17q 的可能增益。在任何患者中均未发现 17p 的扩增，尽管在 1 例患者中发现了 17p 的可能缺失。总之，本研究对染色体 17 上的扩增子进行了广泛分析，结果显示，浸润性乳腺癌中真正的染色体 17 三体，无论是整条染色体还是短臂或长臂，都非常罕见。异常的 CEP17 拷贝数可能实际上源于 CEP17 的高水平增益或扩增，而与染色体 17 短臂和长臂的拷贝数增益无关，至少在某些情况下，CEP17 探针的校正可能会提供误导性的 HER2 基因状态评估结果。
