Department of Pathology, Radboud university medical center (Radboudumc), Nijmegen, The Netherlands.
Department of Tumor Immunology, Radboud university medical center (Radboudumc), Nijmegen, The Netherlands.
Sci Rep. 2019 Aug 12;9(1):11679. doi: 10.1038/s41598-019-48212-2.
Breast cancer treatment depends on human epidermal growth factor receptor-2 (HER2) status, which is often determined using dual probe fluorescence in situ hybridisation (FISH). Hereby, also loss and gain of the centromere of chromosome 17 (CEP17) can be observed (HER2 is located on chromosome 17). CEP17 gain can lead to difficulty in interpretation of HER2 status, since this might represent true polysomy. With this study we investigated whether isolated polysomy is present and how this effects HER2 status in six breast cancer cell lines and 97 breast cancer cases, using HER2 FISH and immunohistochemistry, DNA ploidy assessment and multiplex ligation dependent probe amplification. We observed no isolated polysomy of chromosome 17 in any cell line. However, FISH analysis did show CEP17 gain in five of six cell lines, which reflected gains of the whole chromosome in metaphase spreads and aneuploidy with gain of multiple chromosomes in all these cases. In patients' samples, gain of CEP17 indeed correlated with aneuploidy of the tumour (91.1%; p < 0.001). Our results indicate that CEP17 gain is not due to isolated polysomy, but rather due to widespread aneuploidy with gain of multiple chromosomes. As aneuploidy is associated with poor clinical outcome, irrespective of tumour grade, this could improve future therapeutic decision making.
乳腺癌的治疗取决于人表皮生长因子受体 2（HER2）的状态，通常使用双探针荧光原位杂交（FISH）来确定。通过这种方法，还可以观察到 17 号染色体着丝粒（CEP17）的丢失和获得（HER2 位于 17 号染色体上）。CEP17 的获得可能导致 HER2 状态的解读困难，因为这可能代表真正的三体。通过这项研究，我们使用 HER2 FISH 和免疫组织化学、DNA 倍性评估和多重连接依赖探针扩增，在 6 种乳腺癌细胞系和 97 例乳腺癌病例中，调查了孤立性三体是否存在以及其对 HER2 状态的影响。我们在任何细胞系中都没有观察到 17 号染色体的孤立性三体。然而，FISH 分析确实显示在 6 种细胞系中的 5 种存在 CEP17 获得，这反映了在中期分裂中整条染色体的获得以及在所有这些情况下的染色体非整倍性和多个染色体的获得。在患者样本中，CEP17 的获得确实与肿瘤的非整倍体相关（91.1%；p<0.001）。我们的结果表明，CEP17 的获得不是由于孤立性三体，而是由于广泛的染色体非整倍性和多个染色体的获得。由于非整倍体与不良的临床结果相关，无论肿瘤分级如何，这都可能改善未来的治疗决策。
