Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.
Department of Molecular Diagnostics, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.
Oncologist. 2021 Jul;26(7):e1161-e1170. doi: 10.1002/onco.13786. Epub 2021 May 4.
The impact of HER2 somatic mutations in colorectal carcinoma (CRC) has not been well studied and its relationship with microsatellite instability-high (MSI-H) is yet to be fully elucidated.
From February 2017 to February 2020, the data of patients with CRC who underwent next-generation sequencing and had detailed record of clinicopathological information were investigated. HER2 alteration and its relationship with MSI-H were analyzed.
Among 731 patients who underwent sequencing, 55 patients (7.5%) had HER2 alteration, including 29 (4.0%) with HER2 somatic mutations, 24 (3.3%) with HER2 gene amplification, and 2 patients (0.2%) with both HER2 mutations and amplification. R678Q was the most common mutated kinase domain, and no HER2 kinase domain in-frame insertions/deletions were found in HER2 mutated cases. MSI-H was found in 5.2% of our cohort and 36.8% of MSI-H patients had HER2 mutation. For HER2 mutated cases, 48.3% were MSI-H, whereas none of the HER2 amplification cases were MSI-H. MSI-H patients with HER2 mutation had significantly worse median progression-free survival for programmed death-1 (PD-1) antibody than those without HER2 alteration (p = .036).
High MSI-H rate was found in HER2 mutated cases, but no MSI-H was found in HER2 amplification cases. MSI-H patients with HER2 mutated had worse progression-free survival for PD-1 antibody than those without.
This study highlights the high microsatellite instability-high (MSI-H) rate in HER2 mutated cases but no MSI-H in HER2 amplification cases. Moreover MSI-H patients with HER2 mutated had worse progression-free survival for programmed death-1 antibody than those without. Further research to explore the internal relationship between HER2 alteration and MSI-H is needed.
HER2 体细胞突变在结直肠癌（CRC）中的影响尚未得到充分研究，其与微卫星不稳定高（MSI-H）的关系尚未完全阐明。
本研究回顾性分析了 2017 年 2 月至 2020 年 2 月间行下一代测序且有详细临床病理资料记录的 CRC 患者，分析了 HER2 改变及其与 MSI-H 的关系。
在 731 例接受测序的患者中，有 55 例（7.5%）存在 HER2 改变，包括 29 例（4.0%）HER2 体细胞突变，24 例（3.3%）HER2 基因扩增，2 例（0.2%）同时存在 HER2 突变和扩增。R678Q 是最常见的突变激酶域，在 HER2 突变病例中未发现 HER2 激酶域框内插入/缺失。本队列中 MSI-H 发生率为 5.2%，其中 36.8%的 MSI-H 患者存在 HER2 突变。在 HER2 突变病例中，48.3%为 MSI-H，而 HER2 扩增病例均为 MSS。MSI-H 患者中，HER2 突变患者的程序性死亡受体-1（PD-1）抗体无进展生存期明显差于无 HER2 改变者（p=0.036）。
HER2 突变病例中 MSI-H 发生率较高，但 HER2 扩增病例中未发现 MSI-H。HER2 突变的 MSI-H 患者 PD-1 抗体无进展生存期较无 HER2 改变者差。
本研究提示 HER2 突变病例中 MSI-H 发生率较高，但 HER2 扩增病例中未发现 MSI-H。此外，HER2 突变的 MSI-H 患者 PD-1 抗体无进展生存期较无 HER2 改变者差。需要进一步研究以探索 HER2 改变与 MSI-H 之间的内在关系。
