本研究旨在阐明HER2扩增和HER2低表达结直肠癌（CRC）的临床病理和分子特征。我们还评估了CRC中HER2表达状态，重点关注肿瘤内异质性和转移性病灶中的HER2改变，以建立实用的HER2状况评估方法。我们通过免疫组化和FISH分析评估了1009例CRC的HER2表达和HER2扩增，并将结果与临床病理和分子数据进行相关性分析。对于HER2阳性肿瘤，还评估了转移性病灶中的HER2表达情况。共鉴定出25例HER2扩增肿瘤（2.5%）和46例HER2低表达肿瘤（4.6%）。HER2扩增肿瘤始终缺乏粘液成分，HER2低表达肿瘤倾向于位于右侧结肠，但其他临床病理特征未见。仅有2例HER2扩增肿瘤（8%）检测到KRAS、NRAS或BRAF突变，而23例HER2低表达肿瘤（50%）中有一种突变。大多数HER2扩增和HER2低表达肿瘤显示出均一或镶嵌的HER2表达模式，群集异质表达模式相对较少见。HER2表达在HER2扩增肿瘤（93%）和HER2低表达肿瘤（81%）的大多数转移性病灶中保持。这些结果表明，基于活检的原发病灶评估适用于识别适合系统HER2靶向治疗的CRC患者。© 2023该作者(们)，独家授权给Springer Nature Limited。

This study aimed to elucidate the clinicopathological and molecular features of HER2-amplified and HER2-low colorectal cancers (CRCs). We also characterised HER2 expression statuses in CRCs focusing on their intratumoral heterogeneity and alterations in metastatic lesions to establish practical HER2 status assessment.We evaluated 1009 CRCs for HER2 expression and HER2 amplification by immunohistochemistry and FISH, respectively, and correlated the results to clinicopathological and molecular data. For HER2-positive tumours, HER2 expression in metastatic lesions was also assessed.Twenty-five HER2-amplified (2.5%) and 46 HER2-low tumours (4.6%) were identified. HER2-amplified tumours consistently lacked a mucinous component and HER2-low tumours tended to be in the right colon, but no other clinicopathological features were noted. KRAS, NRAS or BRAF mutations were detected in only two HER2-amplified tumours (8%), whereas 23 HER2-low tumours (50%) had one of these mutations. Most HER2-amplified and HER2-low tumours showed a homogeneous or mosaic HER2 expression pattern and a clustered heterogeneous expression pattern was rather rare. HER2 expression was maintained in most metastatic lesions in both HER2-amplified (93%) and HER2-low tumours (81%).These results suggest that biopsy-based assessment of primary lesions is appropriate for the identification of CRC patients eligible for systemic HER2-targeted therapy.© 2023. The Author(s), under exclusive licence to Springer Nature Limited.