Division of Diagnostic Pathology, National Cancer Center Hospital, Tokyo, Japan.
Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan.
Br J Cancer. 2023 Oct;129(7):1176-1183. doi: 10.1038/s41416-023-02382-z. Epub 2023 Aug 5.
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.
本研究旨在阐明 HER2 扩增和低表达结直肠癌（CRC）的临床病理和分子特征。我们还对 CRC 中的 HER2 表达状态进行了特征分析，重点关注其肿瘤内异质性和转移灶的改变，以建立实用的 HER2 状态评估。
我们通过免疫组织化学和 FISH 分别评估了 1009 例 CRC 中的 HER2 表达和 HER2 扩增情况，并将结果与临床病理和分子数据相关联。对于 HER2 阳性肿瘤，还评估了转移灶中的 HER2 表达情况。
鉴定出 25 例 HER2 扩增（2.5%）和 46 例 HER2 低表达肿瘤（4.6%）。HER2 扩增肿瘤始终缺乏黏液成分，而 HER2 低表达肿瘤倾向于位于右结肠，但没有其他临床病理特征。仅在 2 例 HER2 扩增肿瘤（8%）中检测到 KRAS、NRAS 或 BRAF 突变，而 23 例 HER2 低表达肿瘤（50%）中有 1 种突变。大多数 HER2 扩增和 HER2 低表达肿瘤显示出均匀或镶嵌型 HER2 表达模式，簇状异质性表达模式较为罕见。在 HER2 扩增（93%）和 HER2 低表达肿瘤（81%）中，大多数转移灶中 HER2 表达得以维持。
这些结果表明，基于活检的原发灶评估适用于确定有资格接受系统 HER2 靶向治疗的 CRC 患者。
