Gastric and gastroesophageal junction adenocarcinomas (GA/GEJA) are associated with a poor prognosis, primarily due to late disease diagnosis. Human Epidermal Growth Factor Receptor 2 (HER2) overexpression and programmed death-ligand 1 (PD-L1) expression are important biomarkers for treatment selection in locally advanced unresectable and metastatic GA/GEJA, and there is increasing interest in their role in earlier stages of disease. In this study, we aimed to evaluate HER2 and PD-L1 expression in a curative-intent GA/GEJA cohort to describe their expression patterns and analyze the association between HER2 expression and clinicopathological features. HER2 expression was evaluated in surgical and endoscopic submucosal dissection tumor samples, and PD-L1 was evaluated in HER2-positive cases. The clinical cohort included 107 patients, with 8.4% testing positive for HER2 (seven of whom also exhibited a PD-L1 combined positive score of ≥1. HER2 status was not significantly associated with survival outcomes. A pathologist-guided, region-specific analysis revealed that PD-L1 expression rarely overlaps with HER2-positive tumor areas. While the therapeutic implications of these observations remain unknown, these findings suggest that combination strategies targeting HER2 and PD-L1 might be directed toward distinct tumor subclones. The herein disclosed region-specific biomarker expression patterns may have important therapeutic and prognostic impacts, warranting further evaluation.
胃及胃食管结合部腺癌（GA/GEJA）预后较差，主要归因于疾病诊断较晚。人表皮生长因子受体2（HER2）过表达与程序性死亡配体1（PD-L1）表达是局部晚期不可切除及转移性GA/GEJA治疗选择的重要生物标志物，其在疾病更早期阶段的作用日益受到关注。本研究旨在评估根治性治疗GA/GEJA队列中HER2与PD-L1的表达情况，描述其表达模式并分析HER2表达与临床病理特征间的关联。通过手术及内镜黏膜下剥离术获取的肿瘤样本评估HER2表达，并在HER2阳性病例中评估PD-L1表达。临床队列共纳入107例患者，其中8.4%呈HER2阳性（其中7例同时显示PD-L1综合阳性评分≥1）。HER2状态与生存结局无显著相关性。病理医师指导的区域特异性分析显示，PD-L1表达极少与HER2阳性肿瘤区域重叠。尽管这些观察结果的治疗意义尚未明确，但本研究表明针对HER2与PD-L1的联合治疗策略可能作用于不同的肿瘤亚克隆。本文揭示的区域特异性生物标志物表达模式可能具有重要的治疗及预后价值，值得进一步深入研究。
肿瘤(癌症)患者之家