PD-L1 免疫组化标志物在胃癌中的预后价值及其与 HER2 状态的相关性。
Prognostic Value of PD-L1 Immunohistochemical Marker in Gastric Carcinoma and Its Correlation with HER2 Status.
机构信息
Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
Department of Clinical Oncology and Nuclear medicine, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
出版信息
Asian Pac J Cancer Prev. 2022 Apr 1;23(4):1433-1444. doi: 10.31557/APJCP.2022.23.4.1433.
OBJECTIVE
Programmed death-ligand 1 (PD-L1) and human epidermal growth factor receptor 2 (HER2) are currently considered as prognostic markers and therapeutic targets in many human cancers. This study aims to evaluate immunohistochemical (IHC) expression of PD-L1 in gastric cancer (GC) and explore its prognostic role in terms of association with HER2 expression, different clinico-pathological variables, in particular density and cluster designation (CD)8 positivity in tumor infiltrating lymphocytes (TILs) and with patients' disease-free and overall survival (DFS, OS).
METHODS
This retrospective cohort study included 111 diagnosed primary GC patients who underwent surgical resection at the Gastrointestinal Surgery Center (GISC), Faculty of Medicine, Mansoura University, Egypt. After demographic, clinicopathological and survival data collection, histopathological evaluation was done for GC typing, staging and assessment of the histopathological prognostic parameters. IHC was performed for PD-L1, HER2 and CD8. PDL-1 was scored using the Combined Positive Score (CPS).
RESULTS
PD-L1 was expressed in 43.2% of GCs at a CPS cut-off value ≥ 1. PDL-1 positivity was significantly associated with high TILs and CD8+ TILs (p=0.008, 0.016 respectively), indicating its contribution to tumor microenvironment along with the TILs. Multivariate analysis spotted PD-L1 positivity as an independent prognostic predictor for shorter OS in GC (p=0.013), with a tendency toward shorter DFS. Only 9.9% GCs were HER2 positive (score +3) with no significant association with PD-L1.
CONCLUSION
PDL-1 is a promising prognostic and therapeutic target in GC that may direct the selection of patients for immunotherapy and checkpoint-blockade (pembrolizumab) therapy.
目的
程序性死亡配体 1（PD-L1）和人表皮生长因子受体 2（HER2）目前被认为是许多人类癌症的预后标志物和治疗靶点。本研究旨在评估胃癌（GC）中 PD-L1 的免疫组化（IHC）表达，并探讨其与 HER2 表达、不同临床病理变量的相关性，特别是肿瘤浸润淋巴细胞（TILs）中密度和簇指定（CD）8 阳性的预后作用，并与患者的无病生存和总生存（DFS、OS）相关。
方法
本回顾性队列研究纳入了 111 例在埃及曼苏拉大学医学院胃肠外科中心（GISC）接受手术切除的确诊原发性 GC 患者。收集人口统计学、临床病理和生存数据后，对 GC 进行组织病理学评估，包括分型、分期和评估组织病理学预后参数。对 PD-L1、HER2 和 CD8 进行免疫组化检测。PD-L1 采用联合阳性评分（CPS）进行评分。
结果
在 CPS 截断值≥1 的情况下，43.2%的 GC 表达 PD-L1。PD-L1 阳性与高 TILs 和 CD8+TILs 显著相关（p=0.008，0.016），表明其与 TILs 一起促进肿瘤微环境。多变量分析发现 PD-L1 阳性是 GC 患者 OS 较短的独立预后预测因子（p=0.013），DFS 也有缩短的趋势。只有 9.9%的 GC 为 HER2 阳性（评分+3），与 PD-L1 无显著相关性。
结论
PD-L1 是 GC 有前途的预后和治疗靶点，可能指导免疫治疗和检查点阻断（pembrolizumab）治疗患者的选择。
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