Department of Respiratory Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Xinkai Road, Dongcheng, Beijing, China.
Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Xinkai Road, Dongcheng, Beijing, China.
Interdiscip Sci. 2019 Jun;11(2):258-265. doi: 10.1007/s12539-019-00329-8. Epub 2019 May 11.
PD-1/PD-L1 inhibitors is the important drugs of immunotherapy for malignant tumors. PD-L1 expression is an important biomarker of selecting patients for ICIs therapy. However, the correlation of PD-L1 expression with clinicopathologic features in lung adenocarcinoma remains controversial.
PD-L1 expression was tested using clone SP263 by immunohistochemistry (IHC) on Ventana automated Benchmark in tissue micro-arrays (TMA) in lung adenocarcinoma. The association of PD-L1 expression with clinicopathologic characteristics, including gender, age, histological subtype, smoking history, stage, and genotype were analyzed.
404 patients were available for analyzing. The incidence of PD-L1 expression was 22.5% (using a cutoff of ≥ 25%). Statistical analysis showed PD-L1 expression was associated with advanced stage, lymph node (LN) metastasis, solid predominant subtype and wild-type epidermal growth factor receptor (EGFR) gene. In subgroup analysis, PD-L1 expression in patients with EGFR exon 19 deletions was higher than that of with EGFR L858R mutation at exon 21 (21.6% vs. 10.2%, P = 0.046). In multivariate analysis for overall survival (OS) by Cox hazard proportion model, patients with EGFR gene mutations (HR 1.635, 95% CI 1.310-2.040, P < 0.001) and early stage (HR 2.495, 95% CI 2.003-3.106, P < 0.001) had a longer survival, while PD-L1 expression was not associated with overall survival (HR 0.847, 95% CI 0.655-1.094, P = 0.203).
For patients with lung adenocarcinoma, LN metastasis, wild-type EGFR, advanced stage, solid predominant subtype were independent predictors of PD-L1 expression by multivariate analysis. PD-L1 expression may be not a predictor of OS for patients with lung adenocarcinoma.
PD-1/PD-L1 抑制剂是恶性肿瘤免疫治疗的重要药物。PD-L1 表达是选择免疫检查点抑制剂（ICI）治疗患者的重要生物标志物。然而，PD-L1 表达与肺腺癌的临床病理特征之间的相关性仍存在争议。
使用免疫组织化学（IHC）检测 PD-L1 表达，在组织微阵列（TMA）上使用克隆 SP263 对肺腺癌进行检测。分析 PD-L1 表达与临床病理特征的相关性，包括性别、年龄、组织学亚型、吸烟史、分期和基因型。
共 404 例患者可进行分析。PD-L1 表达的发生率为 22.5%（采用≥25%的截断值）。统计学分析显示，PD-L1 表达与晚期、淋巴结（LN）转移、实性为主型和野生型表皮生长因子受体（EGFR）基因有关。在亚组分析中，EGFR 外显子 19 缺失患者的 PD-L1 表达高于 EGFR 外显子 21 L858R 突变患者（21.6%比 10.2%，P=0.046）。多因素 Cox 风险比例模型分析总生存期（OS），EGFR 基因突变患者（HR 1.635，95%CI 1.310-2.040，P<0.001）和早期患者（HR 2.495，95%CI 2.003-3.106，P<0.001）的生存期较长，而 PD-L1 表达与总生存期无关（HR 0.847，95%CI 0.655-1.094，P=0.203）。
对于肺腺癌患者，LN 转移、野生型 EGFR、晚期、实性为主型是多因素分析 PD-L1 表达的独立预测因子。PD-L1 表达可能不是肺腺癌患者 OS 的预测因子。
