通过免疫组织化学评估的PD-L1蛋白表达对于接受手术切除的非小细胞肺癌患者，既无预后价值，也不能预测辅助化疗的获益情况。
PD-L1 protein expression assessed by immunohistochemistry is neither prognostic nor predictive of benefit from adjuvant chemotherapy in resected non-small cell lung cancer.
作者信息
Tsao M-S, Le Teuff G, Shepherd F A, Landais C, Hainaut P, Filipits M, Pirker R, Le Chevalier T, Graziano S, Kratze R, Soria J-C, Pignon J-P, Seymour L, Brambilla E
机构信息
Department of Pathology, University Health Network, Toronto, Ontario, Canada.
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
出版信息
Ann Oncol. 2017 Apr 1;28(4):882-889. doi: 10.1093/annonc/mdx003.
BACKGROUND
The expression of programmed death (PD) ligand 1 (PD-L1) protein expression assessed by immunohistochemistry (IHC) has been correlated with response and survival benefit from anti-PD-1/PD-L1 immune checkpoint inhibitor therapies in advanced non-small cell lung carcinoma (NSCLC). The efficacy of several agents appears correlated with PD-L1 expression. It remains controversial whether PD-L1 is prognostic in NSCLC. We assessed the prognostic value of PD-L1 IHC and its predictive role for adjuvant chemotherapy in early stage NSCLC.
PATIENTS AND METHODS
Tumor sections from three pivotal adjuvant chemotherapy trials (IALT, JBR.10, CALGB 9633) using the E1L3N antibody were studied in this pooled analysis. PD-L1 staining intensity and percentage in both tumor cells (TCs) and immune cells (ICs) were scored by two pathologists. The average or consensus PD-L1 expression levels across intensities and/or percent cells stained were correlated with clinicopathological and molecular features, patient survivals and potential benefit of adjuvant chemotherapy.
RESULTS
Results from 982 patients were available for analysis. Considering staining at any intensities for overall PD-L1 expression, 314 (32.0%), 204 (20.8%) and 141 (14.3%) tumor samples were positive for PD-L1 staining on TCs using cut-offs at ≥1%, ≥10% and ≥25%, respectively. For PD-L1 expressing ICs, 380 (38.7%), 308 (31.4%) and 148 (15.1%) were positive at ≥ 1%, ≥10% and 25% cut-offs, respectively. Positive PD-L1 was correlated with squamous histology, intense lymphocytic infiltrate, and KRAS but not with TP53 mutation. EGFR mutated tumors showed statistically non-significant lower PD-L1 expression. PD-L1 expression was neither prognostic with these cut-offs nor other exploratory cut-offs, nor were predictive for survival benefit from adjuvant chemotherapy.
CONCLUSIONS
PD-L1 IHC is not a prognostic factor in early stage NSCLC patients. It is also not predictive for adjuvant chemotherapy benefit in these patients.
背景
通过免疫组织化学（IHC）评估的程序性死亡（PD）配体1（PD-L1）蛋白表达与晚期非小细胞肺癌（NSCLC）患者对抗PD-1/PD-L1免疫检查点抑制剂治疗的反应及生存获益相关。几种药物的疗效似乎与PD-L1表达相关。PD-L1在NSCLC中是否具有预后价值仍存在争议。我们评估了PD-L1免疫组化的预后价值及其对早期NSCLC辅助化疗的预测作用。
患者和方法
在这项汇总分析中，研究了来自三项关键辅助化疗试验（IALT、JBR.10、CALGB 9633）使用E1L3N抗体的肿瘤切片。由两名病理学家对肿瘤细胞（TCs）和免疫细胞（ICs）中的PD-L1染色强度和百分比进行评分。不同强度和/或染色细胞百分比的平均或一致PD-L1表达水平与临床病理和分子特征、患者生存率以及辅助化疗的潜在获益相关。
结果
982例患者的结果可供分析。对于总体PD-L1表达，无论染色强度如何，分别使用≥1%、≥10%和≥25%的临界值时，314例（32.0%）、204例（20.8%）和141例（14.3%）肿瘤样本的TCs上PD-L1染色呈阳性。对于表达PD-L1的ICs，分别使用≥1%、≥10%和25%的临界值时，380例（38.7%）、308例（31.4%）和148例（15.1%）呈阳性。PD-L1阳性与鳞状组织学、强烈的淋巴细胞浸润和KRAS相关，但与TP53突变无关。表皮生长因子受体（EGFR）突变的肿瘤显示PD-L1表达在统计学上无显著降低。这些临界值以及其他探索性临界值下，PD-L1表达既无预后意义，也不能预测辅助化疗的生存获益。
结论
PD-L1免疫组化不是早期NSCLC患者的预后因素。它也不能预测这些患者辅助化疗的获益情况。
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