A Comprehensive Analysis of Programmed Cell Death Ligand-1 Expression With the Clone SP142 Antibody in Non-Small-Cell Lung Cancer Patients
A Comprehensive Analysis of Programmed Cell Death Ligand-1 Expression With the Clone SP142 Antibody in Non-Small-Cell Lung Cancer Patients
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DOI：
10.1016/j.cllc.2017.02.004
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发表时间：
2017-09-01
影响因子：
3.6
通讯作者：
Maehara, Yoshihiko
中科院分区：
文献类型：
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作者：
Takada, Kazuki;Toyokawa, Gouji;Maehara, Yoshihiko
我们使用克隆SP142和4种不同的截断值，检测了499例手术切除的非小细胞肺癌(NSCLC)患者的程序性细胞死亡配体-1(PD-L1)的表达。PD-L1在NSCLC中的表达根据不同的临界值有很大差异，并与NSCLC患者的生存不良有关。背景：程序性细胞死亡-1(PD-1)和程序性细胞死亡配体-1(PD-L1)已被确定为免疫治疗的新靶点，在一线化疗失败后，抗ePD-1治疗目前是非小细胞肺癌(NSCLC)患者的标准治疗。最近的第二期杨树和第三期橡树研究表明，与标准疗法相比，具有代表性的PD-L1抑制剂阿替唑单抗在非小细胞肺癌患者中显示出生存优势。患者和方法：我们使用杨树和橡树的克隆SP142检测了PD-L1在非小细胞肺癌中的表达。应用免疫组织化学SP142法检测499例手术切除的非小细胞肺癌组织中PD-L1的表达。我们将截止值设置为1%、5%、10%和50%。结果：以1%、5%、10%和50%为界值，189例(37.9%)、119例(23.8%)、71例(14.2%)和39例(7.8%)标本中PD-L1表达阳性。Fisher精确检验显示，PD-L1阳性与男性、吸烟、晚期、血管侵犯、鳞状细胞癌和野生型表皮生长因子受体基因突变状态在所有临界值均显著相关。单因素和多因素生存分析显示，PD-L1阳性患者的预后比PD-L1阴性患者差，仅在1%的临界值。森林图分析显示，1%的临界值对预测术后预后有较高的敏感性。结论：PD-L1的表达在不同的临界值之间有较大差异。这项研究可能对了解杨树和橡树研究的结果以及选择可能受益于阿替唑单抗的患者提供有用的参考。(C)2017 Elsevier Inc.保留所有权利。
We examined programmed cell death ligand-1 (PD-L1) expression in 499 surgically resected non-small-cell lung cancer (NSCLC) patients using the clone SP142 and 4 different cutoff values. PD-L1 expression in NSCLC was shown to vary greatly according to different cutoff values, and to be associated with poor survival in NSCLC patients. This study might be a useful reference to understand the results of the POPLAR and OAK studies.Background: Programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) have been identified as novel targets for immunotherapy, with antiePD-1 therapy currently the standard treatment for non-small-cell lung cancer (NSCLC) patients after the failure of first-line chemotherapy treatment. The recent phase II POPLAR and phase III OAK studies showed that atezolizumab, a representative PD-L1 inhibitor, exhibited a survival benefit compared with standard therapy in patients with NSCLC. Patients and Methods: We examined PD-L1 expression in NSCLC using the clone SP142 of POPLAR and OAK studies. PD-L1 expression in 499 surgically resected NSCLC patients was evaluated using immunohistochemistry using SP142. We set cutoff values as 1%, 5%, 10%, and 50%. Results: The samples from 189 (37.9%), 119 (23.8%), 71 (14.2%), and 39 (7.8%) patients were positive for PD-L1 expression at cutoff values of 1%, 5%, 10%, and 50%, respectively. Fisher exact tests showed that PD-L1 positivity was significantly associated with male sex, smoking, advanced stage, the presence of vascular invasion, squamous cell carcinoma, and wild type epidermal growth factor receptor gene mutation status at all cutoff values. Univariate and multivariate survival analyses revealed that PD-L1-positive patients had a worse prognosis than PD-L1-negative patients only at the 1% cutoff value. Forest plot analyses showed that the 1% cutoff provided a more sensitive value for the prediction of postoperative prognosis. Conclusion: PD-L1 expression varied greatly according to different cutoff values. This study might be a useful reference to understand the results of POPLAR and OAK studies and to select patients likely to benefit from atezolizumab. (C) 2017 Elsevier Inc. All rights reserved.