Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
Cancer Progression Research Center, National Yang-Ming University, Taipei, Taiwan.
Cancer Cytopathol. 2021 Feb;129(2):148-155. doi: 10.1002/cncy.22359. Epub 2020 Sep 25.
Immune checkpoint inhibitor therapy has revolutionized lung adenocarcinoma therapy. Treatment with antibodies against the immune checkpoint molecules programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) can induce a durable response in a subset of patients. Immunohistochemistry characterization of tumor PD-L1 expression using either a histopathology specimen or a cytopathology specimen has been shown to correlate with treatment response. However, the current practice relies on pathologists' visual estimation of tumor PD-L1 staining, which can be variable in certain conditions. Highlighting tumor cells via double immunostaining with PD-L1 and thyroid transcription factor-1 (TTF-1) may improve estimation accuracy.
We performed PD-L1 single staining and PD-L1/TTF-1 double staining in 42 pairs of cytopathology and histopathology specimens from lung adenocarcinoma patients. An experienced pathologist visually estimated PD-L1 expression in each case and placed tumor PD-L1 expression into 1 of 3 categories: <1%, 1%-49%, or ≥50%. A medical technologist also performed estimations of the same cases based on a count of 200 tumor cells, and the results were compared.
PD-L1/TTF-1 double immunohistochemistry could better identify the PD-L1-positive tumor cells in cytopathology specimens compared with PD-L1 single staining. The concordance of PD-L1 expression categorization between the pathologist's visual estimation and the medical technologist's counting was increased by double staining in cytopathology specimens (Cohen's weighted kappa: single stain, 0.784; double stain, 0.880). Double staining reduced possible error in the pathologist's visual estimation of PD-L1 expression from 9.5% to 4.8%. The benefit was not observed in histopathology specimens.
A simple PD-L1/TTF-1 double immunohistochemistry technique can be applied successfully to cytopathology specimens in better identifying patients who can potentially benefit from immune checkpoint blockade treatment.
免疫检查点抑制剂治疗彻底改变了肺腺癌的治疗方法。针对免疫检查点分子程序性死亡受体 1（PD-1）和程序性死亡配体 1（PD-L1）的抗体治疗可以在一部分患者中诱导持久的反应。使用组织病理学标本或细胞学标本对肿瘤 PD-L1 表达进行免疫组织化学特征分析已被证明与治疗反应相关。然而，目前的实践依赖于病理学家对肿瘤 PD-L1 染色的视觉估计，在某些情况下可能存在差异。通过 PD-L1 和甲状腺转录因子-1（TTF-1）的双重免疫染色突出肿瘤细胞可能会提高估计的准确性。
我们对 42 对来自肺腺癌患者的细胞学和组织学标本进行了 PD-L1 单染色和 PD-L1/TTF-1 双重染色。一位经验丰富的病理学家对每种情况进行了 PD-L1 表达的视觉评估，并将肿瘤 PD-L1 表达分为 3 个类别之一：<1%、1%-49%或≥50%。一位医学技师还对相同的病例进行了基于 200 个肿瘤细胞计数的评估，并进行了比较。
与 PD-L1 单染色相比，PD-L1/TTF-1 双重免疫组化可以更好地识别细胞学标本中的 PD-L1 阳性肿瘤细胞。双重染色增加了病理学家视觉评估与医学技师计数之间的 PD-L1 表达分类一致性（细胞学标本的 Cohen 加权 kappa：单染色，0.784；双染色，0.880）。双重染色将病理学家对 PD-L1 表达的视觉估计中的可能错误从 9.5%降低到 4.8%。在组织学标本中未观察到这种获益。
一种简单的 PD-L1/TTF-1 双重免疫组化技术可以成功应用于细胞学标本，更好地识别可能受益于免疫检查点阻断治疗的患者。
