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Heterogeneous expression of PD-L1 in pulmonary squamous cell carcinoma and adenocarcinoma: implications for assessment by small biopsy.

PD-L1在肺鳞状细胞癌和腺癌中表达的异质性:小活检标本评估的意义

Gniadek TJ,Li QK,Tully E,Chatterjee S,Nimmagadda S,Gabrielson E
阅读:1279 Modern PathologyApr 2017; 30 (4): 472 - 629:530-538 

Abstract

Predicting response to checkpoint blockade therapy for lung cancer has largely focused on measuring programmed death-ligand 1 (PD-L1) expression on tumor cells. PD-L1 expression is geographically heterogeneous within many tumors, however, and we questioned whether small tissue samples, such as biopsies, might be sufficiently representative of PD-L1 expression for evaluating this marker in lung cancer tumors. To evaluate the extent of variability of PD-L1 expression in small tissue samples, and how that variability affects accuracy of overall assessment of PD-L1 in lung cancer, we scored immunohistochemical staining for PD-L1 in tissue microarray cores from a series of 79 squamous cell lung cancers and 71 pulmonary adenocarcinomas. Our study found substantial inconsistencies for the percentages of cells staining positive for PD-L1 among different tissue microarray cores in many cases of both adenocarcinoma and squamous cell carcinoma. This variable scoring was seen at both high levels and low levels of PD-L1 expression, and by further evaluation of cases with discordant results on full-face sections to assess geographic distribution of staining, we found that discordant results among different tissue microarray cores reflected geographic variation of PD-L1 expression in those tumors. Moreover, we found that as a result of heterogeneous expression, the sensitivity of a single small tissue sample can be as low as 85% for detecting PD-L1 expression at scoring thresholds commonly used in clinical practice. Based on these studies, we conclude that many cases of lung cancer could be inaccurately or variably scored for PD-L1 expression with a single biopsy sample. Accordingly, lung cancer patients can be inconsistently classified for PD-L1 expression status, particularly when a threshold for the percentage of positive cells is used to determine eligibility for checkpoint blockade therapy.

摘要

预测肺癌对检查点阻断治疗的疗效主要集中在检测肿瘤细胞上程序性死亡配体1(PD-L1)的表达。PD-L1在许多肿瘤中的表达具有异质性,这里我们提出疑问,在小组织样本中,例如活检标本,PD-L1的表达是否可以充分代表肺癌中该标志物的表达水平。为了评估小组织样本中PD-L1表达的变异程度,以及这种变异性如何影响肺癌PD-L1整体评估的准确性,我们应用组织芯片对79例鳞状细胞癌和71例肺腺癌的PD-L1表达进行了免疫组织化学染色并评分。我们的研究发现,在许多腺癌和鳞状细胞癌的组织芯片中PD-L1染色阳性的细胞百分比存在很大的不一致性。 这种变异性在PD-L1高表达和低表达的样本中都存在,对这些不一致病例的切片进一步全面判读以评估染色的分布情况,我们发现不同组织芯片的不一致结果反映了这些肿瘤中PD-L1表达的异质性。此外,我们发现由于异质性表达,使用临床实践中的评分阈值评估单个小组织样本中PD-L1的表达时,灵敏度可以低至85%。基于这些研究,我们得出结论,单个小活检样本的PD-L1表达可能不能准确的反应许多肺癌病例中PD-L1的表达。因此,肺癌患者PD-L1的表达状态可能会被误判,特别是当使用阳性细胞百分比的阈值来评估免疫检查点阻断治疗的可行性时。

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