Intratumoral heterogeneity of programmed cell death ligand-1 expression is common in lung cancer.
Intratumoral heterogeneity of programmed cell death ligand-1 expression is common in lung cancer.
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DOI：
10.1371/journal.pone.0186192
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Fukuoka J
中科院分区：
文献类型：
--
作者：
Nakamura S;Hayashi K;Imaoka Y;Kitamura Y;Akazawa Y;Tabata K;Groen R;Tsuchiya T;Yamasaki N;Nagayasu T;Fukuoka J
程序性细胞死亡配体 1 (PD-L1) 表达可以预测肺癌中程序性细胞死亡 1 和 PD-L1 抑制剂的反应。然而，PD-L1 表达的肿瘤内异质性程度很大程度上尚未被探索，这可能导致假阴性结果。我们的目的是通过应用一种新的组织微阵列方法（即螺旋阵列）来评估手术切除的肺癌标本中 PD-L1 表达的瘤内异质性，该方法使我们能够观察螺旋形组织核心的异质性。腺癌和鳞状细胞癌标本取自自 2009 年以来在长崎大学医院（日本长崎）接受手术切除的连续肺癌患者。小细胞肺癌和大细胞癌标本选自同一档案中自 1998 年以来接受过手术切除的患者。螺旋阵列由螺旋形核心构建，由每个病例的代表性块制备，使用抗 PD-L1 抗体。每个核心分为 8 个片段，每个片段分别使用 1.0%、5.0%、10.0% 和 50.0% 的阈值分为 PD-L1 阳性或 PD-L1 阴性。共选取标本138例，其中腺癌60例，鳞状细胞癌59例，小细胞肺癌12例，大细胞癌7例。大多数具有 PD-L1 阳性片段的样本表现出异质表达（即，核心内混合有 PD-L1 阳性和 PD-L1 阴性片段），无论阈值如何（1.0%，66.7%；5.0%，74.4%；10.0%，75.8%；和 50.0%，85.7%）。在不少于 50.0%（范围为 50.0-76.0%）的具有异质性 PD-L1 表达的病例中，观察到至少 50.0% 的片段呈阴性。因此，在肺癌病例中经常观察到肿瘤内的 PD-L1 表达异质性。因此，可能需要多个肿瘤活检标本才能准确确定 PD-L1 表达状态。
Programmed cell death ligand-1 (PD-L1) expression may predict the response to both programmed cell death-1 and PD-L1 inhibitors in lung cancer. However, the extent of intratumoral heterogeneity of PD-L1 expression, which may cause false negative results, is largely unexplored. We aimed to assess the intratumoral heterogeneity of PD-L1 expression in surgically resected lung cancer specimens by applying a novel method of tissue microarray, namely Spiral Arrays, which enables us to observe the heterogeneity in spiral-shaped tissue cores. Adenocarcinoma and squamous cell carcinoma specimens were obtained from consecutive patients with lung cancer who had undergone surgical resection at Nagasaki University Hospital (Nagasaki, Japan) since 2009. Small cell lung cancer and large cell carcinoma specimens were selected from patients in the same archive who had undergone resection since 1998. Spiral Arrays were constructed of spiral-shaped cores, prepared from representative blocks of each case, which were subjected to immunohistochemistry using an anti-PD-L1 antibody. Each core was divided into 8 segments and each segment was classified as either PD-L1-positive or PD-L1-negative using thresholds of 1.0%, 5.0%, 10.0%, and 50.0%, respectively. In total, 138 specimens were selected, including 60 adenocarcinomas, 59 squamous cell carcinomas, 12 small cell lung cancers, and 7 large cell carcinomas. The majority of specimens with PD-L1-positive segments exhibited heterogeneous expression (i.e., had a mixture of PD-L1-positive and PD-L1-negative segments within a core) irrespective of the threshold (1.0%, 66.7%; 5.0%, 74.4%; 10.0%, 75.8%; and 50.0%, 85.7%]. Large variations in the ratios of PD-L1-positive segments were observed. At least 50.0% of the segments within a core were negative in no fewer than 50.0% (range, 50.0–76.0%) of cases with heterogeneous PD-L1 expression. In conclusion, intratumoral heterogeneity of PD-L1 expression was frequently observed in cases of lung cancer. Thus, multiple tumor biopsy specimens may be needed to accurately determine the PD-L1 expression status.
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作者：
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