Introduction: Determination of programmed death ligand 1 (PD‐L1) expression defines eligibility for treatment with pembrolizumab in patients with advanced NSCLC. This study was designed to better define which value across core biopsy specimens from the same case more closely reflects the PD‐L1 expression status on whole sections and how many core biopsy specimens are needed for confident classification of tumors in terms of PD‐L1 expression. Methods: We built tissue microarrays as surrogates of biopsies collecting five cores per case from 268 cases and compared PD‐L1 staining results obtained by using the validated clone SP263 with the results obtained by using whole tumor sections. Results: We found an overall positivity in 39% of cases at a cutoff of 1% and in 10% of cases at a cutoff of 50%. The maximum value across cores was associated with high concordance between cores and whole sections and the lowest number of false‐negative cases overall. To reach high concordance with whole sections, four and three cores are necessary at cutoffs of 1% and 50%, respectively. Importantly, with 20% as the cutoff for core biopsy specimens, fewer than three cores showed high sensitivity and specificity in identifying cases with 50% or more of tumor cells positive for PD‐L1 on whole sections. Specifically, for PD‐L1 expression values of 20% to 49% on cores, the probabilities of a tumor specimen expressing PD‐L1 in at least 50% of cells on a whole section were 46% and 24% with one and two biopsy specimens, respectively. Conclusions: An accurate definition of the criteria to determine the PD‐L1 status of a given tumor may greatly help in selecting those patients who could benefit from anti–programmed cell death 1/PD‐L1 treatment.

中文翻译：

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非小细胞肺癌中的 PD-L1 表达异质性：定义活检和整个切片之间的协调标准

简介：程序性死亡配体 1 (PD-L1) 表达的测定决定了晚期 NSCLC 患者接受派姆单抗治疗的资格。本研究旨在更好地定义来自同一病例的核心活检标本的哪个值更能反映整个切片的 PD-L1 表达状态，以及根据 PD-L1 表达对肿瘤进行可靠分类需要多少核心活检标本。方法：我们构建了组织微阵列作为活检的替代物，从 268 个病例中收集每个病例的 5 个核心，并将使用经过验证的克隆 SP263 获得的 PD-L1 染色结果与使用整个肿瘤切片获得的结果进行比较。结果：我们发现 39% 的病例在 1% 的临界值和 10% 的病例中是在 50% 的临界值时总体呈阳性。核心之间的最大值与核心和整个切片之间的高度一致性以及总体假阴性案例的最低数量相关。为了与整个切片保持高度一致，分别需要四个和三个核心，截断值分别为 1% 和 50%。重要的是，以 20% 作为核心活检标本的临界值，少于三个核心在识别整个切片上 50% 或更多肿瘤细胞对 PD-L1 呈阳性的病例时显示出高灵敏度和特异性。具体而言，对于核心上 20% 至 49% 的 PD-L1 表达值，一个和两个活检标本在整个切片上至少 50% 的细胞中表达 PD-L1 的肿瘤标本的概率分别为 46% 和 24% ， 分别。结论：