Department of Pathology, Sacro Cuore Don Calabria Hospital, Negrar, Verona, Italy; Department of Diagnostics and Public Health, University of Verona, Verona, Italy.
Department of Pathology, Sacro Cuore Don Calabria Hospital, Negrar, Verona, Italy; Department of Diagnostics and Public Health, University of Verona, Verona, Italy.
J Thorac Oncol. 2018 Aug;13(8):1113-1120. doi: 10.1016/j.jtho.2018.04.017. Epub 2018 Apr 25.
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.
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.
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.
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.
程序性死亡配体 1（PD-L1）表达的测定确定了晚期 NSCLC 患者接受 pembrolizumab 治疗的资格。本研究旨在更好地定义同一病例的核心活检标本中哪个值更能反映整个切片的 PD-L1 表达状态，以及需要多少个核心活检标本才能有把握地对肿瘤的 PD-L1 表达进行分类。
我们构建了组织微阵列作为活检的替代品，从 268 例病例中每例收集 5 个核心，并比较了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。
我们发现，在 1%的截断值下，39%的病例呈阳性，在 50%的截断值下，10%的病例呈阳性。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整体假阴性病例的数量最少相关。要达到与整个切片的高度一致性，在 1%和 50%的截断值下，分别需要 4 个和 3 个核心。重要的是，在以 20%作为核心活检标本的截断值时，少于 3 个核心在识别整个切片上有 50%或更多肿瘤细胞阳性的 PD-L1 的病例中表现出高灵敏度和特异性。具体来说，对于核心上的 PD-L1 表达值为 20%至 49%，肿瘤标本在整个切片上至少有 50%的细胞表达 PD-L1 的概率分别为 46%和 24%，使用一个和两个活检标本时。
准确确定确定特定肿瘤 PD-L1 状态的标准可能会极大地帮助选择那些可能从抗程序性细胞死亡 1/PD-L1 治疗中获益的患者。
