Yale School of Medicine, New Haven, CT, USA.
Texas A&M University, College Station, TX, USA.
Mod Pathol. 2020 Sep;33(9):1746-1752. doi: 10.1038/s41379-020-0544-x. Epub 2020 Apr 16.
The US Food and Drug Administration (FDA) approved the PD-L1 immunohistochemical assay, SP142, as a companion test to determine eligibility for atezolizumab therapy in patients with advanced triple negative breast cancer (TNBC) but data in lung cancer studies suggest the assay suffers from poor reproducibility. We sought to evaluate reproducibility and concordance in PD-L1 scoring across multiple pathologists. Full TNBC sections were stained with SP142 and SP263 assays and interpreted for percentage (%) immune cell (IC) staining by 19 pathologists from 14 academic institutions. Proportion of PD-L1 positive cases (defined as ≥1% IC) was determined for each assay as well as concordance across observers. We utilized a new method we call Observers Needed to Evaluate Subjective Tests (ONEST) to determine the minimum number of evaluators needed to estimate concordance between large numbers of readers, as occurs in the real-world setting. PD-L1 was interpreted as positive with the SP142 assay in an average 58% of cases compared with 78% with SP263 (p < 0.0001). IC positive continuous scores ranged from 1 to 95% (mean = 20%) and 1 to 90% (mean = 10%) for SP263 and SP142, respectively. With SP142, 26 cases (38%) showed complete two category (<1% vs. ≥1%) concordance; with SP263, 38 cases (50%) showed complete agreement. The intraclass correlation coefficient (ICC) for two category scoring of SP263 and SP142 was 0.513 and 0.560. ONEST plots showed decreasing overall percent agreement (OPA) as observer number increased, reaching a low plateau of 0.46 at ten observers for SP263 and 0.41 at eight observers for SP142. IC scoring with both assays showed poor reproducibility across multiple pathologists with ONEST analysis suggesting more than half of pathologists will disagree about IC scores. This could lead to many patients either receiving atezolizumab when they are unlikely to benefit, or not receiving atezolizumab when they may benefit.
美国食品和药物管理局（FDA）批准了 PD-L1 免疫组织化学检测试剂盒 SP142，作为一种伴随检测方法，用于确定晚期三阴性乳腺癌（TNBC）患者接受阿特珠单抗治疗的资格，但肺癌研究数据表明该检测方法的重复性较差。我们试图评估多位病理学家在 PD-L1 评分方面的重复性和一致性。使用 SP142 和 SP263 检测试剂盒对完整的 TNBC 切片进行染色，由来自 14 家学术机构的 19 位病理学家对免疫细胞（IC）染色的百分比（%）进行解读。确定了每种检测方法的 PD-L1 阳性病例（定义为≥1%IC）的比例以及观察者之间的一致性。我们利用了一种新的方法，称为评估主观测试所需的观察者数量（ONEST），以确定在实际环境中，大量观察者之间估计一致性所需的最小评估者数量，这种情况经常发生。与 SP263 相比，SP142 检测试剂盒将 PD-L1 判读为阳性的平均比例为 58%，而判读为阳性的比例为 78%（p<0.0001）。SP263 和 SP142 的 IC 阳性连续评分范围分别为 1 至 95%（平均为 20%）和 1 至 90%（平均为 10%）。在 SP142 中，有 26 例（38%）表现出完全的两类别（<1%与≥1%）一致性；在 SP263 中，有 38 例（50%）表现出完全一致。SP263 和 SP142 两类别评分的组内相关系数（ICC）分别为 0.513 和 0.560。ONEST 图显示，随着观察者数量的增加，整体百分比一致性（OPA）逐渐降低，SP263 达到 10 位观察者时的低平台值为 0.46，SP142 达到 8 位观察者时的低平台值为 0.41。两种检测方法的 IC 评分在多位病理学家之间均显示出较差的重复性，ONEST 分析表明，超过一半的病理学家对 IC 评分存在分歧。这可能导致许多患者要么在不太可能受益的情况下接受阿特珠单抗治疗，要么在可能受益的情况下未接受阿特珠单抗治疗。
