Pagni Fabio, Malapelle Umberto, Doglioni Claudio, Fontanini Gabriella, Fraggetta Filippo, Graziano Paolo, Marchetti Antonio, Guerini Rocco Elena, Pisapia Pasquale, Vigliar Elena V, Buttitta Fiamma, Jaconi Marta, Fusco Nicola, Barberis Massimo, Troncone Giancarlo
Department of Medicine and Surgery, Pathology, University Milan Bicocca, 20126 Milan, Italy.
Department of Public Health, University of Naples Federico II, 80131 Naples, Italy.
Cancers (Basel). 2020 Jul 5;12(7):1800. doi: 10.3390/cancers12071800.
A meeting among expert pathologists was held in 2019 in Rome to verify the results of the previous harmonization efforts on the PD-L1 immunohistochemical testing by scoring a representative series of non-small cell lung cancer (NSCLC) digital slides. The current paper shows the results of this digital experimental meeting and the expertise achieved by the community of Italian pathologists. PD-L1 protein expression was determined using tumor proportion score (TPS), i.e., the percentage of viable tumor cells showing partial or complete membrane staining at any intensity. The gold standard was defined as the final PD-L1 score formulated by a panel of seven lung committed pathologists. PD-L1 status was clustered in three categories, namely negative (TPS < 1), low (TPS 1-49%), and high (TPS ≥ 50%). In 23 cases (71.9%) PD-L1 staining was performed using the companion diagnostic 22C3 pharmDx kit on Dako Autostainer, while in nine (28.1%) cases it was performed using the SP263 Ventana kit on BenchMark platform. A complete PD-L1 scoring agreement between the panel of experts and the participants was reached in 57.1% of cases, whereas a minor disagreement in 16.1% of cases was recorded. Italian pathologists performed best in strong positive cases (i.e., tumor proportion score TPS > 50%), whereas only 10.8% of disagreement with the gold standard was observed, and 55.6% regarded a single challenging case. The worst performance was achieved in the negative cases, with 32.0% disagreement. A significant difference resulted from the analysis of the data separated by the different clones used: 22.3% and 38.1% disagreement ( = 0.01) was found in the group of cases analyzed by 22C3 and SP263 antibody clones, respectively. In conclusion, this workshop record proposed the application of a digital pathology platform to share controversial cases in educational meetings as an alternative possibility for improving the interpretation and reporting of specific histological tools. Due to the crucial role of PD-L1 TPS for the selection of patients for immunotherapy, the identification of unconventional approaches as virtual slides to focus experiences and give more detailed practical verifications of the standard quality reached may be a considerable option.
2019年，专家病理学家们在罗马召开了一次会议，通过对一系列具有代表性的非小细胞肺癌（NSCLC）数字切片进行评分，以验证此前在PD-L1免疫组化检测方面的协调工作成果。本文展示了此次数字实验会议的结果以及意大利病理学家群体所取得的专业经验。使用肿瘤比例评分（TPS）来确定PD-L1蛋白表达，即显示任何强度的部分或完全膜染色的存活肿瘤细胞的百分比。金标准定义为由七名专注于肺部疾病的病理学家组成的小组制定的最终PD-L1评分。PD-L1状态分为三类，即阴性（TPS < 1）、低表达（TPS 1-49%）和高表达（TPS≥50%）。在23例（71.9%）病例中，使用配套诊断试剂22C3 pharmDx试剂盒在达科自动染色仪上进行PD-L1染色，而在9例（28.1%）病例中，使用SP263 Ventana试剂盒在BenchMark平台上进行染色。专家小组与参与者之间在57.1%的病例中达成了完全的PD-L1评分一致，而在16.1%的病例中记录到了轻微分歧。意大利病理学家在强阳性病例（即肿瘤比例评分TPS > 50%）中表现最佳，与金标准的分歧仅为10.8%，且55.6%认为是单个具有挑战性的病例。在阴性病例中表现最差，分歧率为32.0%。对使用不同克隆分离的数据进行分析产生了显著差异：在分别使用22C3和SP263抗体克隆分析的病例组中，分歧率分别为22.3%和38.1%（ = 0.01）。总之，本次研讨会记录提出应用数字病理平台在教育会议上分享有争议的病例，作为改进特定组织学工具的解读和报告的另一种可能性。由于PD-L1 TPS在免疫治疗患者选择中的关键作用，将虚拟切片等非常规方法作为聚焦经验并对达到的标准质量进行更详细实际验证的手段可能是一个相当不错的选择。
