Background: Programmed death ligand-1 (PD-L1) assessed by immunohistochemistry (IHC) is used as biomarker for pembrolizumab therapy in advanced stage lung cancer patients. However, data permitting direct performance comparison between cytology and surgical specimen types are limited since both specimens from a single tumor site are infrequently available. In addition, alcohol fixation used with cytology specimens requires technical validation of the PD-L1 IHC assay before clinical use. We here report our experience with implementation of the PD-L1 22C3 IHC pharmDx^TM assay for cytologic samples at a large tertiary cancer center. Study Design: Archival formalin-fixed (FF), paraffin-embedded cell blocks (CBs) and subsequent lung tumor resections (LTRs) from the same anatomical site were used for a direct comparison of PD-L1 tumor proportion scores (TPSs). TPS values were independently determined by one surgical lung pathologist and two cytopathologists blinded to the specimen pairs. An interim analysis was performed to facilitate the pooling of expertise among observers. After PD-L1 22C3 IHC pharmDx^TM implementation for FF cytology specimens, dual-processed samples were used for a prospective technical validation of CytoLyt® prefixation (CF). Digital image analysis was performed for a subset of dual-processed specimens. Results: Eighty-one CBs and LTRs were included for comparison of the specimen types. PD-L1 assessment in CBs had an accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of 88.9/72.8, 66.7/73.5, 95.2/72.3, 80.0/65.8, and 90.9/79.1% for the ≥50/≥1% cutoff, respectively. The intraclass correlation coefficient was 0.84 (95% confidence interval [CI]: 0.76, 0.90), and it improved after interim analysis (before: 0.79 and after: 0.92). The overall concordance between CF and FF for the categories defined by the ≥50/≥1% cutoff values was 90.4% (95% CI: 79.0, 96.8). Similar assay performance was confirmed by digital analysis. Conclusions: PD-L1 22C3 IHC pharmDx^TM shows good reliability if used with CB preparations. CF does not impact assay results significantly. Clinical validation with outcome data is needed, and digital methods of assessment should be further investigated.
Acta Cytologica

中文翻译：

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PD-L1 22C3 IHC pharmDxTM 在肺癌细胞块制备中的实施：与手术切除和 CytoLyt® 预固定技术验证的一致性。

背景：通过免疫组织化学 (IHC) 评估的程序性死亡配体-1 (PD-L1) 被用作晚期肺癌患者派姆单抗治疗的生物标志物。然而，允许在细胞学和手术标本类型之间进行直接性能比较的数据有限，因为来自单个肿瘤部位的两种标本很少可用。此外，细胞学标本的酒精固定需要在临床使用前对 PD-L1 IHC 检测进行技术验证。我们在这里报告我们在大型三级癌症中心对细胞学样本^{实施 PD-L1 22C3 IHC pharmDx TM}检测的经验研究设计：使用存档的福尔马林固定 (FF)、石蜡包埋的细胞块 (CB) 和随后来自同一解剖部位的肺肿瘤切除术 (LTR) 来直接比较 PD-L1 肿瘤比例评分 (TPS)。TPS 值由一名外科肺病理学家和两名对样本对不知情的细胞病理学家独立确定。进行了中期分析，以促进观察员之间汇集专业知识。在对 FF 细胞学样本实施PD-L1 22C3 IHC pharmDx ^TM后，使用双重处理样本对 CytoLyt® 前缀 (CF) 进行前瞻性技术验证。对双重处理样本的子集进行了数字图像分析。结果： 81 个 CB 和 LTR 被纳入样本类型的比较。CB 中 PD-L1 评估的准确性、敏感性、特异性、阳性预测值和阴性预测值对于 ≥50/≥ 的患者分别为 88.9/72.8、66.7/73.5、95.2/72.3、80.0/65.8 和 90.9/79.1%分别为 1% 的截止值。组内相关系数为0.84（95%置信区间[CI]：0.76、0.90），中期分析后有所改善（之前：0.79，之后：0.92）。对于由 ≥50/≥1% 截止值定义的类别，CF 和 FF 之间的总体一致性为 90.4%（95% CI：79.0、96.8）。数字分析证实了类似的测定性能。结论： PD-L1 22C3 IHC pharmDx ^TM如果与 CB 制剂一起使用，显示出良好的可靠性。CF 不会显着影响测定结果。需要使用结果数据进行临床验证，并且应进一步研究数字评估方法。
细胞学学报