Lou Si Kei, Ko Hyang Mi, Kinoshita Tomonari, MacDonald Scott, Weiss Jessica, Czarnecka-Kujawa Katarzyna, Boerner Scott L, Yasufuku Kazuhiro, Tsao Ming-Sound, Schwock Joerg
Division of Pathology, University Health Network, Toronto, Ontario, Canada.
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
Acta Cytol. 2020;64(6):577-587. doi: 10.1159/000508628. Epub 2020 Jun 29.
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 pharmDxTM assay for cytologic samples at a large tertiary cancer center.
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 pharmDxTM 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.
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.
PD-L1 22C3 IHC pharmDxTM 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.
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帕博利珠单抗治疗的生物标志物。然而，由于很少能获得来自单一肿瘤部位的两种标本，因此允许对细胞学和手术标本类型进行直接性能比较的数据有限。此外，细胞学标本使用的酒精固定需要在临床应用前对PD-L1 IHC检测进行技术验证。我们在此报告我们在一家大型三级癌症中心对细胞学样本实施PD-L1 22C3 IHC pharmDxTM检测的经验。
来自同一解剖部位的存档福尔马林固定（FF）、石蜡包埋细胞块（CB）和随后的肺肿瘤切除术（LTR）用于直接比较PD-L1肿瘤比例评分（TPS）。TPS值由一位手术肺病理学家和两位对标本对不知情的细胞病理学家独立确定。进行了一项中期分析，以促进观察者之间的专业知识汇集。在对FF细胞学标本实施PD-L1 22C3 IHC pharmDxTM后，对双处理样本进行了CytoLyt®预固定（CF）的前瞻性技术验证。对一部分双处理标本进行了数字图像分析。
纳入81个CB和LTR用于标本类型比较。对于≥50/≥1%的截断值，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分别为88.9/72.8、66.7/73.5、95.2/72.3、80.0/65.8和90.9/79.1%。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%截断值定义的类别，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检测性能。
如果与CB制剂一起使用，PD-L1 22C3 IHC pharmDxTM显示出良好的可靠性。CF对检测结果没有显著影响。需要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。
