Pathology Department of the Russian Medical Academy of Continuous Professional Education, Moscow, Russia.
Russian Society of Pathology, Moscow, Russia.
Virchows Arch. 2018 Dec;473(6):719-724. doi: 10.1007/s00428-018-2453-7. Epub 2018 Sep 13.
In this collaborative study by the Russian Society of Clinical Oncology and the Russian Society of Pathology, we assessed the concordance among three validated, commercially available PD-L1 immunohistochemistry assays for patients with urothelial cancer. Tumors from 100 urothelial cancer patients were stained with the antibody clones 22C3 (Agilent), SP142 (Ventana Medical Systems), and SP263 (Ventana Medical Systems), which are used in clinical trials of second-line therapy with checkpoint inhibitors. Four trained pathologists independently evaluated the percentages of tumor cells (TC) and tumor-infiltrating immune cells (IC) that were stained at any intensity by each of the antibodies. The test-specific cutoffs for the proportions of stained cells in a positive sample were pre-specified as TC + IC ≥ 10% or TC ≥ 10% for 22C3, IC ≥ 5% for SP142, and TC ≥ 25% or IC ≥ 25% for SP263. Three hundred immunohistochemistry slides were scored. The percentages of PD-L1 staining in the three assays without using any cutoff were higher in the IC than in the TC (55% versus 24% for 22C3, 45% versus 8% for SP142, and 72% versus 27% for SP263, respectively). The Pearson correlation coefficients for anti-PD-L1 staining in the IC were 0.5, 0.69, and 0.85 with 22C3/SP142, 22C3/SP263, and SP142/SP263, respectively. The Pearson correlation coefficients for PD-L1 staining in the TC were 0.93, 0.99, and 0.91 for the same pairs. Among the patients who were negative for PD-L1 staining by one test, 91-100% were also negative by the other tests. Among the patients who were positive by one test, 43-100% were also positive by the other tests. Our data indicate that repeated testing can be avoided as a patient with urothelial cancer who is classified as negative for PD-L1 expression by one of the three single tests using the corresponding cutoff rule is highly likely (91-100%) to be classified as negative by either of the other tests.
在这项由俄罗斯临床肿瘤学会和俄罗斯病理学会合作进行的研究中，我们评估了三种经过验证的、商业可用的 PD-L1 免疫组织化学检测方法在尿路上皮癌患者中的一致性。100 例尿路上皮癌患者的肿瘤用抗体克隆 22C3（Agilent）、SP142（Ventana Medical Systems）和 SP263（Ventana Medical Systems）染色，这些抗体用于二线治疗检查点抑制剂的临床试验。四位经过培训的病理学家独立评估了每种抗体染色的肿瘤细胞（TC）和肿瘤浸润免疫细胞（IC）的百分比。阳性样本中染色细胞比例的特定测试截止值预先指定为 TC + IC ≥ 10%或 22C3 的 TC ≥ 10%，SP142 的 IC ≥ 5%，SP263 的 TC ≥ 25%或 IC ≥ 25%。对 300 张免疫组化切片进行了评分。在不使用任何截止值的情况下，三种检测方法中 PD-L1 染色的百分比在 IC 中高于 TC（22C3 为 55%比 24%，SP142 为 45%比 8%，SP263 为 72%比 27%）。IC 中抗 PD-L1 染色的 Pearson 相关系数分别为 0.5、0.69 和 0.85，与 22C3/SP142、22C3/SP263 和 SP142/SP263 相对应。TC 中 PD-L1 染色的 Pearson 相关系数分别为 0.93、0.99 和 0.91，与上述三组相对应。在一种检测方法中 PD-L1 染色阴性的患者中，91-100%也在另一种检测方法中为阴性。在一种检测方法中阳性的患者中，43-100%也在另一种检测方法中为阳性。我们的数据表明，可以避免重复检测，因为使用相应的截止值规则，用三种单检测方法中的一种方法分类为 PD-L1 表达阴性的尿路上皮癌患者很可能（91-100%）被另一种方法分类为阴性。
