Department of Pathology and Laboratory Medicine, the University of Kansas Medical Center, Kansas City, KS 66160.
Department of Radiation Oncology, the University of Kansas Medical Center, Kansas City, KS 66160.
Hum Pathol. 2018 Feb;72:28-34. doi: 10.1016/j.humpath.2017.08.010. Epub 2017 Aug 31.
The interaction of programmed cell death-1 and its ligand-1 (PD-L1) serves as a regulatory check against excessive immune response to antigen and autoimmunity. We compared the performance of 3 different PD-L1 antibodies (Ventana SP263, Dako 22C3, and BioCare RbMCAL10 antibodies) in 136 invasive ductal carcinoma specimens including 43 primary, 48 locally metastatic, and 46 distantly metastatic diseases. PD-L1 expression was correlated with clinicopathologic parameters including tumor size, grade, lymphovascular invasion, estrogen receptor, progesterone receptor, HER2, Ki67, molecular type, and triple-negative status. There was excellent agreement between the 3 antibodies, with highly significant κ values (P≤.001). PD-L1 expression was more likely to be associated with higher tumor grade and estrogen receptor-negative, progesterone receptor-negative, triple-negative, and highly proliferative tumors (P<.001). When we studied PD-L1 expression at 0, 1%-9%, 10%-49%, and ≥50% cutoff points by the 3 antibodies, there were 20 discordant cases between the antibodies. Sixteen were of inconsequential impact as far as low and high PD-L1 expression. The 4 differences between antibodies did exhibit an interesting pattern of expression, where there was a general agreement between the BioCare and Ventana antibodies with consistently higher PD-L1 expression compared with the Dako antibody. Given the high concordance, it is not surprising that all 3 antibodies demonstrated the same associations with all pathologic and clinical parameters studied. Standardization studies to identify reliable biomarkers that help in patient selection for immune therapy to improve the risk-benefit ratio for these drugs are still needed.
程序性细胞死亡受体-1（PD-1）与其配体-1（PD-L1）的相互作用是一种针对抗原过度免疫反应和自身免疫的调节检查点。我们比较了 3 种不同的 PD-L1 抗体（Ventana SP263、Dako 22C3 和 BioCare RbMCAL10 抗体）在 136 例浸润性导管癌标本中的表现，包括 43 例原发性、48 例局部转移性和 46 例远处转移性疾病。PD-L1 的表达与包括肿瘤大小、分级、脉管侵犯、雌激素受体、孕激素受体、HER2、Ki67、分子类型和三阴性状态在内的临床病理参数相关。这 3 种抗体之间具有极好的一致性，κ 值高度显著（P≤.001）。PD-L1 表达更可能与更高的肿瘤分级以及雌激素受体阴性、孕激素受体阴性、三阴性和高增殖性肿瘤相关（P<.001）。当我们使用这 3 种抗体研究 PD-L1 表达在 0、1%-9%、10%-49%和≥50%截点时，有 20 例抗体之间存在不一致。其中 16 例对低表达和高表达 PD-L1 的影响不大。抗体之间的 4 种差异确实表现出一种有趣的表达模式，即 BioCare 和 Ventana 抗体之间具有普遍的一致性，与 Dako 抗体相比，PD-L1 表达更高。考虑到高度一致性，这并不奇怪，所有 3 种抗体都与所有研究的病理和临床参数表现出相同的关联。仍需要标准化研究来确定可靠的生物标志物，以帮助患者选择免疫治疗，从而提高这些药物的风险效益比。
