Department of Medical Oncology, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan.
Department of Thoracic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan.
Virchows Arch. 2023 Dec;483(6):855-863. doi: 10.1007/s00428-023-03634-2. Epub 2023 Sep 5.
SP142 and 22C3 assays are approved companion diagnostic assays for anti-PD-1/PD-L1 therapy selection in metastatic triple-negative breast cancer (TNBC). The discordance in PD-L1 status between primary and metastatic tumors in the same patient has been poorly characterized. Here, we examined the concordance of PD-L1 status between the two assays and between primary tumors and metastases for each assay.
We retrospectively evaluated tumor samples from 160 patients with TNBC, including 45 patients with paired primary and metastatic tumors. PD-L1 status was assessed using SP142 and 22C3 assays, to determine the immune cell (IC) score, tumor cell (TC) score (SP142 and 22C3), and combined proportion score (CPS: 22C3).
The concordance of PD-L1 positivity at diagnostic cutoffs for SP142 (IC ≥ 1) and 22C3 (CPS ≥ 10) was substantial (κ = 0.80) in primary tumors and moderate (κ = 0.60) in metastatic tumors. In comparison, between primary and metastatic tumors, the concordance with 22C3 was moderate (κ = 0.50), whereas that with SP142 was poor (κ = -0.03). Among patients who were PD-L1 negative for both assays in primary tumors, 7/30 (23.3%) were PD-L1 positive for both or either 22C3 or SP142 in the metastatic tumors.
The inter-assay concordance of PD-L1 positivity at diagnostic cutoffs was substantial in primary tumors and moderate in metastatic tumors. Discordance between PD-L1 status in primary and metastatic tumors was frequently observed, especially with SP142. Some patients with a PD-L1-negative status in primary tumors may still be candidates for immunotherapy, depending on the PD-L1 status in their metastatic tumors.
SP142 和 22C3 检测是转移性三阴性乳腺癌（TNBC）抗 PD-1/PD-L1 治疗选择的获批伴随诊断检测。同一患者的原发肿瘤和转移肿瘤之间的 PD-L1 状态存在差异，但目前对此了解甚少。本研究旨在检测两种检测方法之间以及每种检测方法的原发肿瘤和转移肿瘤之间 PD-L1 状态的一致性。
我们回顾性评估了 160 例 TNBC 患者的肿瘤样本，其中 45 例患者有配对的原发和转移肿瘤。使用 SP142 和 22C3 检测评估 PD-L1 状态，以确定免疫细胞（IC）评分、肿瘤细胞（TC）评分（SP142 和 22C3）和联合比例评分（CPS：22C3）。
在原发肿瘤中，SP142（IC≥1）和 22C3（CPS≥10）的诊断截断值处 PD-L1 阳性的一致性很高（κ=0.80），在转移肿瘤中为中度（κ=0.60）。相比之下，在原发肿瘤和转移肿瘤之间，22C3 的一致性为中度（κ=0.50），而 SP142 的一致性较差（κ=-0.03）。在原发肿瘤两种检测均为 PD-L1 阴性的患者中，有 7/30（23.3%）的转移肿瘤两种或任一种 22C3 或 SP142 检测为 PD-L1 阳性。
在原发肿瘤中，两种检测方法在诊断截断值处 PD-L1 阳性的一致性很高，在转移肿瘤中为中度。原发肿瘤和转移肿瘤之间的 PD-L1 状态差异很常见，尤其是使用 SP142 检测时。一些原发肿瘤 PD-L1 阴性的患者可能仍然是免疫治疗的候选者，这取决于其转移肿瘤的 PD-L1 状态。
