Division of Oncology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden.
Department of Oncology and Radiation Physics, Skåne University Hospital, Lund, Sweden.
Breast Cancer Res. 2023 Oct 10;25(1):123. doi: 10.1186/s13058-023-01724-2.
Immunohistochemical (IHC) PD-L1 expression is commonly employed as predictive biomarker for checkpoint inhibitors in triple-negative breast cancer (TNBC). However, IHC evaluation methods are non-uniform and further studies are needed to optimize clinical utility.
We compared the concordance, prognostic value and gene expression between PD-L1 IHC expression by SP142 immune cell (IC) score and 22C3 combined positive score (CPS; companion IHC diagnostic assays for atezolizumab and pembrolizumab, respectively) in a population-based cohort of 232 early-stage TNBC patients.
The expression rates of PD-L1 for SP142 IC ≥ 1%, 22C3 CPS ≥ 10, 22C3 CPS ≥ 1 and 22C3 IC ≥ 1% were 50.9%, 27.2%, 53.9% and 41.8%, respectively. The analytical concordance (kappa values) between SP142 IC+ and these three different 22C3 scorings were 73.7% (0.48, weak agreement), 81.5% (0.63) and 86.6% (0.73), respectively. The SP142 assay was better at identifying 22C3 positive tumors than the 22C3 assay was at detecting SP142 positive tumors. PD-L1 (CD274) gene expression (mRNA) showed a strong positive association with all two-categorical IHC scorings of the PD-L1 expression, irrespective of antibody and cut-off (Spearman Rho ranged from 0.59 to 0.62; all p-values < 0.001). PD-L1 IHC positivity and abundance of tumor infiltrating lymphocytes were of positive prognostic value in univariable regression analyses in patients treated with (neo)adjuvant chemotherapy, where it was strongest for 22C3 CPS ≥ 10 and distant relapse-free interval (HR = 0.18, p = 0.019). However, PD-L1 status was not independently prognostic when adjusting for abundance of tumor infiltrating lymphocytes in multivariable analyses.
Our findings support that the SP142 and 22C3 IHC assays, with their respective clinically applied scoring algorithms, are not analytically equivalent where they identify partially non-overlapping subpopulations of TNBC patients and cannot be substituted with one another regarding PD-L1 detection. Trial registration The Swedish Cancerome Analysis Network - Breast (SCAN-B) study, retrospectively registered 2nd Dec 2014 at ClinicalTrials.gov; ID NCT02306096.
免疫组织化学（IHC）程序性死亡配体 1（PD-L1）表达通常被用作三阴性乳腺癌（TNBC）中检查点抑制剂的预测生物标志物。然而，IHC 评估方法并不统一，需要进一步研究以优化其临床实用性。
我们比较了基于人群的 232 例早期 TNBC 患者中 SP142 免疫细胞（IC）评分和 22C3 联合阳性评分（CPS；分别为阿替利珠单抗和帕博利珠单抗的配套 IHC 诊断检测）的 PD-L1 IHC 表达之间的一致性、预后价值和基因表达。
SP142 IC≥1%、22C3 CPS≥10、22C3 CPS≥1 和 22C3 IC≥1%的 PD-L1 表达率分别为 50.9%、27.2%、53.9%和 41.8%。SP142 IC+与这三种不同的 22C3 评分之间的分析一致性（kappa 值）分别为 73.7%（0.48，弱一致性）、81.5%（0.63）和 86.6%（0.73）。SP142 检测法比 22C3 检测法更能识别 22C3 阳性肿瘤。PD-L1（CD274）基因表达（mRNA）与 PD-L1 表达的所有两种分类 IHC 评分均呈强正相关，与抗体和截止值无关（Spearman Rho 范围为 0.59 至 0.62；所有 p 值均<0.001）。在接受（新）辅助化疗的患者中，PD-L1 IHC 阳性和肿瘤浸润淋巴细胞的丰度在单变量回归分析中具有阳性预后价值，其中 22C3 CPS≥10 和远处无复发生存间隔的作用最强（HR=0.18，p=0.019）。然而，在多变量分析中调整肿瘤浸润淋巴细胞丰度后，PD-L1 状态并非独立的预后因素。
我们的研究结果支持 SP142 和 22C3 IHC 检测法，它们具有各自的临床应用评分算法，在识别 TNBC 患者的部分非重叠亚群方面并不具有分析等效性，并且不能相互替代以检测 PD-L1。
瑞典癌症分析网络-乳房（SCAN-B）研究，于 2014 年 12 月 2 日在 ClinicalTrials.gov 进行回顾性注册；ID NCT02306096。
