Comparison of SP142 and 22C3 PD-L1 assays in a population-based cohort of triple-negative breast cancer patients in the context of their clinically established scoring algorithms

Breast Cancer Research

Research

Johan Hartman¹  Tommaso De Marchi²  Anna Ehinger³  Ana Bosch⁴  Gudbjörg Sigurjonsdottir⁴  Fredrika Killander⁴  Johan Staaf⁵  Emma Niméus⁶ 

[1] Department of Oncology and Pathology, Karolinska Institute and University Hospital, Stockholm, Sweden;Division of Oncology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden;Division of Oncology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden;Department of Clinical Genetics, Pathology and Molecular Diagnostics, Laboratory Medicine, Region Skåne, Lund, Sweden;Division of Oncology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden;Department of Oncology and Radiation Physics, Skåne University Hospital, Lund, Sweden;Division of Oncology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden;Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University, Medicon Village, Lund, Sweden;Division of Oncology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden;Divison of Surgery, Department of Clinical Sciences Lund, Lund University, Sölvegatan 19 - BMC I12, 22184, Lund, Sweden;Department of Surgery, Skåne University Hospital, Malmö, Sweden;

关键词: Triple-negative breast cancer;    PD-L1;    Immunohistochemistry;    SP142;    22C3;    Concordance;    TILs;    Patient outcome;    Gene expression;   

DOI  :  10.1186/s13058-023-01724-2

 received in 2023-04-20, accepted in 2023-10-02,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundImmunohistochemical (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.MethodsWe 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.ResultsThe 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.ConclusionOur 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.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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