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. 2025 Aug;212(3):569-576.
doi: 10.1007/s10549-025-07757-9. Epub 2025 Jun 11.

PD-L1 22C3 CPS in paired primary breast cancer and lung metastasis

Eunah Shin  1 , Yoon Jin Cha  1 , Hye Min Kim  1 , Ja Seung Koo  2
Affiliations

PD-L1 22C3 CPS in paired primary breast cancer and lung metastasis

Eunah Shin et al. Breast Cancer Res Treat. 2025 Aug.

Abstract

Purpose: This study aimed to evaluate the expression of PD-L1 22C3 in primary breast cancer and lung metastasis tissues using the Combined Positive Score (CPS) and to investigate the concordance and differences between them.

Methods: Immunohistochemical staining for PD-L1 22C3 was performed on 52 paired cases of primary breast cancer and lung metastases. The CPS was measured and analyzed for comparison.

Results: The PD-L1 positivity rate (CPS ≥ 10) was 13.5% in primary breast cancers and 30.8% in lung metastases. The overall percent agreement (OPA) for PD-L1 CPS between primary tumors and lung metastases was 78.8%, with a positive percent agreement (PPA) of 85.7% and a negative percent agreement (NPA) of 77.8%. The mean CPS was 2.69 ± 6.67 (mean ± SD) in primary breast cancers and 7.67 ± 14.49 (mean ± SD) in lung metastases, with a significantly higher CPS observed in lung metastases (p < 0.001). The primary cause of discordance, where PD-L1 was negative in the primary tumor but positive in the metastasis, was the presence of PD-L1-positive alveolar macrophages predominantly located around or within the metastatic tumor.

Conclusion: PD-L1 22C3 demonstrated approximately 80% concordance between primary breast cancers and lung metastases; however, discordance was mainly attributable to the presence of inherently PD-L1-positive peritumoral and/or intratumoral alveolar macrophages.

Keywords: Breast cancer; Lung metastasis; PD-L1.

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Conflict of interest statement

Declarations. Conflict of interest: The authors have no conflicts of interest to declare. Ethical approval: The study adhered to the principles of the Declaration of Helsinki and obtained approval from the Institutional Review Board of Yonsei University Severance Hospital (IRB number: IRB number: 4-2024-0276). Consent to participate: Due to the retrospective nature of the study, patient consent was exempted by the Institutional Review Board of Yonsei University Severance Hospital.

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