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Discordance in PD-L1 expression using 22C3 and SP142 assays between primary and metastatic triple-negative breast cancer

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Abstract

Aims

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.

Methods

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).

Results

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.

Conclusions

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.

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Data availability statement

The datasets analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We thank Shoichi Harada, Sachiko Miura, Toshiko Sakaguchi, and Chizu Kina for technical assistance. We thank Editage (http://www.editage.com) for English language editing.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Department of Medical Oncology, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan

    Jun Miyakoshi, Shu Yazaki, Tatsunori Shimoi, Mai Onishi, Ayumi Saito, Shosuke Kita, Kasumi Yamamoto, Yuki Kojima, Hitomi Sumiyoshi-Okuma, Tadaaki Nishikawa, Kazuki Sudo, Emi Noguchi, Yasuhiro Fujiwara & Kan Yonemori

  2. Department of Thoracic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan

    Jun Miyakoshi

  3. Department of Breast Surgery, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan

    Takeshi Murata, Sho Shiino, Shin Takayama & Akihiko Suto

  4. Department of Diagnostic Pathology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan

    Masayuki Yoshida

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  1. Jun Miyakoshi
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Contributions

JM, SY, and MY made substantial contributions to the study concept, the data analysis or interpretation, and drafting of the original manuscript; SY, TS, MO, AS, SK, KY, YK, HS(O), TN, KS, EN, TM, SS, ST, AS, YF, and KY made substantial contributions to the acquisition of data in this study; All authors reviewed the manuscript draft, revised it critically on intellectual content, and approved the final version of the manuscript to be published.

Corresponding author

Correspondence to Masayuki Yoshida.

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Ethics approval statement

This study was approved by the Institutional Review Board of the National Cancer Center (No. 2014–092).

Competing isnterests

Masayuki Yoshida reports personal fees from Roche Japan, Eli Lilly, Chugai, MSD, Daiichi Sankyo, Ono, Agilent technologies outside of the submitted work. Tadaaki Nishikawa reports personal fees from Takeda Pharmaceutical Company, Eisai, and AstraZeneca outside of the submitted work. Emi Noguchi reports personal fees from Pfizer, Taiho, Eli Lilly, AstraZeneca, Chugai, and Eisai outside the submitted work. Kan Yonemori reports receiving grants from Merck Sharp & Dohme, Daiichi-Sankyo, AstraZeneca, Taiho, Pfizer, Novartis, Takeda, Chugai, Ono, Seattle Genetics, Eisai, Eli Lilly, Genmab, Boehringer Ingelheim, Kyowa Hakko Kirin, Nihon Kayaku, and Haihe; personal fees from Pfizer, Eisai, Astrazeneca, Eli Lilly, Takeda, Chugai, MSD, FujiFilm Pharma, Bayer, Asteras, Boeringer Ingelheim, Daiichi Sankyo, PDR pharma, Sanofi outside the submitted work.

Patient consent statement

The need for informed consent was waived because of the retrospective nature of the study.

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Miyakoshi, J., Yazaki, S., Shimoi, T. et al. Discordance in PD-L1 expression using 22C3 and SP142 assays between primary and metastatic triple-negative breast cancer. Virchows Arch 483, 855–863 (2023). https://doi.org/10.1007/s00428-023-03634-2

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