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Comparison of PD-L1 expression and MMR status between primary and matched metastatic lesions in patients with cervical cancer

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Abstract

Purpose

Programmed death-ligand 1 (PD-L1) and DNA mismatch repair (MMR) are considered predictive biomarkers for immunotherapy in cervical cancer. However, their expression in primary tumors and metastases does not always match affecting the course of treatment. We investigated the consistency of their expression in primary and matched recurrent/metastatic lesions from patients with cervical cancer.

Methods

Primary and matched recurrent/metastatic specimens from patients with recurrent cervical cancer (n = 194) were stained for PD-L1 and MMR (MLHI, MSH6, MSH2, and PMS2) using immunohistochemistry. The degree of consistency of PD-L1 and MMR expression in these lesions was analyzed.

Results

The inconsistency rate of PD-L1 expression in primary and recurrent/metastatic lesions was 33.0%, and it varied between the recurrence sites. Positive PD-L1 rate in primary lesions was lower (15.4%) than that in recurrent/metastatic lesions (30.4%). The discordance rate of MMR expression between primary and recurrent/metastatic lesions was 4.1%.

Conclusion

We conclude that to use PD-L1 as a predictive biomarker for immunotherapy, analysis of both metastatic and primary lesions may be required. High consistency rate of MMR expression between primary and metastatic lesions suggests that testing primary lesions alone can be sufficient for guiding the course of therapy, thereby solving the difficulty of obtaining recurrent/metastatic specimens in clinic.

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Funding

This research received no external funding.

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Author notes

  1. Huizhen Liu and Lixin Sun contributed equally.

Authors and Affiliations

  1. Department of Gynecologic Oncology, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, 030013, Shanxi, China

    Huizhen Liu, Lixin Sun & Hongwei Zhao

  2. Department of Pathology, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, 030013, Shanxi, China

    Jing Lian, Lixia Wang, Yanfeng Xi, Guohai Zhao, Jiahong Wang, Xiaoyu Lan, Haiyan Du, Wenxia Yan & Peng Bu

  3. Precision Health Program, Michigan State University, East Lansing, MI, 48824, USA

    Ping Wang & Anna Moore

  4. Department of Radiology, College of Human Medicine, Michigan State University, 766 Service Road, Rm. 2022, East Lansing, MI, 48824, USA

    Ping Wang & Anna Moore

Authors
  1. Huizhen Liu
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  2. Lixin Sun
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  3. Jing Lian
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  4. Lixia Wang
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  14. Hongwei Zhao
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Contributions

All authors have contributed to the study conception and design. Conceptualization, HZ; methodology, YX, LW, JL, and HZ; formal analysis, HL and HZ; investigation, HL, PB, GZ, JW, XL, HD, and WY; data curation, LS, HL, and HZ; writing—original draft preparation, LS and HL; writing—review and editing, PW, AM, and HZ; supervision, AM and HZ. All authors reviewed the manuscript. All authors have read and agreed to the published version of the manuscript.

Corresponding authors

Correspondence to Anna Moore or Hongwei Zhao.

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The authors declare no conflict of interest.

Institutional review board statement

The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Ethics Committee of Shanxi Cancer Hospital (protocol number: 202111 approved on 04/09/2021).

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Informed consent was obtained from all subjects involved in the study.

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Liu, H., Sun, L., Lian, J. et al. Comparison of PD-L1 expression and MMR status between primary and matched metastatic lesions in patients with cervical cancer. J Cancer Res Clin Oncol 149, 11397–11410 (2023). https://doi.org/10.1007/s00432-023-05020-6

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