Basic Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Exp Med. Jun 20, 2025; 15(2): 102761
Published online Jun 20, 2025. doi: 10.5493/wjem.v15.i2.102761
Cytoplasmic and nuclear programmed death ligand 1 expression in peritumoral stromal cells in breast cancer: Prognostic and predictive value
Evgeniya Yu Zubareva, Marina A Senchukova, Natalia V Saidler
Evgeniya Yu Zubareva, Marina A Senchukova, Department of Oncology, Orenburg State Medical University, Orenburg 460021, Orenburgskaya Oblast, Russia
Natalia V Saidler, Department of Pathology, Orenburg Regional Cancer Clinic, Orenburg 460021, Orenburgskaya Oblast, Russia
Author contributions: Zubareva EY designed and performed the research, and wrote the paper; Senchukova MA acquired and analyzed the data and contributed substantially to the conception and design of the study; Saidler NV participated in the discussion of related data, and revised and approved the final version; All authors wrote and approved the final manuscript.
Supported by Russian Science Foundation, No. 23-25-00183.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of Orenburg State Medical University (Russia, Orenburg; protocol No. 311 dated January 13, 2023).
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Data sharing statement: Data from patients included in the study in Statistica10 table or Excel table formats can be provided upon request to the corresponding author at masenchukova@yandex.com.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Marina A Senchukova, MD, PhD, Professor, Department of Oncology, Orenburg State Medical University, 6 Sovetskaya Street, Orenburg 460000, Orenburgskaya Oblast, Russia. masenchukova@yandex.com
Received: October 28, 2024
Revised: January 21, 2025
Accepted: February 21, 2025
Published online: June 20, 2025
Processing time: 170 Days and 4.8 Hours
Abstract
BACKGROUND

Breast cancer (BC) continues to occupy a leading position in terms of morbidity and mortality from malignant neoplasms among the female population. One of the promising markers associated with BC progression is programmed death ligand 1 (PD-L1). Previously, we investigated PD-L1 expression in BC via a new antibody against programmed cell death protein 1 ligand 1 (PDCD1 LG1) and reported that high PDCD1 LG1 expression in tumor cells is an independent factor for a high risk of regional metastasis in patients with BC. However, the prognostic significance of PDCD1 LG1 expression in BC stromal cells has not been adequately studied.

AIM

To study the features of PDCD1 LG1 expression in BC stromal cells and its relationship with BC clinicopathological characteristics.

METHODS

In a prospective single-center observational study, tumor samples from 148 patients with newly diagnosed BC were examined. The tumor sections were immunohistochemically stained with antibodies against PDCD1 LG1. In the tumor samples, the PDCD1 LG1-positive lymphocyte (PDCD1 LG1+ LF) score, presence of nuclear PDCD1 LG1 expression in the LFs, PDCD1 LG1 expression in polymorphic cell infiltrates (PDCD1 LG1+ polymorphic cell infiltrates [PCIs]), and cells of the fibroblastic stroma and endothelial cells of the tumor microvessels were assessed. Statistical analyses were performed using Statistica 10.0 software.

RESULTS

A PDCD1 LG1+ LF score ≥ 3 was detected more often at stages N0 and N3 than at N1 and N2 (P = 0.03). Moderate and pronounced PDCD1 LG1+ PCIs and the presence of PDCD1 LG1+ fibroblastic stroma were associated with negative estrogen receptor status (P = 0.0008 and P = 0.03, respectively), human epidermal growth factor receptor 2-positive (HER2+) BC (P < 0.00001 and P = 0.0005), and luminal B HER2+, non-luminal HER2+ and triple-negative BC (P < 0.00001 and P = 0.004). The risk of metastasis to regional lymph nodes (RLNs) depend on lymphovascular invasion (LVI) and the PDCD1 LG1+ LF score. In the absence of LVI and a PDCD1 LG1+ LF score < 3 or ≥ 3, metastases in RLNs were absent in 66.6% and 93.9% of patients with BC, respectively. In the presence of LVI and a PDCD1 LG1+ LF score < 3 or ≥ 3, metastases in RLNs were detected in 82.6% and 92.7% of patients with BC, respectively.

CONCLUSION

The results indicated that the combined assessment of the PDCD1 LG1+ LF score and LVI can improve the accuracy of predicting the risk of metastasis to RLNs in patients with BC.

Keywords: Breast cancer; Programmed death-ligand 1; Regional metastasis; Tumor stroma

Core Tip: Programmed death ligand 1 expression was studied in breast cancer (BC) stromal cells using a new antibody against programmed cell death protein 1 ligand 1 (PDCD1 LG1). This study revealed that moderate and pronounced PDCD1 LG1 expression in polymorphic cell infiltrates and the presence of PDCD1 LG1 expression in the fibroblastic stroma are associated with unfavorable BC prognosis. Additionally, PDCD1 LG1+ lymphocyte score ≥ 3 in the absence of lymphovascular invasion (LVI) is associated with a reduced risk of BC regional metastasis; by contrast, in the presence of LVI, it is associated with an increased risk of regional BC metastasis.