Volume 78, October 2025, 152481Author links open overlay panel, , , , , , AbstractObjective

Research on the expression of PD-L1 (clone SP263) in prostate cancer (PC) is rare. This study aims to investigate PD-L1 (SP263) expression and its clinicopathological correlations in PC.

Methods

A total of 265 PC samples at our center from 2021 to 2024 were included in this study. The clinical information and pathological data were collected. Whole-slide immunohistochemical analysis of PD-L1 (SP263), p53, ERG, PTEN, HER-2 and Ki67 was performed on PC samples, including core biopsies, radical prostatectomies, transurethral resections of the prostate and metastases. Next-generation sequencing was performed in 17 patients and the status of TP53, BRCA1/2 were analyzed. Associations were assessed between PD-L1 status and clinicopathological parameters (age, preoperative serum prostate-specific antigen [PSA], surgical margin, Gleason Group [GG], TNM stage, Ki-67, p53/TP53, BRCA1/2, survival outcomes, etc.) using chi-square, Mann-Whitney U and Kaplan-Meier analyses.

Results

PD-L1 positivity (10.2 %, 27/265) correlated with advanced age (P = 0.007), high GG (P = 0.019), T3/4 stage (P = 0.001), positive surgical margin (P = 0.004), aberrant p53/TP53 (P = 0.043), and elevated Ki-67 (P = 0.042). No associations were observed between these factors (serum PSA, N category, M category, PTEN, ERG, BRCA1/2, or survival outcomes) and PD - L1.

Conclusion

The expression of PD-L1 (SP263) is positively associated with pathologically aggressive parameters in PC. This finding implies the potential value of PD-L1 as a biomarker for risk stratification. Moreover, it indicates the possibility of using PD-L1 (SP263) and p53 expression to guide the combinational application of mutated p53 inhibitors and PD-1/PD-L1 antibodies in PC.

Introduction

Prostate cancer (PC) is the most common cancer and remains the second leading cause of cancer deaths in men in the United States [1]. Although surgical or chemical castration can initially be effective in delaying disease progression and contribute to a favorable outcome, some patients eventually develop castration-resistant prostate cancer (CRPC) and have an adverse prognosis. New treatment strategies are urgently needed in this population. Programmed death-ligand 1 (PD-L1), a transmembrane protein expressed on both neoplastic cells and tumor-infiltrating immune cells, plays a dual regulatory role in tumorigenesis by promoting immune escape. The 2023 United States National Comprehensive Cancer Network (NCCN) guidelines have allowed the use of pembrolizumab in patients with microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) metastatic CRPC whose disease has progressed through docetaxel and a novel hormone therapy [1].

Despite the established role of PD-L1 as a predictive biomarker for immune checkpoint inhibitors in multiple malignancies, the relationship between its expression pattern and clinicopathological parameters in PC is remain poorly characterized. Existing studies predominantly utilize tissue microarrays (TMAs) or small cohorts, with significant variability across PD-L1 clones (e.g., 22C3, SP142). These limitations are particularly pronounced in the SP263 clone, which has been clinically validated for urothelial carcinoma [2].

This study represents the largest analysis to date evaluating PD-L1 (SP263) expression in non-TMA PC specimens and its clinicopathological correlations and prognostic implications.

Section snippetsPatients and tissue samples

Two hundred and forty-two patients and 265 samples were obtained retrospectively from different types of specimens of PC, including prostate core biopsies (n = 123), radical prostatectomies (RPs, n = 129), transurethral resections of the prostate (TURPs, n = 5), and metastases (n = 8) from 2021 to 2024 accessioned by Department of Pathology, Fuzhou University Affiliated Provincial Hospital in current series. Of these, 23 patients included core biopsies and radical treatment specimens. The

PD-L1 expression in different specimen-types of PC

Among all PC specimens, 27 out of 265 (10.2 %) had a TC proportion of at least 1%. Specifically, in this group, 17 (6.4 %) had a TC proportion ranging from 1% to less than 5%, 4 (1.5 %) had a proportion from 5% to less than 10%, and 6 (2.3 %) had a proportion from 10% to less than 25%. For immune cells, 2/265 (0.8 %) had an IC proportion > 1 %, 57/265 (21.5 %) had an ICP > 1 %, and 1/265 (0.4 %) had an IC+ > 25 %, details can be found in Supplementary Table S2 (Fig. 1). Although the ICP were

Discussion

Prostate cancer is an immunological “cold” tumor, and there are few studies in the field of immune checkpoint inhibitors such as PD-L1, and some conclusions are still controversial. To our knowledge, this is the first large non-TME sample study to explore the expression of PD-L1 (clone SP263) in PC and the clinic–pathologic correlations between PD-L1 and PC. All previous studies of SP263 clones in PC were either TME samples [[6], [7], [8], [9]] or small sample size studies [10,11]. Besides,

Conclusion

Our large-scale immunohistochemical analysis establishes PD-L1 (SP263) expression as a hallmark of pathologically aggressive PC, demonstrating robust correlations with adverse pathological features—elevated GG, advanced T stage, positive surgical margin, and proliferative phenotypes. Notably, the novel association between PD-L1 and p53/TP53 aberrations provides mechanistic rationale for dual targeting of immune evasion and deficient DNA repair/genomic instability pathways.

CRediT authorship contribution statement

Xiaopeng Zhuang: Methodology, Writing – original draft, Project administration. Huiting Li: Data curation. Zhijie You: Investigation. Hui Cheng: Investigation. Guodong Guo: Investigation. Xin Chen: Resources. Haijian Huang: Methodology, Writing – review & editing.

Declaration of competing interest

None of the authors of this manuscript have any conflict of interest to declare. In addition, this work was funded by grants from the Startup Fund for scientific research, Fujian Medical University, China (grant number 2021QH1310).

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