Immunohistochemical Expression of Programmed Death Ligand-1 (PD-L1) in Gastric Adenocarcinoma and Non-Neoplastic Gastric Epithelium

Authors

  • Shah Faisal Peshawar Medical College, Riphah International University, Islamabad,Pakistan.
  • Fozia Rauf Peshawar Medical College, Riphah International University, Islamabad,Pakistan.
  • Danyal Khan Peshawar Medical College, Riphah International University, Islamabad,Pakistan. https://orcid.org/0000-0002-5643-5818
  • Saria Saeed Ali Peshawar Medical College, Riphah International University, Islamabad,Pakistan. https://orcid.org/0009-0006-1468-760X
  • Muhammad Tayyab Kuwait Teaching Hospital, Peshawar Medical College, Riphah International University, Islamabad,Pakistan.
  • Natasha Kamran Peshawar Dental College, Riphah International University, Islamabad,Pakistan. https://orcid.org/0009-0003-4082-7686

DOI:

https://doi.org/10.36283/ziun-pjmd14-4/086

Keywords:

Gastric Neoplasms, Adenocarcinoma, Programmed Death-Ligand 1, Immunohistochemistry, Biomarkers

Abstract

Background: Tumor progression is heavily influenced by immune evasion strategies such as the expression of Programmed Death Ligand-1 (PD-L1), which also presents as a promising target for cancer therapies. This study aimed to investigate the immunohistochemical presence of PD-L1 in gastric adenocarcinoma tissues and to compare it with non-cancerous gastric mucosa, and explore its relationship with various clinicopathological factors.

Methods: This comparative analytical cross-sectional study was conducted at the Histopathology Division, Department of Pathology, Peshawar Medical College, Riphah International University, Islamabad, over one year (March 2022–February 2023). A total of 60 formalin-fixed, paraffin-embedded (FFPE) samples were analyzed, comprising 30 gastric adenocarcinoma specimens from gastrectomies and 30 non-neoplastic gastric mucosa samples from endoscopic biopsies. Samples were selected using non-probability consecutive sampling. PD-L1 expression was assessed by standardized immunohistochemistry, scored for intensity and proportion of positive cells, and reviewed independently by two pathologists. Statistical analysis was performed using SPSS version 20.0; Chi-square and Fisher’s exact tests were applied, with p < 0.05 considered significant. Although a smaller comparison group (e.g., 2:1 ratio) could suffice to demonstrate absence of PD-L1 in non-neoplastic tissue, an equal ratio (1:1) was chosen to strengthen comparability and analysis.

Results: PD-L1 expression was detected more frequently in 14 out of 30 neoplastic gastric tissues (46.6%) compared to 2 out of 30 non-neoplastic samples (6.6%), although this difference was not statistically significant (p=0.171). No significant associations were found between PD-L1 expression and patient age, sex, tumor location, histological subtype, tumor grade, stage, lymph node involvement, or presence of perineural or vascular invasion.

Conclusion: PD-L1 is commonly expressed in gastric adenocarcinoma; however, its expression does not appear to be significantly linked to major clinicopathological characteristics. Multicenter studies with larger study population are warranted to better understand the prognostic value and therapeutic potential of PD-L1 in gastric cancer.

Author Biographies

  • Shah Faisal, Peshawar Medical College, Riphah International University, Islamabad,Pakistan.

    Department of Pathology and Lecturer,

  • Fozia Rauf, Peshawar Medical College, Riphah International University, Islamabad,Pakistan.

    Department of Pathology and Professor,

  • Danyal Khan, Peshawar Medical College, Riphah International University, Islamabad,Pakistan.

    Department of Pathology and Lecturer,

  • Saria Saeed Ali, Peshawar Medical College, Riphah International University, Islamabad,Pakistan.

    Department of Pathology and Lecturer,

  • Muhammad Tayyab, Kuwait Teaching Hospital, Peshawar Medical College, Riphah International University, Islamabad,Pakistan.

     Department of Surgery and Professor ,

  • Natasha Kamran, Peshawar Dental College, Riphah International University, Islamabad,Pakistan.

    Department of Oral Pathology and Lecturer,

References

1. Smyth EC, Nilsson M, Grabsch HI, van Grieken NC, Lordick F. Gastric cancer. The Lancet. 2020;396(10251):635-48.

2. Lin JL, Lin JX, Lin GT, Huang CM, Zheng CH, Xie JW, Wang JB, Lu J, Chen QY, Li P. Global incidence and mortality trends of gastric cancer and predicted mortality of gastric cancer by 2035. BMC Public Health. 2024 Jul 2;24(1):1763. doi: 10.1186/s12889-024-19104-6.

3. Thrift AP, El-Serag HB. Burden of gastric cancer. Clinical gastroenterology and hepatology. 2020;18(3):534-42.

4. Zhu X, Pigazzi A, Zell J, Lu Y. Changing disparity of gastric cancer incidence by histological types in US race-specific populations. Cancer Control. 2020;27(1):1073274820977152.

5. López MJ, Carbajal J, Alfaro AL, Saravia LG, Zanabria D, Araujo JM, et al. Characteristics of gastric cancer around the world. Critical Reviews in Oncology/Hematology. 2023;181:103841.

6. Sheikh S, Rana S, Wani HA, Ali A, Sehar N, Majid S, et al. Gastric Cancer and Genetic Polymorphisms in Modulating the Susceptibility. Genetic Polymorphism and Disease: CRC Press; 2022. p. 477-94.

7. Ilic M, Ilic I. Epidemiology of stomach cancer. World journal of gastroenterology. 2022;28(12):1187.

8. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians. 2021;71(3):209-49.

9. Amjad S, Saleem M, Ashraf A, Iqbal MN. Prevalence of Cancer Types in Patients attending Mayo Hospital Lahore, Pakistan. International Journal of Molecular Microbiology. 2020;3(2):25-34.

10. Liang Y, Zhao L, Chen H, Lin T, Chen T, Zhao M, et al. Survival analysis of elderly patients over 65 years old with stage II/III gastric cancer treated with adjuvant chemotherapy after laparoscopic D2 gastrectomy: a retrospective cohort study. BMC cancer. 2021;21:1-12.

11. Li Y, Feng A, Zheng S, Chen C, Lyu J. Recent estimates and predictions of 5-year survival in patients with gastric cancer: a model-based period analysis. Cancer control. 2022;29. doi: 10732748221099227.

12. Morgan E, Arnold M, Camargo MC, Gini A, Kunzmann AT, Matsuda T, et al. The current and future incidence and mortality of gastric cancer in 185 countries, 2020–40: a population-based modelling study. EClinicalMedicine. 2022;47.

13. Li J, Kuang X, Zhang Y, Hu D, Liu K. Global burden of gastric cancer in adolescents and young adults: estimates from GLOBOCAN 2020. Public Health. 2022;210:58-64.

14. Shore R. Sex hormones in gastric mucosal physiology and the development of oesophageal, gastric and colorectal adenocarcinoma. Karolinska Institutet (Sweden); 2022. https://openarchive.ki.se/articles/thesis/Sex_hormones_in_gastric_mucosal_physiology_and_the_development_of_oesophageal_gastric_and_colorectal_adenocarcinoma/26913235?file=48957271

15. Program NT. Helicobacter pylori (Chronic Infection). 15th Report on Carcinogens: National Toxicology Program; 2021.

16. Yu X, Hu F, Li C, Yao Q, Zhang H, Xue Y. Clinicopathologic characteristics and prognosis of proximal and distal gastric cancer. OncoTargets and therapy. 2018:1037-44.

17. Ma J, Li J, Qian M, Han W, Tian M, Li Z, Wang Z, He S, Wu K. PD-L1 expression and the prognostic significance in gastric cancer: a retrospective comparison of three PD-L1 antibody clones (SP142, 28–8 and E1L3N). Diagnostic Pathology. 2018;13:91. doi:10.1186/s13000-018-0766-0.

18. Chen XJ, Wei CZ, Lin J, Zhang RP, Chen GM, Li YF, Nie RC, Chen YM. Prognostic significance of PD-L1 expression in gastric cancer patients with peritoneal metastasis. Biomedicines. 2023;11(7):2003. doi:10.3390/biomedicines11072003.

19. Hirai M, Kitahara H, Kobayashi Y, Kato K, Bou-Gharios G, Nakamura H, Kawashiri S. Regulation of PD-L1 expression in a high-grade invasive human oral squamous cell carcinoma microenvironment. International journal of oncology. 2017 Jan 1;50(1):41-8.

20. Benassai G, Calemma F, Miletti A, Furino E, De Palma GD, Quarto G. Surgical treatment in late-stage gastric cancer. A retrospective analysis of 26 cases. Annali Italiani di Chirurgia. 2021;92(1):20-7.

21. Zhuo W, Liu Y, Li S, Guo D, Sun Q, Jin J, et al. Long noncoding RNA GMAN, up-regulated in gastric cancer tissues, is associated with metastasis in patients and promotes translation of ephrin A1 by competitively binding GMAN-AS. Gastroenterology. 2019;156(3):676-91. e11.

22. Kemal G, Seker D, Hülya Ö. Determination of erythrocyte Glutathione S-Transferase activity in individuals with gastric and colon cancer. GSC Biological and Pharmaceutical Sciences. 2022;20(3):192-7.

23. Bergquist JR, Leiting JL, Habermann EB, Cleary SP, Kendrick ML, Smoot RL, et al. Early-onset gastric cancer is a distinct disease with worrisome trends and oncogenic features. Surgery. 2019;166(4):547-55.

24. Rajadurai P, Yap NY, Chiew SF, Zin RR, Pauzi SH, Jaafar AS, Yahaya A, Looi LM. Prevalence of Programmed Death-Ligand 1 Positivity Using SP142 in Patients With Advanced Stage Triple-Negative Breast Cancer in Malaysia: A Cross-Sectional Study. Journal of Breast Cancer. 2024 Nov 25;27(6):362. doi: https://doi.org/10.4048/jbc.2024.0040

25. Hiss S, Eckstein M, Segschneider P, Mantsopoulos K, Iro H, Hartmann A, et al. Tumour-infiltrating lymphocytes (TILs) and PD-L1 expression correlate with lymph node metastasis, high-grade transformation and shorter metastasis-free survival in patients with acinic cell carcinoma (AciCC) of the salivary glands. Cancers. 2021;13(5):965.

26. Andrianto A, Rudiman R, Ruchimat T, Lukman K, Sulthana BAAS, Purnama A, Wijaya A, Primastari E, Nugraha P. Association of PD-L1 Expression with Lymph Node Metastasis and Clinical Stage in Ampulla of Vater Cancer: An Observational Study. Cancer Manag Res. 2025 May 13;17:965-974. doi: 10.2147/CMAR.S513961.

27. Jovanović L, Janković R, Ćirković A, Jović M, Janjić T, Djuričić S, Milenković S. PD-L1 Expression in Different Segments and Histological Types of Ovarian Cancer According to Lymphocytic Infiltrate. Medicina (Kaunas). 2021 Nov 29;57(12):1309. doi: 10.3390/medicina57121309

Downloads

Published

2025-09-29

Metrics

How to Cite

1.
Faisal S, Rauf F, Khan D, Ali SS, Tayyab M, Kamran N. Immunohistochemical Expression of Programmed Death Ligand-1 (PD-L1) in Gastric Adenocarcinoma and Non-Neoplastic Gastric Epithelium. PJMD [Internet]. 2025 Sep. 29 [cited 2026 Jun. 3];14(4). Available from: https://ojs.zu.edu.pk/pjmd/article/view/4195

Similar Articles

21-30 of 273

You may also start an advanced similarity search for this article.