Programmed Death Ligand-1 Expression in Gastric Cancer Cases in Zambia

Husna Munshi; Chibamba Mumba; Mupeta Songwe; Violet Kayamba

doi:10.53974/unza.jabs.9.2.1492

Husna Munshi Department of Pathology and Microbiology, University of Zambia School of Medicine, Lusaka, Zambia.
Chibamba Mumba Tropical Gastroenterology & Nutrition group, Lusaka, Zambia
Mupeta Songwe Department of Pathology and Microbiology, University Teaching Hospital, Lusaka, Zambia
Violet Kayamba Department of Internal Medicine, University of Zambia School of Medicine, Lusaka Zambia

DOI: https://doi.org/10.53974/unza.jabs.9.2.1492

Keywords: Gastric Cancer, Adenocarcinoma, Immunohistochemistry, Programmed Death Ligand-1, Immunotherapy, Zambia

Abstract

Gastric cancer is a highly fatal disease in Zambia due to delayed diagnosis, aggressiveness of the disease and ineffective treatment. Programmed death ligand-1 is a key biomarker of gastric cancer, linked to immune evasion and response to anti- Programmed death ligand-1 therapies. This study aimed to evaluate the expression of in gastric cancer cases and its association with various clinicopathological prognostic factors in Zambia. This pilot study utilized archived formalin-fixed, paraffin-embedded tissue blocks from patients diagnosed with gastric cancer at the University Teaching Hospitals in Lusaka, Zambia. A total of 41 gastric cancer samples were examined, with 65.9% female (27) and 34.1% male (14), and a median age of 63 years (interquatile range: 56–76). The slides were stained with Haematoxylin and Eosin, followed by immunohistochemical analysis to assess Programmed Death Ligand-1 expression, which was evaluated using a combined positive scoring system. Statistical analysis was conducted using STATA, version 15. Six patients (14.6%) exhibited positive expression of Programmed Death Ligand-1, with a combined positive score of 1 or higher. However, our analysis did not reveal any significant associations between PD-L1 expression and any of the clinicopathological variables assessed. We found that a small proportion (14.6%) of GCs in our population express Programmed Death Ligand-1, identifying a potentially therapeutically actionable patient group.

References

1. Wu Y, Cao D, Qu L, Cao X, Jia Z, Zhao T, et al. PD-1 and PD-L1 co-expression predicts favorable prognosis in gastric cancer. Oncotarget. 2017 Sep 8;8(38):64066–82.
2. Ilic M, Ilic I. Epidemiology of stomach cancer. WJG. 2022 Mar 28;28(12):1187–203.
3. GLOBOCAN 2022. Global cancer statistics 2022; Incidence, Mortality and Prevalence by cancer site [Internet]. WHO; (GLOBOCAN REPORTS). Available from: https://gco.iarc.fr/today/en
4. Asombang AW, Kayamba V, Turner-Moss E, Banda L, Colditz G, Mudenda V, et al. Gastric Malignancy Survival in Zambia, Southern Africa: A Two Year Follow up Study. Med J Zambia. 2014;41(1):13–8.
5. Davis AA, Patel VG. The role of PD-L1 expression as a predictive biomarker: an analysis of all US Food and Drug Administration (FDA) approvals of immune checkpoint inhibitors. j immunotherapy cancer. 2019 Dec;7(1):278.
6. Han Y, Liu D, Li L. PD-1/PD-L1 pathway: current researches in cancer. Am J Cancer Res. 2020;10(3):727–42.
7. Zhang L, Qiu M, Jin Y, Ji J, Li B, Wang X, et al. Programmed cell death ligand 1 (PD-L1) expression on gastric cancer and its relationship with clinicopathologic factors. Int J Clin Exp Pathol. 2015;8(9):11084–91.
8. Böger C, Behrens HM, Mathiak M, Krüger S, Kalthoff H, Röcken C. PD-L1 is an independent prognostic predictor in gastric cancer of Western patients. Oncotarget. 2016 Apr 26;7(17):24269–83.
9. Brar G, Shah MA. The role of pembrolizumab in the treatment of PD-L1 expressing gastric and gastroesophageal junction adenocarcinoma. Therap Adv Gastroenterol. 2019 Jan;12:175628481986976.
10. Mastracci L, Grillo F, Parente P, Gullo I, Campora M, Angerilli V, et al. PD-L1 evaluation in the gastrointestinal tract: from biological rationale to its clinical application. Pathologica. 2022 Oct;114(5):352–64.
11. Gou Q, Dong C, Xu H, Khan B, Jin J, Liu Q, et al. PD-L1 degradation pathway and immunotherapy for cancer. Cell Death Dis. 2020 Nov 6;11(11):955.
12. Park Y, Koh J, Na HY, Kwak Y, Lee KW, Ahn SH, et al. PD-L1 Testing in Gastric Cancer by the Combined Positive Score of the 22C3 PharmDx and SP263 Assay with Clinically Relevant Cut-offs. Cancer Res Treat. 2020 Jul 15;52(3):661–70.
13. Gu L, Huang T, Qiu S, Hong J, Fu R, Ni C, et al. Efficacy of PD-1/PD-L1 inhibitors in patients with advanced gastroesophageal cancer: An updated meta-analysis based on randomized controlled trials. Front Pharmacol. 2022;13:1009254.
14. Yeong J, Lum HYJ, Teo CB, Tan BKJ, Chan YH, Tay RYK, et al. Choice of PD-L1 immunohistochemistry assay influences clinical eligibility for gastric cancer immunotherapy. Gastric Cancer. 2022 Jul;25(4):741–50.
15. Kayamba V, Zyambo K, Mulenga C, Mwakamui S, Tembo MJ, Shibemba A, et al. Biomass Smoke Exposure Is Associated With Gastric Cancer and Probably Mediated Via Oxidative Stress and DNA Damage: A Case-Control Study. JCO Glob Oncol. 2020 Dec 1;(6):532–41.
16. Kim ST, Cristescu R, Bass AJ, Kim KM, Odegaard JI, Kim K, et al. Comprehensive molecular characterization of clinical responses to PD-1 inhibition in metastatic gastric cancer. Nat Med. 2018 Sep;24(9):1449–58.
17. Nshizirungu JP, Bennis S, Mellouki I, Sekal M, Benajah DA, Lahmidani N, et al. Reproduction of the Cancer Genome Atlas (TCGA) and Asian Cancer Research Group (ACRG) Gastric Cancer Molecular Classifications and Their Association with Clinicopathological Characteristics and Overall Survival in Moroccan Patients. Malaguarnera M, editor. Disease Markers. 2021 Jul 28;2021:1–12.
18. Attia S, Abd El Hafez A, Abdel-Aziz A, Elmetwaly S, Mokhtar N. Prognostic Value of PD-L1 Immunohistochemical Marker in Gastric Carcinoma and Its Correlation with HER2 Status. Asian Pac J Cancer Prev. 2022 Apr 1;23(4):1433–44.
19. Sughayer MA, Dabbagh TZ, Battah AH. PD-L1 Expression Is a Favorable Prognostic Marker in Gastric Carcinoma. Applied Immunohistochemistry & Molecular Morphology. 2020 Nov;28(10):748–54.
20. Yamashita K, Iwatsuki M, Harada K, Eto K, Hiyoshi Y, Ishimoto T, et al. Prognostic impacts of the combined positive score and the tumor proportion score for programmed death ligand-1 expression by double immunohistochemical staining in patients with advanced gastric cancer. Gastric Cancer. 2020 Jan;23(1):95–104.
21. Liu X, Choi MG, Kim K, Kim KM, Kim ST, Park SH, et al. High PD-L1 expression in gastric cancer (GC) patients and correlation with molecular features. Pathology - Research and Practice. 2020 Apr;216(4):152881.
22. Derks S, Liao X, Chiaravalli AM, Xu X, Camargo MC, Solcia E, et al. Abundant PD-L1 expression in Epstein-Barr Virus-infected gastric cancers. Oncotarget. 2016 May 31;7(22):32925–32.
23. Marcus L, Lemery SJ, Keegan P, Pazdur R. FDA Approval Summary: Pembrolizumab for the Treatment of Microsatellite Instability-High Solid Tumors. Clinical Cancer Research. 2019 Jul 1;25(13):3753–8.
24. Angell HK, Lee J, Kim KM, Kim K, Kim ST, Park SH, et al. PD-L1 and immune infiltrates are differentially expressed in distinct subgroups of gastric cancer. OncoImmunology. 2019 Feb;8(2):e1544442.
25. Kayamba V, Butt J, Waterboer T, Besa E, Choudhry N, Hamasuku A, et al. Molecular profiling of gastric cancer in a population with high HIV prevalence reveals a shift to MLH1 loss but not the EBV subtype. Cancer Medicine. 2020 May;9(10):3445–54.
26. Schoemig-Markiefka B, Eschbach J, Scheel AH, Pamuk A, Rueschoff J, Zander T, et al. Optimized PD-L1 scoring of gastric cancer. Gastric Cancer. 2021 Sep;24(5):1115–22.
27. Tamura T, Ohira M, Tanaka H, Muguruma K, Toyokawa T, Kubo N, et al. Programmed Death-1 Ligand-1 (PDL1) Expression Is Associated with the Prognosis of Patients with Stage II/III Gastric Cancer. Anticancer Res. 2015 Oct;35(10):5369–76.
28. Geng Y, Wang H, Lu C, Li Q, Xu B, Jiang J, et al. Expression of costimulatory molecules B7-H1, B7-H4 and Foxp3+ Tregs in gastric cancer and its clinical significance. Int J Clin Oncol. 2015 Apr;20(2):273–81.
29. Kwon MJ, Kim KC, Nam ES, Cho SJ, Park HR, Min SK, et al. Programmed death ligand-1 and MET co-expression is a poor prognostic factor in gastric cancers after resection. Oncotarget. 2017 Oct 10;8(47):82399–414.