Programmed Death Ligand 1 (PD-L1) Expression and its Association with Driver Mutations among Patients with Non-Small Cell Lung Cancer in a Private Tertiary Care Setting
DOI:
https://doi.org/10.21141/10.21141/PJP.2022.17Keywords:
non-small cell lung cancer, programmed death ligand 1, PD-L1, driver mutationAbstract
Objective. The advent of immunotherapy has significantly changed the treatment and management of patients with advanced non-small cell lung cancer (NSCLC). Prior to initiation of immunotherapy,
evaluation of programmed death ligand 1 (PD-L1) expression is required. One factor that affects PD-L1 expression in NSCLC is the presence of oncogenic driver mutations; however, little data on its
association is available, especially in the Philippine setting. The study aims to determine the prevalence of PD-L1 expression and its association with driver mutations among patients with non-small cell lung cancer in a private tertiary care hospital in the Philippines.
Methodology. The study was undertaken for a period of two years from July 2017-July 2019 at St. Luke’s Medical Center and included 446 NSCLC samples. PD-L1 was evaluated by immunohistochemistry using 22C3 anti-PD-L1 antibody clone, EnVision FLEX visualization system on Autostainer Link 48. Patient demographics and data on driver mutation testing were recorded. Statistical analysis was performed using logistic regression.
Results. PD-L1 expression was observed in 273 (61.20%) of 446 cases, 119 (61.20%) of which
demonstrated high PD-L1 expression while 154 (34.50%) had low PD-L1 expression. There was no
significant association between PD-L1 expression and EGFR mutation, ALK mutation, age, and gender.
For histologic type, high PD-L1 expression was significantly associated with adenocarcinoma and non-
small cell carcinoma, NOS.
Conclusion. The overall prevalence of PD-L1 expression in non-small cell lung carcinoma is 61.20%
based on the cases included. Although we did not find an association between PD-L1 expression and
EGFR and ALK mutation, our study observed that ALK-mutated NSCLCs have 4.7 odds of having high
PD-L1 expression, however, a higher sample size is warranted to truly determine significant association. The outcome of this study may provide help in the stratification of patients and predict those who will benefit from immunotherapy.
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6. Garon EB, Rizvi NA, Leighl N, et al. Pembrolizumab for the treatment of non-small cell lung cancer. N Engl J Med. 2015;372(21):2018-28. https://pubmed.ncbi.nlm.nih.gov/25891174.https://doi.org/10.1056/NEJMoa1501824.
7. Teixidó C, Vilariño N, Reyes R, Reguart N. PD-L1 expression testing in non-small cell lung cancer. Ther Adv Med Oncol. 2018;10:1758835918763493. https://pubmed.ncbi.nlm.nih.gov/29662547. PMCID:PMC5898658. https://doi.org/10.1177/1758835918763493.
8. Hunter KA, Socinski MA, Villaruz LC. PD-L1 testing in guiding patient selection for PD-1/PD-L1 inhibitor therapy in lung cancer. Mol Diagn Ther. 2018;22(1):1-10. https://pubmed.ncbi.nlm.nih.gov/29119407 PMCID:PMC5773410 DOI: 10.1007/s40291-017-0308-6.
9. Kim H, Chung JH. PD-L1 Testing in non-small cell lung cancer: past, present, and future. J Pathol Transl Med. 2019;53(4):199-206. https://pubmed.ncbi.nlm.nih.gov/31042863. PMCID: PMC6639705. https://doi.org/10.4132/jptm.2019.04.24.
10. Stratton MR, Campbell PJ, Futreal PA. The cancer genome. 2009;458(7239):719-24. https://pubmed.ncbi.nlm.nih.gov/19360079 PMCID: PMC2821689. https://doi.org/10.1038/nature07943.
11. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology Version 3.2020. Non-small cell lung cancer. https://www2.tri-kobe.org/nccn/guideline/lung/english/non_small.pdf. Accessed November 11, 2019.
12. Song Z, Yu X, Cheng G, Zhang Y. Programmed death-ligand 1 expression associated with molecular characteristic in surgically resected lung adenocarcinoma. J Transl Med. 2016;14(1):188. https://pubmed.ncbi.nlm.nih.gov/27342566. PMCID: PMC4919857. https://doi.org/10.1186/s12967-016-0943-4.
13. El-Telbany A, Ma PC. Cancer genes in lung cancer racial disparities: are there any? Genes Cancer. 2012; 3(7-8):467–80. https://pubmed.ncbi.nlm.nih.gov/23264847. PMCID: PMC3527990. https://doi.org/10.1177/1947601912465177.
14. Hirsch FR, Varella-Garcia M, Bunn PA Jr, et al. Epidermal growth factor receptor in non-small-cell lung carcinomas: correlation between gene copy number and protein expression and impact on prognosis. J Clin Oncol. 2003;21(20):3798-807. https://pubmed.ncbi.nlm.nih.gov/12953099. https://doi.org/10.1200/JCO.2003.11.069.
15. Nee-Estuye-Evangelista CK, Andal JL, Ang DC. Frequency of epidermal growth factor receptor mutations among filipino patients with non-small cell lung carcinoma. Philipp J Pathol. 2018;3(1):6-11. https://doi.org/10.21141/PJP.2018.002.
16. Merker JD, Oxnard GR, Compton C, et al. Circulating tumor DNA analysis in patients with cancer: American Society of Clinical Oncology and College of American Pathologists Joint Review. J Clin Oncol. 2018;36(16):1631-41. https://pubmed.ncbi.nlm.nih.gov/29504847. https://doi.org/10.1200/JCO.2017.76.8671.
17. Shaw AT, Solomon B. UpToDate. 2019. Anaplastic lymphoma kinase (ALK) fusion oncogene positive in non-small cell lung cancer. https://www.uptodate.com/contents/anaplastic-lymphoma-kinase-alk-fusion-oncogene-positive-non-small-cell-lung-cancer#H1. Accessed November 11, 2019.
18. Vijayalkshmi R, Krishnamurthy A. Targetable “driver” mutations in non-small cell lung cancer. Indian J Surg Oncol. 2011; 2(3):178–88. https://pubmed.ncbi.nlm.nih.gov/22942608. PMCID: PMC3272176. https://doi.org/10.1007/s13193-011-0108-0.
19. Rimkunas VM, Crosby KE, Li D, et al. Analysis of receptor tyrosine kinase ROS1-positive tumors in non-small cell lung cancer: identification of a FIG-ROS1 fusion. Clin Cancer Res.2012;18(16):4449-57. https://pubmed.ncbi.nlm.nih.gov/22661537. https://doi.org/10.1158/1078-0432.CCR-11-3351.
20. Bergethon K, Shaw AT, Ou SH, et al. ROS1 rearrangements define a unique molecular class of lung cancers. J Clin Oncol. 2012;30(8):863-70. https://pubmed.ncbi.nlm.nih.gov/22215748. PMCID: PMC3295572. https://doi.org/10.1200/JCO.2011.35.6345.
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12/28/2022
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Pua, M. J., Santiago, R. M. ., Andal, J. J., & Ang, D. . (2022). Programmed Death Ligand 1 (PD-L1) Expression and its Association with Driver Mutations among Patients with Non-Small Cell Lung Cancer in a Private Tertiary Care Setting. PJP, 7(2), 36–45. https://doi.org/10.21141/10.21141/PJP.2022.17
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