Programmed Death Ligand 1 (PD-L1) Expression and its Association with Clinicopathologic Profile in Patients with Non-Small Cell Lung Cancer in a Philippine Tertiary Medical Center
DOI:
https://doi.org/10.21141/PJP.2021.08Keywords:
non-small cell lung cancer, lung cancer, PD-L1, PhilippinesAbstract
Introduction. The current management of advanced non-small cell lung cancer (NSCLC) includes the characterization of Programmed Death Ligand-1 (PD-L1) expression for potential immune checkpoint inhibitor treatment. There is currently no available data regarding the patterns of PD-L1 expression in NSCLC, as well as their association with clinicopathologic profile in Filipino patients.
Methodology. Clinicopathologic characteristics of 187 consecutive NSCLC clinical samples with PD-L1 testing using the clone 22C3 pharmaDx kit were collected. The presence of stromal tumor-infiltrating lymphocytes (TILs) were assessed in hematoxylin and eosin-stained slides. PD-L1 expression on tumor cells (TC) and stromal TILs were evaluated.
Results. Of the 187 cases, there were 112 males and 75 females. The mean age at diagnosis was 66.4 years old (32-92 years old). It is composed of 131 cases of Adenocarcinoma, 15 Squamous cell carcinoma, 4 Adenosquamous carcinoma, 32 Non-small cell carcinoma, not otherwise specified, 3 poorly differentiated malignancy, 1 Large cell carcinoma, and 1 Mucinous carcinoma. Specimen types included 17 pleural fluid cell blocks, 60 tumor cell block samples, and 110 tissue biopsies. Tumor cell PD-L1 expression was identified in 59.1% of the 110 tissue biopsies. PD-L1 TPS for histologic specimens are as follows: TPS >50%, TPS 1-49%, and TPS <1% were observed in 23.6%, 35.5%, and 40.9% in our lung cancer cohort, respectively. Of the 77 cytology specimens, 50.6% presented with TC PD-L1 expression. TPS for this subgroup include: 49.4% with no PD-L1 expression, 35.1% with low PD-L1 expression, and 15.6% showing high PD-L1 expression. PD-L1 expression on TC did not correlate with age, sex, or histology for both specimen type subgroups. Stromal tumor-infiltrating lymphocytes were noted in 74.5% of tissue biopsies. Tumor cell block samples did not demonstrate stromal TILs. For tissue biopsies, female gender and TPS 1-49% were more likely to have <50% PD-L1 expression on TILs.
Conclusion. Overall TC PD-L1 expression was observed in more than half (55.6%) of NSCLC patients in our cohort. The prognostic value of PD-L1 and clinical response to immune checkpoint inhibitors in the Filipino population needs to be further investigated.
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References
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2. Laudico AV, Mirasol-Lumague MR, Medina V, Mapua CA, Valenzuela FG, Pukkala E. 2015 Philippine Cancer Facts and Estimates.
3. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology. Non-Small Cell Lung Cancer. Version 8.2020. September 15, 2020. Retrieved from https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf.
4. Travis WD, Brambilla E, Burke AP, Marx A, Nicholson AG. WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart. Lyon: International Agency for Research on Cancer; 2015.
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6. El-Guindy DM, Helal DS, Sabry NM, Abo El-Nasr M. Programmed cell death ligand-1 (PD-L1) expression combined with CD8 tumor infiltrating lymphocytes density in non-small cell lung cancer patients. J Egypt Natl Canc Inst. 2018;30(4):125-31. https://pubmed.ncbi.nlm.nih.gov/
30337185. https://doi.org/10.1016/j.jnci.2018.08.003.
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8. Patel SP, Kurzrock R. PD-L1 expression as a predictive biomarker in cancer immunotherapy. Mol Cancer Ther. 2015;14(4):847-56. https://pubmed.ncbi.nlm.nih.gov/25695955. https://doi.org/10.1158/1535-7163.MCT-14-0983.
9. Del C Monroig-Bosque P, Driver B, Morales-Rosado JA, et al. Correlation between programmed death receptor-1 expression in tumor-infiltrating lymphocytes and programmed death ligand-1 expression in non-small cell lung carcinoma. Arch Pathol Lab Med. 2018;142(11):1388-93. https://pubmed.ncbi.nlm.nih.gov/ 29431467. https://doi.org/10.5858/arpa.2017-0516-OA.
10. Gong X, Li X, Jiang T, et al. Combined radiotherapy and anti–PD-L1 antibody synergistically enhances antitumor effect in non–small cell lung cancer. J Thorac Oncol. 2017;12(7):1085-97. https://pubmed.ncbi.nlm.nih.gov/28478231. https://doi.org/10.1016/j.jtho.2017.04.014.
11. Ohaegbulam KC, Assal A, Lazar-Molnar E, Yao Y, Zang X. Human cancer immunotherapy with antibodies to the PD-1 and PD-L1 pathway. Trends Mol Med. 2015;21(1):24-33. https://pubmed.ncbi.nlm.nih.gov/25440090. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4282825. https://doi.org/10.1016/j.molmed.2014.10.009.
12. Akinleye A, Rasool Z. Immune checkpoint inhibitors of PD-L1 as cancer therapeutics. J Hematol Oncol. 2019;12(1):92. https://pubmed.ncbi.nlm.nih.gov/31488176. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6729004. https://doi.org/10.1186/s13045-019-0779-5.
13. Somasundaram A, Burns TF. Pembrolizumab in the treatment of metastatic non-small-cell lung cancer: patient selection and perspectives. Lung Cancer (Auckl). 2017;8:1-11. https://pubmed.ncbi.nlm.nih.gov/28293123. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5342609. https://doi.org/10.2147/LCTT.S105678.
14. Badalamenti G, Fanale D, Incorvaia L, et al. Role of tumor-infiltrating lymphocytes in patients with solid tumors: Can a drop dig a stone?. Cell Immunol. 2019;343:103753. https://pubmed.ncbi.nlm.nih.gov/29395859. https://doi.org/10.1016/j.cellimm.2018.01.013.
15. Zhang M, Feng D, Jing J, Liu H, Zhao S, Zhang Q. PD-L1 protein expression in non-small cell lung cancer based on different immunohistochemical antibodies. J Thorac Dis. 2017;9(5):E470-3. https://pubmed.ncbi.nlm.nih.gov/28616312. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5465173. https://doi.org/10.21037/jtd.2017.04.34.
16. Sorensen SF, Zhou W, Dolled-Filhart M, et al. PD-L1 expression and survival among patients with advanced non-small cell lung cancer treated with chemotherapy. Transl Oncol. 2016;9(1):64-9. https://pubmed.ncbi.nlm.nih.gov/26947883. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4800057. https://doi.org/10.1016/j.tranon.2016.01.003.
17. He Y, Rozeboom L, Rivard CJ, et al. PD-1, PD-L1 protein expression in non-small cell lung cancer and their relationship with tumor-infiltrating lymphocytes. Med Sci Monit. 2017;23:1208-16. https://pubmed.ncbi.nlm.nih.gov/28275222. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356616. https://doi.org/10.12659/msm.899909.
18. Garon EB, Rizvi NA, Hui, R. et al. Pembrolizumab for the treatment of non-small-cell lung cancer. New Engl J Med. 2015:372(1):2018-28. https://pubmed.ncbi.nlm.nih.gov/25891174. https://doi.org/10.1056/NEJMoa1501824.
19. Bubendorf L, Lantuejoul S, de Langen AJ, Thunnissen E, Nonsmall cell lung carcinoma: diagnostic difficulties in small biopsies and cytological specimens: number 2 in the series "Pathology for the clinician" edited by Peter Dorfmüller and Alberto Cavazza. Eur Respir Rev. 2017;26(144):170007. https://pubmed.ncbi.nlm.nih.gov/28659503. https://doi.org/10.1183/16000617.0007-2017.
20. Mino-Kenudson M. Immunohistochemistry for predictive biomarkers in non-small cell lung cancer. Transl Lung Cancer Res. 2017;6(5):570-87. https://pubmed.ncbi.nlm.nih.gov/29114473. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5653529. https://doi.org/10.21037/tlcr.2017.07.06.
21. Kim H, Kwon HJ, Park SY, Park E, Chung JH. PD-L1 immunohistochemical assays for assessment of therapeutic strategies involving immune checkpoint inhibitors in non-small cell lung cancer: a comparative study. Oncotarget. 2017;8(58):98524-32. https://pubmed.ncbi.nlm.nih.gov/29228707. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5716747. https://doi.org/10.18632/oncotarget.21567.
22. Ratcliffe MJ, Sharpe A, Midha A, et al. Agreement between programmed cell death ligand-1 diagnostic assays across multiple protein expression cutoffs in non-small cell lung cancer. Clin Cancer Res. 2017;23(14):3585-91. https://pubmed.ncbi.nlm.nih.gov/28073845. https://doi.org/10.1158/1078-0432.CCR-16-2375.
23. Hirsch FR, McElhinny A, Stanforth D, et al. PD-L1 immunohistochemistry assays for lung cancer: results from phase 1 of the blueprint PD-L1 IHC assay comparison project. J Thorac Oncol. 2017;12(2):208-22. https://pubmed.ncbi.nlm.nih.gov/27913228. https://doi.org/10.1016/j.jtho.2016.11.2228.
24. Tsao MS, Kerr KM, Kockx M, et al. PD-L1 immunohistochemistry comparability study in real-life clinical samples: results of blueprint phase 2 project. J Thorac Oncol. 2018;13(9):1302-11. https://pubmed.ncbi.nlm.nih.gov/29800747. https://doi.org/10.1016/j.jtho.2018.05.013.
25. Stoy SP, Rosen L, Mueller J, Murgu S. Programmed death‐ligand 1 testing of lung cancer cytology specimens obtained with bronchoscopy. Cancer Cytopathol. 2018;126(2):122-8. https://pubmed.ncbi.nlm.nih.gov/29053224. https://doi.org/10.1002/cncy.21941.
26. Yu H, Boyle TA, Zhou C, Rimm DL, Hirsch FR. PD-L1 expression in lung cancer. J Thorac Oncol. 2016;11(7):964-75. https://pubmed.ncbi.nlm.nih.gov/27117833. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5353357. https://doi.org/10.1016/j.jtho.2016.04.014.
27. Gandhi L, Rodríguez-Abreu D, Gadgeel S, et al. Pembrolizumab plus chemotherapy in metastatic non–small-cell lung cancer. N Engl J Med. 2018;378:2078-92. https://pubmed.ncbi.nlm.nih.gov/29658856. https://doi.org/10.1056/NEJMoa1801005.
28. Herbst RS, Baas P, Kim DW, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2016;387(10027):1540-50. https://pubmed.ncbi.nlm.nih.gov/26712084. https://doi.org/10.1016/S0140-6736(15)01281-7.
29. Reck M, Rodríguez-Abreu D, Robinson AG, et al. Pembrolizumab versus chemotherapy for PD-L1–positive non–small-cell lung cancer. N Engl J Med, 2016;375:1823-33. https://pubmed.ncbi.nlm.nih.gov/27718847. https://doi.org/10.1056/NEJMoa1606774.
30. Lin G, Fan X, Zhu W, et al. Prognostic significance of PD-L1 expression and tumor infiltrating lymphocyte in surgically resectable non-small cell lung cancer. Oncotarget. 2017;8(48):83986-94. https://pubmed.ncbi.nlm.nih.gov/29137398. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5663570. https://doi.org/10.18632/oncotarget.20233.
31. Herbst R, Giaccone G, de Marinis F, et al. Atezolizumab for first-line treatment of PD-L1 selected patients with NSCLC. N Engl J Med. 2020;383(14):1328-39. https://pubmed.ncbi.nlm.nih.gov/32997907. https://doi.org/10.1056/NEJMoa1917346.
32. Sun JM, Zhou W, Choi YL, et al. Prognostic significance of PD-L1 in patients with non–small cell lung cancer: a large cohort study of surgically resected cases. J Thorac Oncol. 2016;11(7):1003-11. https://pubmed.ncbi.nlm.nih.gov/27103510. https://doi.org/10.1016/j.jtho.2016.04.007.
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Published
06/27/2021
How to Cite
Sta. Ines, F. M., Andal, J. J., Santiago, R. M., Sandoval, S., & Ang, D. (2021). Programmed Death Ligand 1 (PD-L1) Expression and its Association with Clinicopathologic Profile in Patients with Non-Small Cell Lung Cancer in a Philippine Tertiary Medical Center. PJP, 6(1), 8–17. https://doi.org/10.21141/PJP.2021.08
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