md-medicaldata

Authors

 

Dragana Tegeltija^1,2, Bosiljka Krajnović², Vanesa Sekeruš^1,2, Goran Stojanović², Bojan Zarić^1,2, Aleksandra Lovrenski^1,2, Dejan Miljković¹, Tijana Vasiljević^1,3, Siniša Maksimović<sup>2

1</sup>Univerzitet u Novom Sadu, Medicinski fakultet Novi Sad, Srbija
²Institut za plućne bolesti Vojvodine, Sremska Kamenica, Srbija
³Institut za onkologiju Vojvodine, Sremska Kamenica, Srbija

 

UDK: 616.24-006.6-07

The paper was received / Rad primljen: 18.05.2021.

Accepted / Rad prihvaćen: 20.05.2021.

 

Correspondence to:

Dragana Tegeltija
Univerzitet u Novom Sadu
Medicinski fakultet Katedra za patologiju,
Hajduk Veljkova 3,
21 000 Novi Sad
e-mail: dragana.tegeltija@mf.uns.ac.rs

 

 

Sažetak

 

 

Uvod: Poslednjih godina tretman sa inhibitorima kontrolnih tačaka ograničen je na pacijente u proširenom stadijumu nemikrocelularnog karcinoma (NSCLC) i visoku ekspresiju PD-L1 određenu imunohistohemijski. Materijal i metode: Retrospektivno je analizirana 223C3-PD-L1 ekpresija kod 204 pacijenta sa NSCLC. Procenat vijabilnih ćelija tumora koji pokazuje parcijalnu ili kompletnu obojenost ćelijske membrane bilo kog intenziteta je skor tumorske proporcije (TPS). PD-L1 status je podeljen u tri grupe: negativan (TPS < 1), slaba ekspresija (TPS 1-49%) i visoka ekspresija (TPS ≥ 50%). Rezultati: 204 pacijenta (123 muškarca i 81 žena), prosečne starosti od 63,76±9,17 godine (od 31 do 86 godina) su bili uključeni u ovu studiju. Najviše pacijenata je bilo u III iIV stadijumu bolesti NSCLC (179; 87,7%) i imali su dobar performans status (199; 97,5%), pozitivnu istoriju pušenja (176; 86,3%) i histologiju  adenokarcinoma (119; 58,3%). TPS je bio negativan u 85/204 (41,7%) pacijenata, 65/20 (31,9%) je pokazivao slabu ekspresiju i 54/204 (26,4%) je imao visoku ekspresiju. Zaključak: Ocena PD-L1 ekspresije u NSCLC detektovana u ovoj studiji je bila slična publikovanim rezultatima.

 

 

 

Ključne reči:

nemikrocelularni karcinom, imunohistohemija, ligand proteina programirane smrti1

 

 

 

Abstract

Background: In recent years, treatment with immune checkpoint inhibitors is limited to patients with advanced stage non-small cell lung cancer (NSCLC) and high tumor expression of programmed death ligand 1 (PD-L1) assessed by immunohistochemistry. Material and Methods:We retrospectively evaluated 22C3-PD-L1 expressions of 204 patients with NSCLC. The percentage of viable tumor cells showing partial or complete membrane staining at any intensity was tumor proportion score (TPS). PD-L1 status was separated in three categories, namely negative (TPS < 1), low expression (TPS 1-49%), and high expression (TPS ≥ 50%). Results: 204 patientes (123 men and 81 women), with an average age of 63,76±9,17 years (from 31 to 86 years) were included in this study. The most of the patients were in III/IV stage NSCLC (179; 87,7%) and had good performance status (199; 97,5%), positive smoking history (176; 86,3%) and adenocarcinoma histology (119; 58,3%). TPS was a negative in 85/204 (41,7%) patients, at 65/204 (31,9%) showed low expression and 54/204 (26,5%) had high expression. Conclusion: The rate of PD-L1 expression of NSCLC detected in this study was similar to the published results.

 

 

Keywords:

non-small cell lung cancer, immunohistochemistry, Programmed cell death-ligand 1

 

 

 

 

References:

1. Liu X, Wang P, Zhang C, Ma Z. Epidermal growth factor receptor (EGFR): A rising star in the era of precision medicine of lung cancer. Oncotarget. 2017;8(30):50209-20.
2. Lemjabbar-Alaoui H, Hassan OU, Yang YW, Buchanan P. Lung cancer: biology and treatment options. Biochim Biophys Acta. 2015;1856(2):189-210.
3. Varela G, Thomas PA. Surgical management of advanced non-small cell lung cancer. J Thorac Dis. 2014;6 Suppl 2:S217-23.
4. Reck M, Heigener DF, Mok T, Soria JC, Rabe KF. Management of non-small cell lung cancer: recent developments. Lancet. 2013;382(9893):709-19.
5. Abernethy AP, Arunachalam A, Burke T, McKay C, Cao X, Sorg R, et al. Real-world first-line treatment and overall survival in non-small lung cancer without known EGFR mutations or ALK rearrangements in US community oncology setting. PLoS One. 2017;12(6):e0178420.
6. Reck M, Rabe KF. Precision diagnosis and treatment in advanced non-small cell lung cancer. N Engl J Med. 2017;377(9):849-61.
7. Juretić A, Bašić Koretić M. Tumor immunotherapy in cilinical setting based on the blockade of molecular interactions of the negative feedback mechanism. Liječ Vijesn. 2017;139:168-72.
8. Brundage MD, Davies D, Mackillop WJ. Prognostic factors in non-small cell lung cancer: a decade of progress. Chest. 2002;122(3):1037-57.
9. Jung CY, Antonia SJ. Tumor immunology and immune checkpoint inhibitors in non-small cell lung cancer. Tuberc Resp Dis. 2018;81(1):29-41.
10. Roach C, Zhang N, Corigliano E, Jansson M, Toland G, Ponto G, et al. Development of a companion diagnostic PD-L1 immunohistochemistry assay for pembrolizumab therapy in non- small-cell lung cancer. Appl Immunohistochem Mol Morphol. 2016;24(6):392-7.
11. He J, Hu Y, Hu M, Li B. Development of PD-1/PD-L1 pathway in tumor immune microenvironment and treatment for non-small cell lung cancer. Sci Rep. 2018;5:13110.
12. Kerr KM, Tsao MS, Nicholson AG, Yatabe Y, Wistuba II, Hirsch FR. Programmed death-ligand 1 immunohistochemistry in lung cancer: in what state is this art. J Thorac Oncol. 2015;10(7):985-9.
13. Ancevski-Hunter K, Socinski MA, Villaruz LC. PD-L1 testing in guiding patient selection for PD-1/PD-L1 inhibitor therapy in lung cancer. Mol diag ther. 2018;22(1):1-10.
14. Tsao MS, Kerr MK, Dacic S, Yatabe Y, Hirsch RF. IASLC atlas of PD-L1 immunohistochemistry testing in lung cancer. 1st ed. North Fort Myers: Editorial RX Press; 2017.
15. Driver BR, Miller RA, Miller T, Deavers M, Gorman B, Mody D, et al. Programmed death ligand-1 (PD-L1) expression in either tumor cells or tumor-infiltrating immune cells correlates with solid and high-grade lung adenocarcinomas. Arch Pathol Lab Med. 2017;141(11):1529-32.
16. Wu S, Shi X, Sun J, Liu Y, Luo Y, Liang Z, et al. The significance of programmed cell death ligand 1 expression in resected lung adenocarcinoma. Oncotarget. 2017;8(10):16421-9.
17. Del C Monroig-Bosque P, Driver B, Morales-Rosado JA, Deavers M, Tacha D, Bernicker E, 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. In press. DOI: 10.5858/arpa.2017-0516-OA.
18. El-Basmy A. Profile of lung cancer in Kuwait. Asian Pac J Cancer Prev. 2013;14(10):6181-4.
19. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010 Sep-Oct;60(5):277-300.
20. Yoshizawa A, Sumiyoshi S, Sonobe M, Kobayashi M, Fujimoto M, Kawakami F, et al. Validation of the IASLC/ATS/ERS lung adenocarcinoma classification for prognosis and association with EGFR and KRAS gene mutations: analysis of 440 Japanese patients. J Thorac Oncol. 2013 Jan;8(1):52-61.
21. Beau-Faller M, Degeorges A, Rolland E, Mounawar M, Antoine M, Poulot V, et al. Cross-validation study for epidermal growth factor receptor and KRAS mutation detection in 74 blinded non-small cell lung carcinoma samples: a total of 5550 exons sequenced by 15 molecular French laboratories (evaluation of the EGFR mutation status for the administration of EGFR-TKIs in non-small cell lung carcinoma [ERMETIC] project--part 1). J Thorac Oncol. 2011 Jun;6(6):1006-15.
22. Russell PA, Barnett SA, Walkiewicz M, Wainer Z, Conron M, Wright GM, et al. Correlation of mutation status and survival with predominant histologic subtype according to the new IASLC/ATS/ERS lung adenocarcinoma classification in stage III (N2) patients. J Thorac Oncol. 2013 Apr;8(4):461-8.
23. Sun PL, Seol H, Lee HJ, Yoo SB, Kim H, Xu X, et al. High incidence of EGFR mutations in  Korean men smokers with no intratumoral heterogeneity of lung adenocarcinomas: correlation with histologic subtypes, EGFR/TTF-1 expressions, and clinical features.  J Thorac Oncol. 2012 Feb;7(2):323-30.
24. Zhu P, Pan Q, Wang M. Efficacy of bronchoscopic biopsy for the detection of epidermal growth factor receptor mutations and anaplastic lymphoma kinase gene rearrangement in lung adenocarcinoma. Thorac Cancer.  2015 Nov;6(6):709-14.
25. Miyazawa, T., Marushima, H., Saji, H., Kojima, K., Hoshikawa, M., Takagi, M., & Nakamura, H. (2019). PD-L1 Expression in Non-Small-Cell Lung Cancer Including Various Adenocarcinoma Subtypes. Annals of thoracic and cardiovascular surgery : official journal of the Association of Thoracic and Cardiovascular Surgeons of Asia, 25(1), 1–9. https://doi.org/10.5761/atcs.oa.18-00163
26. Lin SY, Yang CY, Liao BC, Ho CC, Liao WY, Chen KY, Tsai TH, Hsu CL, Hsu WH, Su KY, Chang YL, Lee JH, Lin CC, Shih JY, Yang JC, Yu CJ. Tumor PD-L1 Expression and Clinical Outcomes in Advanced-stage Non-Small Cell Lung Cancer Patients Treated with Nivolumab or Pembrolizumab: Real-World Data in Taiwan. J Cancer. 2018 Apr 19;9(10):1813-1820. doi: 10.7150/jca.24985. PMID: 29805708; PMCID: PMC5968770.
27. Trevis W, Brambilla E, Burke A, Marx A, Nicholson A. WHO Classification of tumours of the lung, pleura, thumus and heart. Lyon: IARC; 2015.
28. Howlader N, Noone AM, Krapcho M, Garshell J, Miller D, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA, editors. SEER Cancer Statistics Review, 1975-2012. Bethesda: National Cancer Institute. Available from: http://seer.cancer.gov/csr/1975_2012/ , based on November 2014 SEER data submission, posted to the SEER web site, April 2015.
29. Yu H, Boyle AT, Zhou C, Rimm LD, Hirsch RF. PD-L1 expression in lung cancer. J Thorac Oncol. 2017; 12(1): 157–9.
30. Kato Y, Kashima J, Watanabe K, Yomota M, Zenke Y, Okuma Y, et al. Association between clinicopathological features and programmed death ligand expression in non-small cell lung cancer. Anticancer Res. 2018;38(2):1077-83.
31. Heymann JJ, Bulman WA, Swinarski D, Pagan CA, Crapanzano JP, Haghighi M, et al. PD-L1 expression in non-small cell lung carcinoma: comparison among cytology, small biopsy, and surgical resection specimens. Cancer Cytopathol. 2017;125(12):896-907.
32. Thunnissen E, Allen TC, Adam J, Aisner LD, Beasley BM, Borczuk CA, et al. Immunohistochemistry of pulmonary biomarkers: a perspective from members of the Pulmonary Pathology Society. Arch Pathol Lab Med. 2018;142:408-19.
33. Takeda M, Kasai T, Naito M, Tamiya A, Taniguchi Y, Saijo N, Naoki Y, Okishio K, Shimizu S, Kojima K, Nagoya A, Sakamoto T, Utsumi T, Yoon HE, Matsumura A, Atagi S. Programmed Death-ligand 1 Expression With Clone 22C3 in Non-small Cell Lung Cancer: A Single Institution Experience. Clin Med Insights Oncol. 2019 Jan 9;13:1179554918821314. doi: 10.1177/1179554918821314. PMID: 30670923; PMCID: PMC6329032
    

PDF01-MD-Vol 13 No 2 Jun 2021_Tegeltija et al.