Study of Programmed Death Ligand 1 and EGFR/HER2 Expression in Non-Small-Cell Lung Carcinoma With a Clinicopathological Spectrum

Overview

Journal Cureus

Specialty Biomedical Engineering

Date 2021 Aug 9

PMID 34367799

Authors

Devina Laishram

Vandana Raphael

Evarisalin Marbaniang

Caleb Harris

Vikas Jagtap

Baphiralyne Wankhar

Affiliations

Soon will be listed here.

Abstract

Non-small-cell lung carcinoma (NSCLC) is a disease characterized by the upregulation of programmed death ligand 1 (PD-L1) along with alterations in epidermal growth factor receptor (EGFR) and HER2-neu (HER2) amplification in addition to EGFR mutation. In the present study, the expression of PD-L1 and EGFR and HER2-neu in NSCLC was studied and their expression in relation to various clinicopathological parameters was analysed. We studied 49 core biopsy specimens of NSCLC for PD-L1, EGFR and HER2-neu expressions using immunohistochemistry. Scoring was based on the intensity and percentage of tumour cells expressing the immunomarkers. PD-L1, EGFR and HER2-neu expression was seen in 20.4%, 32.7% and 14.2% of NSCLC, respectively. The analysis showed no significant difference in PD-L1 expression in relation to any clinicopathological parameters. Low or negative EGFR expression was significantly associated with positive lymph node status (P=0.04). HER2-neu expression showed a significant difference in relation to tumour histology (adenocarcinoma; P=0.01). Also, there was no difference noted with PD-L1 expression in relation to EGFR and HER2-neu expression. As our study has a small number of cases, the validation of the predictive and prognostic value of these markers in lung cancer patients requires further studies.

References

Kintsler S, Cassataro M, Drosch M, Holenya P, Knuechel R, Braunschweig T . Expression of programmed death ligand (PD-L1) in different tumors. Comparison of several current available antibody clones and antibody profiling. Ann Diagn Pathol. 2019; 41:24-37. DOI: 10.1016/j.anndiagpath.2019.05.005. View

Takenaka M, Hanagiri T, Shinohara S, Kuwata T, Chikaishi Y, Oka S . The prognostic significance of HER2 overexpression in non-small cell lung cancer. Anticancer Res. 2011; 31(12):4631-6. View

Aviles-Salas A, Muniz-Hernandez S, Maldonado-Martinez H, Chanona-Vilchis J, Ramirez-Tirado L, Hernandez-Pedro N . Reproducibility of the EGFR immunohistochemistry scores for tumor samples from patients with advanced non-small cell lung cancer. Oncol Lett. 2017; 13(2):912-920. PMC: 5351342. DOI: 10.3892/ol.2016.5512. View

da Cunha Santos G, Shepherd F, Tsao M . EGFR mutations and lung cancer. Annu Rev Pathol. 2010; 6:49-69. DOI: 10.1146/annurev-pathol-011110-130206. View

Woodburn J . The epidermal growth factor receptor and its inhibition in cancer therapy. Pharmacol Ther. 1999; 82(2-3):241-50. DOI: 10.1016/s0163-7258(98)00045-x. View

Auliac J, Do P, Bayle S, Doubre H, Vinas F, Letreut J . Non-Small Cell Lung Cancer Patients Harboring HER2 Mutations: Clinical Characteristics and Management in a Real-Life Setting. Cohort HER2 EXPLORE GFPC 02-14. Adv Ther. 2019; 36(8):2161-2166. PMC: 6822870. DOI: 10.1007/s12325-019-01001-9. View

Schmidt L, Kummel A, Gorlich D, Mohr M, Brockling S, Mikesch J . PD-1 and PD-L1 Expression in NSCLC Indicate a Favorable Prognosis in Defined Subgroups. PLoS One. 2015; 10(8):e0136023. PMC: 4552388. DOI: 10.1371/journal.pone.0136023. View

Goldstraw P, Chansky K, Crowley J, Rami-Porta R, Asamura H, Eberhardt W . The IASLC Lung Cancer Staging Project: Proposals for Revision of the TNM Stage Groupings in the Forthcoming (Eighth) Edition of the TNM Classification for Lung Cancer. J Thorac Oncol. 2016; 11(1):39-51. DOI: 10.1016/j.jtho.2015.09.009. View

Liu L, Shao X, Gao W, Bai J, Wang R, Huang P . The role of human epidermal growth factor receptor 2 as a prognostic factor in lung cancer: a meta-analysis of published data. J Thorac Oncol. 2010; 5(12):1922-32. DOI: 10.1097/jto.0b013e3181f26266. View

10.

Okita R, Maeda A, Shimizu K, Nojima Y, Saisho S, Nakata M . PD-L1 overexpression is partially regulated by EGFR/HER2 signaling and associated with poor prognosis in patients with non-small-cell lung cancer. Cancer Immunol Immunother. 2017; 66(7):865-876. PMC: 11028751. DOI: 10.1007/s00262-017-1986-y. View

11.

Bethune G, Bethune D, Ridgway N, Xu Z . Epidermal growth factor receptor (EGFR) in lung cancer: an overview and update. J Thorac Dis. 2012; 2(1):48-51. PMC: 3256436. View

12.

Pellegrini C, Falleni M, Marchetti A, Cassani B, Miozzo M, Buttitta F . HER-2/Neu alterations in non-small cell lung cancer: a comprehensive evaluation by real time reverse transcription-PCR, fluorescence in situ hybridization, and immunohistochemistry. Clin Cancer Res. 2003; 9(10 Pt 1):3645-52. View

13.

Landi L, Cappuzzo F . HER2 and lung cancer. Expert Rev Anticancer Ther. 2013; 13(10):1219-28. DOI: 10.1586/14737140.2013.846830. View

14.

Zhang M, Li G, Wang Y, Zhao S, Haihong P, Zhao H . PD-L1 expression in lung cancer and its correlation with driver mutations: a meta-analysis. Sci Rep. 2017; 7(1):10255. PMC: 5578960. DOI: 10.1038/s41598-017-10925-7. View

15.

Bylicki O, Paleiron N, Margery J, Guisier F, Vergnenegre A, Robinet G . Targeting the PD-1/PD-L1 Immune Checkpoint in EGFR-Mutated or ALK-Translocated Non-Small-Cell Lung Cancer. Target Oncol. 2017; 12(5):563-569. DOI: 10.1007/s11523-017-0510-9. View

16.

Li A, Chitale D, Riely G, Pao W, Miller V, Zakowski M . EGFR mutations in lung adenocarcinomas: clinical testing experience and relationship to EGFR gene copy number and immunohistochemical expression. J Mol Diagn. 2008; 10(3):242-8. PMC: 2329789. DOI: 10.2353/jmoldx.2008.070178. View

17.

Yu H, Boyle T, Zhou C, Rimm D, Hirsch F . PD-L1 Expression in Lung Cancer. J Thorac Oncol. 2016; 11(7):964-75. PMC: 5353357. DOI: 10.1016/j.jtho.2016.04.014. View

18.

Pugh T, Bebb G, Barclay L, Sutcliffe M, Fee J, Salski C . Correlations of EGFR mutations and increases in EGFR and HER2 copy number to gefitinib response in a retrospective analysis of lung cancer patients. BMC Cancer. 2007; 7:128. PMC: 1952070. DOI: 10.1186/1471-2407-7-128. View

19.

Chen N, Fang W, Zhan J, Hong S, Tang Y, Kang S . Upregulation of PD-L1 by EGFR Activation Mediates the Immune Escape in EGFR-Driven NSCLC: Implication for Optional Immune Targeted Therapy for NSCLC Patients with EGFR Mutation. J Thorac Oncol. 2015; 10(6):910-23. DOI: 10.1097/JTO.0000000000000500. View

20.

Ohsaki Y, Tanno S, Fujita Y, Toyoshima E, Fujiuchi S, Nishigaki Y . Epidermal growth factor receptor expression correlates with poor prognosis in non-small cell lung cancer patients with p53 overexpression. Oncol Rep. 2000; 7(3):603-7. DOI: 10.3892/or.7.3.603. View