A Novel Approach to Detect Programed Death Ligand 1 (PD-L1) Status and Multiple Tumor Mutations Using a Single NonSmall-Cell Lung Cancer (NSCLC) Bronchoscopy Specimen

Vannitamby, A, Hendry, S, Makadia, T, Danks, J, Slavin, J, Irving, L, Steinfort, D and Bozinovski, S 2019, 'A Novel Approach to Detect Programed Death Ligand 1 (PD-L1) Status and Multiple Tumor Mutations Using a Single NonSmall-Cell Lung Cancer (NSCLC) Bronchoscopy Specimen', Journal of Molecular Diagnostics, vol. 21, no. 2, pp. 186-197.


Document type: Journal Article
Collection: Journal Articles

Title A Novel Approach to Detect Programed Death Ligand 1 (PD-L1) Status and Multiple Tumor Mutations Using a Single NonSmall-Cell Lung Cancer (NSCLC) Bronchoscopy Specimen
Author(s) Vannitamby, A
Hendry, S
Makadia, T
Danks, J
Slavin, J
Irving, L
Steinfort, D
Bozinovski, S
Year 2019
Journal name Journal of Molecular Diagnostics
Volume number 21
Issue number 2
Start page 186
End page 197
Total pages 12
Publisher Elsevier
Abstract Multiple biomarkers are under evaluation to guide the use of immune checkpoint inhibitors in nonsmall-cell lung cancer (NSCLC), including programed death ligand 1 (PD-L1) tumor cell staining. We have developed a new approach that accurately quantifies PD-L1 status and identifies multiple mutations by using a single bronchoscopy specimen. A novel molecular marker was identified to detect the presence of malignant cells in radial endobronchial ultrasound bronchial brushings from NSCLC (n = 15) and benign (n = 13) nodules by quantitative real-time RT-PCR (RT-qPCR). The MMP9:TIMP3 transcript ratio was significantly increased in NSCLC and using receiver operating characteristic curve analysis accurately discriminated malignant and benign bronchoscopy specimens (area under the curve = 0.98; 95% CI, 0.931; P < 0.0001). Utilizing the same specimens, PD-L1 expression and multiple oncogenic mutations were detected by RT-qPCR and next-generation sequencing. A second archive of snap-frozen squamous cell carcinoma (n = 40) and control (n = 20) biopsies with matching formalin-fixed, paraffin-embedded slides were used to compare PD-L1 status by immunohistochemistry and RT-qPCR. The biopsy cohort confirmed that the MMP-9:TIMP3 ratio was predictive of malignancy and demonstrated that PD-L1 transcript expression was concordant with PD-L1 tumor cell membrane staining in NSCLC (Spearman r = 0.636, P < 0.0001). This rapid molecular approach can detect malignant cells and using the same single bronchoscopy specimen can generate high-quality unfixed nucleic acid that accurately quantify PD-L1 status and identify multiple oncogenic mutations.
Subject Respiratory Diseases
Keyword(s) Brush-Tip Washings
Endobronchial Ultrasound
Diagnostic Utility
Tissue
Feasibility
Inhibition
Invasion
DOI - identifier 10.1016/j.jmoldx.2018.10.001
Copyright notice Copyright © 2019 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0).
ISSN 1525-1578
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 1 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 0 times in Scopus Article
Altmetric details:
Access Statistics: 1 Abstract Views  -  Detailed Statistics
Created: Tue, 06 Aug 2019, 08:28:00 EST by Catalyst Administrator
© 2014 RMIT Research Repository • Powered by Fez SoftwareContact us