PD‐L1 expression in ROS1‐rearranged non‐small cell lung cancer: A study using simultaneous genotypic screening of EGFR, ALK, and ROS1

• Published in: Thoracic cancer Vol. 10; no. 1; pp. 103 - 110
• Main Authors: Lee, Jongmin, Park, Chan Kwon, Yoon, Hyoung‐Kyu, Sa, Young Jo, Woo, In Sook, Kim, Hyo Rim, Kim, Sue Youn, Kim, Tae‐Jung
• Format: Journal Article
• Language: English
• Published: Melbourne John Wiley & Sons Australia, Ltd 01-01-2019; John Wiley & Sons, Inc; Wiley
• Subjects: Adult; Aged; Anaplastic Lymphoma Kinase - genetics; B7-H1 Antigen - genetics; Biomarker; Biomarkers; Biomarkers, Tumor - genetics; Carcinoma, Non-Small-Cell Lung - diagnosis; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; Cloning; Deoxyribonucleic acid; DNA; Early Detection of Cancer; epidermal growth factor receptor; ErbB Receptors - genetics; FDA approval; Female; Gene Expression Regulation, Neoplastic; Gene Rearrangement - genetics; Genotype; human ROS1 protein; Humans; In Situ Hybridization, Fluorescence; Kinases; Lung cancer; Male; Middle Aged; Mutation; non‐small cell lung carcinoma; Original; Patients; programmed death 1 ligand 1; Protein-Tyrosine Kinases - genetics; Proto-Oncogene Proteins - genetics; Smoking; Studies; United States > US; South Korea; human ROS1 protein; programmed death 1 ligand 1; Biomarker; non-small cell lung carcinoma; epidermal growth factor receptor
• ISSN: 1759-7706; 1759-7714
• DOI: 10.1111/1759-7714.12917

Background
The aim of the current study was to investigate the prevalence and clinicopathologic characteristics of ROS1‐rearranged non‐small cell lung cancer (NSCLC) in routine genotypic screening in conjunction with the study of PD‐L1 expression, a biomarker for first‐line treatment decisions.
Methods
Reflex simultaneous genotypic screening for EGFR by peptide nucleic acid clamping, and ALK and ROS1 by fluorescence in situ hybridization (FISH) was performed on consecutive NSCLC cases at the time of initial pathologic diagnosis. We evaluated genetic aberrations, clinicopathologic characteristics, and PD‐L1 tumor proportion score (TPS) using a PD‐L1 22C3 assay kit.
Results
In 407 consecutive NSCLC patients, simultaneous genotyping identified 14 (3.4%) ROS1 and 19 (4.7%) ALK rearrangements, as well as 106 (26%) EGFR mutations. These mutations were mutually exclusive and were found in patients with similar clinical features, including younger age, a prevalence in women, adenocarcinoma, and advanced stage. The PD‐L1 assay was performed on 130 consecutive NSCLC samples. High PD‐L1 expression (TPS ≥ 50%) was observed in 29 (22.3%) tumors. PD‐L1 expression (TPS ≥ 1%) was significantly associated with wild type EGFR, while ROS1 rearrangement was associated with high PD‐L1 expression. Of the 14 cases with ROS1 rearrangement, 12 (85.7%) showed PD‐L1 expression and 5 (35.7%) showed high PD‐L1 expression.
Conclusion
In the largest consecutive routine Asian NSCLC cohort analyzed to date, we found that high PD‐L1 expression frequently overlapped with ROS1 rearrangement, while it negatively correlated with EGFR mutations.