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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.

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