Routine Clinically Detected Increased ROS1 Transcripts Are Related With ROS1 Expression by Immunohistochemistry and Associated With EGFR Mutations in Lung Adenocarcinoma

Karl Grenier; Jean-Baptiste Rivière; Bouchra Ouled Amar Bencheikh; Andrea Liliam Gomez Corredor; Benjamin Christopher Shieh; Hangjun Wang; Pierre Olivier Fiset; Sophie Camilleri-Broët

doi:10.1016/j.jtocrr.2023.100530

Routine Clinically Detected Increased ROS1 Transcripts Are Related With ROS1 Expression by Immunohistochemistry and Associated With EGFR Mutations in Lung Adenocarcinoma

JTO Clin Res Rep. 2023 May 24;4(7):100530. doi: 10.1016/j.jtocrr.2023.100530. eCollection 2023 Jul.

Authors

Karl Grenier^{1

2}, Jean-Baptiste Rivière^{2

3}, Bouchra Ouled Amar Bencheikh^{2

3}, Andrea Liliam Gomez Corredor^{1

2

3}, Benjamin Christopher Shieh⁴, Hangjun Wang^{1

2}, Pierre Olivier Fiset^{1

2}, Sophie Camilleri-Broët^{1

2}

Affiliations

¹ Department of Pathology, McGill University Health Center, Montreal, Quebec, Canada.
² Department of Laboratory Medicine, Montreal, Quebec, Canada.
³ Division of Molecular Genetics, McGill University Health Center, Montreal, Quebec, Canada.
⁴ Respiratory Division, Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada.

Abstract

Introduction: Translocations of the ROS1 gene were found to drive tumorigenesis in 1% to 2% of lung adenocarcinoma. In clinical practice, ROS1 rearrangements are often screened by immunohistochemistry (IHC) before confirmation with either fluorescence in situ hybridization or molecular techniques. This screening test leads to a non-negligible number of cases that have equivocal or positive ROS1 IHC, without ROS1 translocation.

Methods: In this study, we have analyzed retrospectively 1021 cases of nonsquamous NSCLC having both ROS1 IHC and molecular analysis using next-generation sequencing.

Results: ROS1 IHC was negative in 938 cases (91.9%), equivocal in 65 cases (6.4%), and positive in 18 cases (1.7%). Among these 83 equivocal or positive cases, only two were ROS1 rearranged, leading to a low predictive positive value of the IHC test (2%). ROS1-positive IHC was correlated with an increased mRNA ROS1 transcripts. Moreover, we have found a mean statistically significant relationship between ROS1 expression and EGFR gene mutations, suggesting a crosstalk mechanism between these oncogenic driver molecules.

Conclusion: This study demonstrates that ROS1 IHC represents true ROS1 mRNA expression, and raises the question of a potential benefit of combined targeted therapy in EGFR-mutated NSCLC.

Keywords: Biomarker; EGFR; Immunohistochemistry; Lung adenocarcinoma; NSCLC; ROS1.