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

Introduction: Translocations of the gene were found to drive tumorigenesis in 1% to 2% of lung adenocarcinoma In clinical practice, 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 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 expression and 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 -mutated NSCLC.