Correlating ROS1 Protein Expression With Fusions, Amplifications, and Mutations.

INTRODUCTION

In this study, we sought to further characterize ROS1 protein expression in solid tumors with the complete spectrum of genomic alterations.

METHODS

ROS1 immunohistochemistry (IHC) was performed using the ROS1 (SP384) class I assay per manufacturer's instructions on a variety of solid tumors (n = 32) with known genomic alterations. Genomic alterations included fusions (n = 17), gene amplifications (n = 10), and short-variant mutations (n = 11).

RESULTS

Of the 32 cases with ROS1 IHC results, 100% (11 of 11) with canonical fusions were positive for ROS1 IHC. Among noncanonical fusions, only two (of five) cases with and fusions were positive for ROS1 IHC whereas - (two) and fusions were negative for ROS1 IHC. One sample with a canonical fusion and co-occurring resistance mutation (6094G>A, p.G2032R) was positive for ROS1 IHC. A total of 10% (one of 10) of amplified tumors were positive for ROS1 IHC. None of the cases (zero of five) with short-variant mutations were positive for ROS1 protein expression.

CONCLUSIONS

These findings suggest that if ROS1 IHC was used as a screening tool for fusion, a subset of fusion-negative tumors will reveal positive IHC staining highlighting the value of reflexing to genomic profiling to confirm the presence of a targetable fusion-driver before the initiation of therapy. In addition, the ability of comprehensive genomic profiling to detect resistance mutations will be important for clinical decision making.