Diagnostic Utility of Expression Imbalance in the Idylla GeneFusion Assay for Non-Small-Cell Lung Cancer.

The Idylla GeneFusion Assay detects gene fusions with fusion-specific and expression imbalance methods. The purpose of this study was to evaluate the diagnostic utility of detecting fusions with expression imbalance alone in non-small-cell lung cancer. Results of ALK, ROS1, and RET fusion detection with expression imbalance were compared with results of orthogonal testing. Of 1982 cases reviewed from October 2022 through August 2024, 63 (3.2%) had fusions detected with the expression imbalance method alone, including 47 ALK, 10 ROS1, and 7 RET fusions. One case had ALK and RET fusions. Fluorescence in situ hybridization (FISH) confirmation for 51 cases revealed 8 positive (15.7%), 3 equivocal (5.9%), and 40 negative (78.4%) results. Anaplastic lymphoma kinase (ALK) immunohistochemistry performed for 22 ALK-detected cases revealed 3 positive (13.6%) and 19 negative (86.4%) results that were concordant with ALK FISH results. The positive predictive value of expression imbalance detection alone varied by gene (12.5% for ALK, 16.7% for ROS1, and 33.3% for RET). RNA next-generation sequencing results for seven select cases (three ALK, two ROS1, and two RET) showed six novel fusions (eg, STRN::ALK, SQSTM1::ROS1, and ERC1::RET) and had 100% concordance with FISH results. One case showed an NOL10::ALK out-of-frame fusion with negative ALK immunohistochemistry and equivocal ALK FISH results. Because the expression imbalance method can detect novel fusions, its implementation with confirmation testing is recommended.