Comparison of Next-Generation Sequencing and Immunohistochemistry Analysis for Targeted Therapy-Related Genomic Status in Lung Cancer Patients.

BACKGROUND:Some drugs that target molecular pathways are available for the targeted treatment of lung cancer. Multiple tests are needed to detect the status of the known molecular targets to determine whether the patients can respond to the drugs. An integrated platform for various gene alteration detection including both mutations and rearrangements is necessary for patients, especially those without enough tissue.METHODS:In our study, detections of EGFR mutations, ALK rearrangement, ROS1 rearrangement, and alterations of other nine important lung cancer-related genes were integrated into a single next-generation sequencing (NGS) platform. The NGS analysis was performed in 107 cases of non-small cell lung cancer (NSCLC). Meanwhile, hot spots such as EGFR L858R, EGFR E746-A750Del mutations and gene rearrangement of ALK and ROS1 were detected by immunohistochemical (IHC) staining.RESULTS:NGS could explore various gene mutations and gene rearrangements with a reduced experiment time and lower amounts of tumor tissues than multiple IHC staining experiments. NGS results were more informative and reliable than IHC staining for EGFR gene alterations, especially for the exon 19 region. NGS could also increase the positive rate of ALK rearrangement and decrease the false positive results of ROS1 rearrangements detected by IHC staining.CONCLUSIONS:NGS is effective for confirmation the status of various important lung cancer-related gene alterations. Furthermore, NGS is necessary for the confirmation of the IHC results of ALK and ROS1 rearrangements.