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Updated: Dec 29, 2025
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Comparison of next-generation sequencing and immunohistochemistry analysis for targeted therapy-related genomic
Lin Nong1, Zhenzhen Zhang2, Yan Xiong1
1Department of Pathology, Peking University First Hospital, Beijing 100034, China.
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.
Insights
Next-generation sequencing (NGS) offers a comprehensive approach for detecting lung cancer gene alterations. This integrated platform is more efficient and reliable than traditional methods, improving patient diagnosis and treatment selection.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Targeted therapies for lung cancer rely on identifying specific molecular alterations.
- Current diagnostic methods often require multiple tests, consuming valuable tissue samples.
- An integrated platform for detecting various gene alterations is crucial for efficient lung cancer patient management.
Purpose of the Study:
- To evaluate the efficacy of a single next-generation sequencing (NGS) platform for detecting multiple lung cancer-related gene alterations.
- To compare the performance of NGS with traditional immunohistochemical (IHC) staining for key molecular targets.
Main Methods:
- An integrated NGS platform was developed to detect mutations and rearrangements in 12 lung cancer-related genes.
- NGS analysis was performed on 107 non-small cell lung cancer (NSCLC) cases.
- Key alterations, including EGFR mutations and ALK/ROS1 rearrangements, were also assessed by IHC staining for comparison.
Main Results:
- NGS demonstrated reduced experiment time and required less tumor tissue compared to multiple IHC staining.
- NGS provided more informative and reliable results for EGFR gene alterations, particularly in exon 19.
- NGS improved the detection rate of ALK rearrangement and reduced false positives for ROS1 rearrangement compared to IHC.
Conclusions:
- NGS is an effective method for confirming the status of various clinically significant lung cancer gene alterations.
- NGS is essential for validating IHC results for ALK and ROS1 rearrangements, enhancing diagnostic accuracy.
