Immunohistochemical Detection of ROS1 Fusion
Yuhua Su1, Theodore Goncalves1, Dora Dias-Santagata1
1From the Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston.
Objectives:
Patients whose tumors harbor ROS1 translocation may benefit from targeted therapy. Detection of ROS1 rearrangement can be done by three methods: immunohistochemistry, fluorescence in situ hybridization, and molecular assays. Immunohistochemistry would be a cost-effective means to screen for ROS1 translocation, which is uncommon.
Methods:
ROS1 immunostain was performed on cases with known ROS1 translocation status detected either by fluorescence in situ hybridization or next-generation sequencing.
Results:
Fifty-seven cases, 10 lung carcinomas with ROS1 rearrangement and 47 cases without ROS1 rearrangement (25 lung carcinomas, 13 gastrointestinal carcinomas, three brain tumors, and six miscellaneous tumors), were included. ROS1 immunostain exhibited 100% sensitivity and 85% specificity, with staining seen in 10 (100%) of 10 cases with ROS1 rearrangement and in seven (15%) of 47 lung cases without ROS1 rearrangement. Weak or 1+ staining of reactive pneumocytes was seen in eight (14%) of 57 cases, and strong staining of osteoclast giant cells was seen in one case.
Conclusions:
Since ROS1 rearrangement is an infrequent event, immunohistochemistry is a cost-effective screening method. Confirmation of all positive and equivocal/weak staining with molecular assays would exclude the false-positive cases.
Insights
Immunohistochemistry is a cost-effective screening tool for detecting ROS1 rearrangements in tumors. Molecular assays are recommended to confirm positive or equivocal staining, ensuring accurate diagnosis for targeted therapy.
Area of Science:
- Oncology
- Molecular Pathology
- Diagnostic Pathology
Background:
- ROS1 rearrangements are biomarkers for targeted therapy in certain cancers.
- Accurate detection of ROS1 rearrangements is crucial for patient treatment.
- Current detection methods include immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and molecular assays.
Purpose of the Study:
- To evaluate the diagnostic performance of ROS1 immunohistochemistry (IHC) as a screening tool.
- To determine the sensitivity and specificity of ROS1 IHC.
- To assess the cost-effectiveness of IHC for identifying ROS1 rearrangements.
Main Methods:
- ROS1 IHC was performed on 57 cases with known ROS1 translocation status.
- ROS1 status was previously confirmed by FISH or next-generation sequencing.
- Cases included lung carcinomas, gastrointestinal carcinomas, brain tumors, and miscellaneous tumors.
Main Results:
- ROS1 IHC demonstrated 100% sensitivity and 85% specificity.
- All 10 cases with ROS1 rearrangement showed positive staining.
- Seven of 47 cases without rearrangement showed non-specific staining.
Conclusions:
- Immunohistochemistry serves as a cost-effective initial screening method for ROS1 rearrangements.
- Molecular assays are essential for confirming positive and equivocal IHC results.
- This approach optimizes the identification of patients eligible for ROS1-targeted therapies.
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