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ROS1 immunohistochemistry among major genotypes of non-small-cell lung cancer
Theresa A Boyle1, Katsuhiro Masago2, Kim E Ellison1
1Department of Medical Oncology and Pathology, University of Colorado, Aurora, CO.
Background:
ROS1 gene fusions cause several cancers by constitutively activating the ROS1 tyrosine kinase receptor. ROS1-targeted inhibitor therapy improves survival in the approximately 1% to 2% of patients with lung adenocarcinoma with ROS1 gene fusions. Although fluorescence in situ hybridization (FISH) is the standard diagnostic procedure for detecting ROS1 rearrangements, we studied immunohistochemistry (IHC).
Materials And Methods:
ROS1 IHC was performed on a selected cohort of 33 lung adenocarcinoma whole tissue specimens with alterations in the EGFR (n = 5), KRAS (n = 5), ERBB2 (HER2) (n = 3), ROS1 (n = 6), ALK (n = 5), and RET (n = 3) genes and pan-negative (n = 6) detected by reverse transcriptase-polymerase chain reaction (RT-PCR) and FISH.
Results:
In the cohort of 33 specimens, both ROS1 gene fusion using RT-PCR and high ROS1 protein expression using IHC were detected in 6 specimens. Of these 6 specimens, 5 were also positive by FISH for ROS1 gene rearrangements. All 27 lung cancer specimens that were negative for ROS1 rearrangements by genetic testing had no to low ROS1 protein expression.
Conclusion:
We have optimized ROS1 IHC and scoring to provide high sensitivity and specificity for detecting ROS1 gene rearrangements in whole tissue. ROS1 IHC could be a practical and cost-effective method to screen for ROS1 gene rearrangements.
Insights
Immunohistochemistry (IHC) shows high accuracy in detecting ROS1 gene rearrangements in lung adenocarcinoma. This optimized ROS1 IHC method offers a practical and cost-effective screening tool for identifying patients who may benefit from targeted therapies.
Area of Science:
- Oncology
- Molecular Diagnostics
- Cancer Biomarkers
Background:
- ROS1 gene fusions drive cancer by activating the ROS1 tyrosine kinase receptor.
- Targeted therapy for ROS1-positive lung adenocarcinoma improves patient survival.
- Fluorescence in situ hybridization (FISH) is the current standard for detecting ROS1 rearrangements.
Purpose of the Study:
- To evaluate the utility of immunohistochemistry (IHC) as a diagnostic method for detecting ROS1 rearrangements.
- To optimize ROS1 IHC and scoring for high sensitivity and specificity.
Main Methods:
- ROS1 IHC was performed on 33 lung adenocarcinoma tissue specimens.
- Specimens had known alterations in EGFR, KRAS, ERBB2, ROS1, ALK, or RET genes, confirmed by RT-PCR and FISH.
- ROS1 IHC results were correlated with genetic testing (RT-PCR and FISH).
Main Results:
- High ROS1 protein expression by IHC correlated with ROS1 gene fusion detected by RT-PCR in 6 specimens.
- 5 of these 6 specimens were FISH-positive for ROS1 rearrangements.
- All 27 specimens negative for ROS1 rearrangements by genetic testing showed no to low ROS1 protein expression by IHC.
Conclusions:
- Optimized ROS1 IHC provides high sensitivity and specificity for detecting ROS1 gene rearrangements in whole tissue specimens.
- ROS1 IHC is a practical and cost-effective screening method for identifying ROS1 rearrangements.
- This IHC approach can help identify lung adenocarcinoma patients eligible for ROS1-targeted therapies.
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