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Published on: September 25, 2018
Detection of ROS1-positive non-small cell lung cancer on cytological specimens using immunocytochemistry
Tatjana Vlajnic1, Spasenija Savic1, Audrey Barascud1
1Institute of Pathology, University Hospital Basel, Basel, Switzerland.
Background:
Rearrangements of the ROS1 oncogene are found in 1% to 2% of non-small cell lung cancers (NSCLC) and are regarded as mutually exclusive oncogenic driver mutations. Since the approval of targeted therapy for ROS1-positive NSCLC, ROS1 testing has become a part of the diagnostic routine. Fluorescence in situ hybridization (FISH), optionally selected for by immunohistochemistry on histological material, is a common practice for the detection of ROS1 rearrangements. However, NSCLC often is diagnosed by cytology alone, requiring predictive marker testing on cytological specimens. In the current study, the authors explored the accuracy of ROS1 immunocytochemistry (ICC) on non-cell block cytological specimens for the detection of ROS1 rearrangements.
Methods:
ICC using the D4D6 antibody on an automated immunostainer was performed prospectively in the routine diagnostic setting on cytological specimens from 295 patients with NSCLC, including adenocarcinoma (241 patients), NSCLC not otherwise specified (50 patients), and other malignancies (4 patients). Any immunostaining was considered positive.
Results:
ICC was positive in all 13 ROS1-rearranged NSCLC cases confirmed by FISH (12 cases) or next-generation sequencing (1 case). Confirmation of 282 ICC-negative cases was available for 208 patients. The sensitivity, specificity, and positive and negative predictive values for ROS1 ICC compared with the final ROS1 status all were 100%.
Conclusions:
ROS1 ICC is an accurate method for the detection of ROS1 rearrangements in NSCLC. Given the high costs and technical challenges of FISH and the rarity of ROS1 rearrangements, ICC is rapid and therefore well suited as a screening method. Cases with equivocal or positive findings on ICC can be confirmed by FISH or molecular tests. Cancer Cytopathol 2018;126:421-9. © 2018 American Cancer Society.
Insights
ROS1 immunocytochemistry (ICC) accurately detects ROS1 rearrangements in non-small cell lung cancer (NSCLC) cytology specimens. This rapid screening method is ideal for identifying patients who may benefit from targeted therapy.
Area of Science:
- Oncology
- Molecular Diagnostics
- Cytopathology
Background:
- ROS1 gene rearrangements occur in 1-2% of non-small cell lung cancers (NSCLC) and are key drivers for targeted therapy.
- ROS1 testing is crucial for NSCLC diagnosis, with Fluorescence In Situ Hybridization (FISH) being a common method.
- Cytological specimens are often used for NSCLC diagnosis, necessitating predictive marker testing on these samples.
Purpose of the Study:
- To evaluate the accuracy of ROS1 immunocytochemistry (ICC) on cytological specimens for detecting ROS1 rearrangements in NSCLC.
- To assess ICC as a potential screening tool for ROS1-positive NSCLC.
Main Methods:
- Prospective study involving 295 NSCLC patients.
- ROS1 ICC performed on non-cell block cytological specimens using the D4D6 antibody on an automated immunostainer.
- Comparison of ICC results with FISH or next-generation sequencing (NGS) for confirmation.
Main Results:
- ICC demonstrated 100% sensitivity, specificity, and predictive values for detecting ROS1 rearrangements.
- All 13 ROS1-rearranged NSCLC cases were correctly identified by ICC.
- 208 out of 282 ICC-negative cases were confirmed, showing high concordance.
Conclusions:
- ROS1 ICC is a highly accurate method for detecting ROS1 rearrangements in NSCLC.
- ICC is a rapid and cost-effective screening tool for ROS1 rearrangements, especially in cytology.
- Positive or equivocal ICC results can be confirmed with FISH or molecular tests.
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