Detection of ROS1 rearrangement in non-small cell lung cancer: current and future perspectives
Giulio Rossi1, Genny Jocollé2, Antonia Conti3
1Pathology Unit.
Abstract:
ROS1 rearrangement characterizes a small subset (1%-2%) of non-small cell lung cancer and is associated with slight/never smoking patients and adenocarcinoma histology. Identification of ROS1 rearrangement is mandatory to permit targeted therapy with specific inhibitors, demonstrating a significantly better survival when compared with conventional chemotherapy. Detection of ROS1 rearrangement is based on in situ (immunohistochemistry, fluorescence in situ hybridization) and extractive non-in situ assays. While fluorescence in situ hybridization still represents the gold standard in clinical trials, this technique may fail to recognize rearrangements of ROS1 with some gene fusion partner. On the other hand, immunohistochemistry is the most cost-effective screening technique, but it seems to be characterized by low specificity. Extractive molecular assays are expensive and laborious methods, but they specifically recognize almost all ROS1 fusions using a limited amount of mRNA even from formalin-fixed, paraffin-embedded tumor tissues. This review is a discussion on the present and futuristic diagnostic scenario of ROS1 identification in lung cancer.
Insights
Identifying ROS1 rearrangements in non-small cell lung cancer is crucial for targeted therapy. This review discusses current and future diagnostic methods for ROS1 gene fusions, essential for improving patient survival.
Area of Science:
- Oncology
- Molecular Diagnostics
- Genetics
Background:
- ROS1 rearrangements occur in 1%-2% of non-small cell lung cancer (NSCLC).
- These rearrangements are linked to specific patient demographics (slight/never smokers) and adenocarcinoma histology.
- Targeted therapy with ROS1 inhibitors offers improved survival over conventional chemotherapy.
Purpose of the Study:
- To review the current diagnostic landscape for ROS1 rearrangements in NSCLC.
- To discuss the advantages and limitations of various detection methods.
- To explore future directions in ROS1 diagnostic strategies.
Main Methods:
- Review of existing literature on ROS1 rearrangement detection in NSCLC.
- Comparison of in situ hybridization (FISH), immunohistochemistry (IHC), and molecular assays.
- Analysis of diagnostic accuracy, cost-effectiveness, and clinical utility.
Main Results:
- FISH is the clinical trial gold standard but may miss certain ROS1 fusions.
- IHC is cost-effective for screening but has lower specificity.
- Extractive molecular assays are accurate for nearly all ROS1 fusions but are costly and labor-intensive.
Conclusions:
- Accurate ROS1 rearrangement detection is vital for NSCLC targeted therapy selection.
- Each diagnostic method presents a unique balance of sensitivity, specificity, cost, and practicality.
- Future strategies should aim to optimize ROS1 testing for improved patient outcomes.
