2023 World Conference on Lung Cancer (Posters)-EP06.03. Predicting ROS1 Fusions and Targetable Mutations in Non-small Cell Lung Cancer through H-score Pathological Analysis

EP06.03. Predicting ROS1 Fusions and Targetable Mutations in Non-small Cell Lung Cancer through H-score Pathological Analysis - PDF(Slides)

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A retrospective study was conducted to optimize the molecular testing approach for non-small cell lung cancer (NSCLC) patients with a positive ROS1 immunohistochemistry (IHC) result. The study aimed to determine the appropriate course of action based on the ROS1 IHC H-score. The study found that an H-score threshold of 150 was highly predictive of ROS1 fusions, with a sensitivity of 100% and specificity of 82.8%. Tumors with an H-score above 150 carried either a ROS1 fusion or an EGFR activating mutation. Additionally, a novel ROS1 TMEM87A fusion was discovered in these tumors. Tumors with an H-score below 150 did not harbor any ROS1 fusions but 83% of them carried a targetable mutation. The study suggests that in high H-score carcinomas, first-line molecular testing should include DNA and RNA explorations, as all ROS1 fusions and EGFR mutations were found in this group. In cases of low H-score, DNA analysis should be prioritized, with RNA analysis as a second-line option if needed. The study also highlights that ROS1 IHC expression is more closely associated with higher ROS1 RNA transcription rather than a lack of specificity of ROS1 antibodies. The findings of this study support the use of the H-score for quantitative staining assessment in ROS1 IHC tumors and provide an algorithm for molecular testing based on specific thresholds.

Asset Subtitle

Ghassen Soussi

Meta Tag

Speaker Ghassen Soussi

Topic Pathology & Biomarkers: Genetic Biomarkers

Keywords

retrospective study

molecular testing

non-small cell lung cancer

NSCLC

ROS1 immunohistochemistry

ROS1 IHC H-score

ROS1 fusions

EGFR activating mutation

ROS1 TMEM87A fusion

targetable mutation