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(Abstract)

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This study aimed to optimize the molecular course of action for non-small cell lung cancer (NSCLC) patients with a positive ROS1 immunohistochemistry (IHC) test. The researchers analyzed a retrospective cohort of NSCLC cases with positive ROS1 IHC and performed molecular testing to detect ROS1 fusions and targetable mutations. The ROS1 IHC tumors were graded using the H-score and analyzed using next-generation sequencing (NGS).<br /><br />Out of 1040 NSCLC cases, 36 (3.4%) had positive ROS1 IHC with H-scores ranging from 10 to 270. The researchers used ROC curve modeling to predict ROS1 fusions and targetable mutations based on the H-score. They found that an H-score threshold of 150 had high sensitivity (100%) and specificity (82.8%) for predicting ROS1 fusions or EGFR activating mutations. Among the tumors with an H-score above 150, a novel ROS1 TMEM87A fusion was discovered. The remaining tumors with H-scores below 150 did not have ROS1 fusions but 16 of them (83%) had targetable mutations.<br /><br />RNA sequencing in ROS1 IHC samples showed ROS1 RNA expression even in ROS1 fusion-negative tumors, suggesting a higher ROS1 RNA transcription in these cases. The study supports routine quantitative staining assessment using the H-score in ROS1 IHC tumors and proposes an algorithm for molecular testing based on specific H-score thresholds. The findings also raise questions about the role of ROS1 co-expression in these tumors.<br /><br />In conclusion, this study highlights the importance of the H-score in predicting ROS1 fusions and targetable mutations in NSCLC patients with positive ROS1 IHC. It emphasizes the need for standardized molecular testing algorithms based on specific H-score thresholds. The findings also suggest a potential role of ROS1 RNA expression in ROS1 fusion-negative tumors.

Asset Subtitle

Ghassen Soussi

Meta Tag

Speaker Ghassen Soussi

Topic Pathology & Biomarkers: Genetic Biomarkers

Keywords

non-small cell lung cancer

NSCLC

ROS1 immunohistochemistry

molecular testing

ROS1 fusions

targetable mutations

H-score

next-generation sequencing

RNA sequencing

molecular testing algorithms