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Abstract

Citation: Clin Oncol. 2023;8(1):2005.DOI: 10.25107/2474-1663-v8-id2005

A Comprehensive Study of ROS1 Fusion in Patients with Non-Small-Cell Lung Cancer Using Novel ROS1 Immunohistochemistry Clone (SP384)

Wang Y, Wang Y, Jin Y, Cai X, Shen X, Zhou X and Li Y

Department of Pathology, Fudan University Shanghai Cancer Center, China
Department of Oncology, Shanghai Medical College, Fudan University, China

*Correspondance to: Yuan LI 

 PDF  Full Text Research Article | Open Access

Abstract:

Background: The ROS1 rearrangement is an important oncogenic target in lung cancer patients. Immunohistochemistry (IHC) is a commonly used method to identify potential ROS1 rearrangement in routine clinical practice. In this study, we evaluated a novel ROS1 immunohistochemistry clone (SP384) and investigated the correlation between different ROS1 fusion variants and IHC staining features. Methods: A total of 1380 lung cancers were screened by Next-Generation Sequencing (NGS) or Fluorescence in situ Hybridization (FISH) analysis for ROS1 rearrangement prediction 37 ROS1 NGS/FISH-positive and 173 ROS1 NGS/FISH-negative NSCLC cases were selected for review in this study. All specimens were screened with a novel anti-ROS1 IHC clone (SP384) from Ventana medical systems and a previous anti-ROS1 IHC clone (D4D6) from Cell Signaling Technology. The IHC expression results were evaluated by two pathologists using H-score criteria. Next Generation Sequencing (NGS) is based on a targeted panel of 68 genes. Results: A H-score of 150 or higher could be an optimal cut-off value for this novel anti-ROS1 IHC clone (SP384) to discriminate ROS1 rearranged cases with ROS1 non-rearranged cases with 90% sensitivity and 99% specificity. Compared with anti-ROS1 clone D4D6, SP384 has a higher sensitivity without compromising specificity. Different fusion partners have distinctive IHC staining features and several novel fusion alterations were found. CD74 is the most frequent occurring fusion partner with a strong and diffuse staining pattern. Two ROS1 mutant cases in negative control group were also found presenting moderate, membranous staining with an H-score above 150. Conclusion: The novel anti-ROS1 IHC clone (SP384) could be an outstanding diagnostic alternative in routine clinical practice. Furthermore, this study highlights the importance of IHC in clinical practice that it can be a very supportive tool when used with molecular approaches to interpret fusion alterations like ROS1 and help accurately predict the efficacy of targeted therapy.

Keywords:

ROS1; Immunohistochemistry; Next-generation sequencing; Fusion partners; Functional outcomes; Targeted therapy

Cite the Article:

Wang Y, Wang Y, Jin Y, Cai X, Shen X, Zhou X, et al. A Comprehensive Study of ROS1 Fusion in Patients with Non-Small-Cell Lung Cancer Using Novel ROS1 Immunohistochemistry Clone (SP384). Clin Oncol. 2023;8:2005..

Journal Basic Info

  • Impact Factor: 3.231**
  • H-Index: 11 
  • ISSN: 2474-1663
  • DOI: 10.25107/2474-1663
  • PubMed NLM ID: 101705590

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