Detection of ROS1 gene rearrangement in lung adenocarcinoma: comparison of IHC, FISH and real-time RT-PCR.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science

Gene Rearrangement*; Adenocarcinoma/*genetics ; Adenocarcinoma/*metabolism ; Immunohistochemistry/*methods ; In Situ Hybridization, Fluorescence/*methods ; Lung Neoplasms/*genetics ; Lung Neoplasms/*metabolism ; Real-Time Polymerase Chain Reaction/*methods; Adenocarcinoma of Lung ; Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Oncogene Proteins, Fusion/genetics ; Oncogene Proteins, Fusion/metabolism ; Protein-Tyrosine Kinases/genetics ; Protein-Tyrosine Kinases/metabolism ; Proto-Oncogene Proteins/genetics ; Proto-Oncogene Proteins/metabolism ; Sensitivity and Specificity

Aims: To compare fluorescence in situ hybridization (FISH), immunohistochemistry (IHC) and quantitative real-time reverse transcription-PCR (qRT-PCR) assays for detection of ROS1 fusion in a large number of ROS1-positive lung adenocatcinoma (ADC) patients.
Methods: Using IHC analysis, sixty lung ADCs including 16 cases with ROS1 protein expression and 44 cases without ROS1 expression were selected for this study. The ROS1 fusion status was examined by FISH and qRT-PCR assay.
Results: Among 60 cases, 16 (26.7%), 13 (21.7%) and 20 (33.3%) cases were ROS1 positive revealed by IHC, FISH and qRT-PCR, respectively. Using FISH as a standard method for ROS1 fusion detection, the sensitivity and specificity of IHC were 100% and 93.6%, respectively. Three IHC-positive cases, which showed FISH negative, were demonstrated with ROS1 fusion by qRT-PCR analysis. The sensitivity and specificity of qRT-PCR for detection for ROS1 fusion were 100% and 85.1%, respectively. The total concordance rate between IHC and qRT-PCR were 93.3%.
Conclusion: IHC is a reliable and rapid screening tool in routine pathologic laboratories for the identification of suitable candidates for ROS1-targeted therapy. Some ROS1 IHC-positive but FISH-negative cases did harbor the translocation events and may benefit from crizotinib.

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0 (Oncogene Proteins, Fusion)
0 (Proto-Oncogene Proteins)
EC 2.7.10.1 (Protein-Tyrosine Kinases)
EC 2.7.10.1 (ROS1 protein, human)

Date Created: 20150306 Date Completed: 20160115 Latest Revision: 20220408

20240829

PMC4351102

10.1371/journal.pone.0120422

25742289