title: ROS1 immunohistochemistry among major genotypes of non-small-cell lung cancer.
abstract: BACKGROUND
  ROS1 gene fusions cause several cancers by constitutively activating the ROS1 tyrosine kinase receptor. ROS1-targeted inhibitor therapy improves survival in the approximately 1% to 2% of patients with lung adenocarcinoma with ROS1 gene fusions. Although fluorescence in situ hybridization (FISH) is the standard diagnostic procedure for detecting ROS1 rearrangements, we studied immunohistochemistry (IHC).
  
  
  METHODS
  ROS1 IHC was performed on a selected cohort of 33 lung adenocarcinoma whole tissue specimens with alterations in the EGFR (n = 5), KRAS (n = 5), ERBB2 (HER2) (n = 3), ROS1 (n = 6), ALK (n = 5), and RET (n = 3) genes and pan-negative (n = 6) detected by reverse transcriptase-polymerase chain reaction (RT-PCR) and FISH.
  
  
  RESULTS
  In the cohort of 33 specimens, both ROS1 gene fusion using RT-PCR and high ROS1 protein expression using IHC were detected in 6 specimens. Of these 6 specimens, 5 were also positive by FISH for ROS1 gene rearrangements. All 27 lung cancer specimens that were negative for ROS1 rearrangements by genetic testing had no to low ROS1 protein expression.
  
  
  CONCLUSIONS
  We have optimized ROS1 IHC and scoring to provide high sensitivity and specificity for detecting ROS1 gene rearrangements in whole tissue. ROS1 IHC could be a practical and cost-effective method to screen for ROS1 gene rearrangements.
authors.affiliation: Department of Medical Oncology and Pathology, University of Colorado, Aurora, CO.
authors.forename: Theresa A
authors.initials: TA
authors.lastname: Boyle
authors.affiliation: Division of Integrated Oncology, Institute of Biomedical Research and Innovation, Kobe, Japan; Department of Pathology and Molecular Diagnostics, Aichi Cancer Center, Nagoya, Japan.
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Masago
authors.affiliation: Department of Medical Oncology and Pathology, University of Colorado, Aurora, CO.
authors.forename: Kim E
authors.initials: KE
authors.lastname: Ellison
authors.affiliation: Department of Pathology and Molecular Diagnostics, Aichi Cancer Center, Nagoya, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Yatabe
authors.affiliation: Department of Medical Oncology and Pathology, University of Colorado, Aurora, CO. Electronic address: Fred.Hirsch@ucdenver.edu.
authors.forename: Fred R
authors.initials: FR
authors.lastname: Hirsch
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D000077192:Adenocarcinoma of Lung; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D015321:Gene Rearrangement; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D008175:Lung Neoplasms / Q000235:genetics*; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012680:Sensitivity and Specificity
chemical_list: D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; C062333:ROS1 protein, human
keywords: Adenocarcinoma; Biomarker; Gene rearrangement; NSCLC; ROS1