title: Immunohistochemical Detection of ROS1 Fusion.
abstract: OBJECTIVE
  Patients whose tumors harbor ROS1 translocation may benefit from targeted therapy. Detection of ROS1 rearrangement can be done by three methods: immunohistochemistry, fluorescence in situ hybridization, and molecular assays. Immunohistochemistry would be a cost-effective means to screen for ROS1 translocation, which is uncommon.
  
  
  METHODS
  ROS1 immunostain was performed on cases with known ROS1 translocation status detected either by fluorescence in situ hybridization or next-generation sequencing.
  
  
  RESULTS
  Fifty-seven cases, 10 lung carcinomas with ROS1 rearrangement and 47 cases without ROS1 rearrangement (25 lung carcinomas, 13 gastrointestinal carcinomas, three brain tumors, and six miscellaneous tumors), were included. ROS1 immunostain exhibited 100% sensitivity and 85% specificity, with staining seen in 10 (100%) of 10 cases with ROS1 rearrangement and in seven (15%) of 47 lung cases without ROS1 rearrangement. Weak or 1+ staining of reactive pneumocytes was seen in eight (14%) of 57 cases, and strong staining of osteoclast giant cells was seen in one case.
  
  
  CONCLUSIONS
  Since ROS1 rearrangement is an infrequent event, immunohistochemistry is a cost-effective screening method. Confirmation of all positive and equivocal/weak staining with molecular assays would exclude the false-positive cases.
authors.affiliation: From the Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Su
authors.affiliation: From the Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston.
authors.forename: Theodore
authors.initials: T
authors.lastname: Goncalves
authors.affiliation: From the Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston.
authors.forename: Dora
authors.initials: D
authors.lastname: Dias-Santagata
authors.affiliation: From the Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston.
authors.forename: Mai P
authors.initials: MP
authors.lastname: Hoang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D000077192:Adenocarcinoma of Lung; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000032:analysis*; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*
chemical_list: D015514:Oncogene Proteins, Fusion; D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; C062333:ROS1 protein, human
keywords: Colorectal carcinoma; Immunohistochemistry; Lung carcinoma; ROS1; Translocation