PMID- 25467930 OWN - NLM STAT- MEDLINE DCOM- 20151026 LR - 20190221 IS - 1938-0690 (Electronic) IS - 1525-7304 (Print) IS - 1525-7304 (Linking) VI - 16 IP - 2 DP - 2015 Mar TI - ROS1 immunohistochemistry among major genotypes of non-small-cell lung cancer. PG - 106-11 LID - S1525-7304(14)00232-0 [pii] LID - 10.1016/j.cllc.2014.10.003 [doi] AB - 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). MATERIALS AND 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. CONCLUSION: 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. CI - Copyright (c) 2015 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Boyle, Theresa A AU - Boyle TA AD - Department of Medical Oncology and Pathology, University of Colorado, Aurora, CO. FAU - Masago, Katsuhiro AU - Masago K AD - Division of Integrated Oncology, Institute of Biomedical Research and Innovation, Kobe, Japan; Department of Pathology and Molecular Diagnostics, Aichi Cancer Center, Nagoya, Japan. FAU - Ellison, Kim E AU - Ellison KE AD - Department of Medical Oncology and Pathology, University of Colorado, Aurora, CO. FAU - Yatabe, Yasushi AU - Yatabe Y AD - Department of Pathology and Molecular Diagnostics, Aichi Cancer Center, Nagoya, Japan. FAU - Hirsch, Fred R AU - Hirsch FR AD - Department of Medical Oncology and Pathology, University of Colorado, Aurora, CO. Electronic address: Fred.Hirsch@ucdenver.edu. LA - eng GR - P50 CA058187/CA/NCI NIH HHS/United States GR - 2P50CA058187-19A1/CA/NCI NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20141024 PL - United States TA - Clin Lung Cancer JT - Clinical lung cancer JID - 100893225 RN - 0 (Proto-Oncogene Proteins) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) RN - EC 2.7.10.1 (ROS1 protein, human) SB - IM MH - Adenocarcinoma/*genetics MH - Adenocarcinoma of Lung MH - Carcinoma, Non-Small-Cell Lung/*genetics MH - *Gene Rearrangement MH - Genotype MH - Humans MH - Immunohistochemistry/methods MH - In Situ Hybridization, Fluorescence/methods MH - Lung Neoplasms/*genetics MH - Protein-Tyrosine Kinases/*genetics MH - Proto-Oncogene Proteins/*genetics MH - Reverse Transcriptase Polymerase Chain Reaction/methods MH - Sensitivity and Specificity PMC - PMC4770803 MID - NIHMS758611 OTO - NOTNLM OT - Adenocarcinoma OT - Biomarker OT - Gene rearrangement OT - NSCLC OT - ROS1 COIS- All other authors have stated they have no conflicts to disclose. EDAT- 2014/12/04 06:00 MHDA- 2015/10/27 06:00 PMCR- 2016/02/29 CRDT- 2014/12/04 06:00 PHST- 2014/08/20 00:00 [received] PHST- 2014/10/14 00:00 [revised] PHST- 2014/10/21 00:00 [accepted] PHST- 2014/12/04 06:00 [entrez] PHST- 2014/12/04 06:00 [pubmed] PHST- 2015/10/27 06:00 [medline] PHST- 2016/02/29 00:00 [pmc-release] AID - S1525-7304(14)00232-0 [pii] AID - 10.1016/j.cllc.2014.10.003 [doi] PST - ppublish SO - Clin Lung Cancer. 2015 Mar;16(2):106-11. doi: 10.1016/j.cllc.2014.10.003. Epub 2014 Oct 24.