PMID- 27179848 OWN - NLM STAT- MEDLINE DCOM- 20171106 LR - 20211204 IS - 1556-1380 (Electronic) IS - 1556-0864 (Linking) VI - 11 IP - 7 DP - 2016 Jul TI - A Validation Study for the Use of ROS1 Immunohistochemical Staining in Screening for ROS1 Translocations in Lung Cancer. PG - 1029-39 LID - S1556-0864(16)30082-X [pii] LID - 10.1016/j.jtho.2016.03.019 [doi] AB - INTRODUCTION: The presence of ROS proto-oncogene 1, receptor tyrosine kinase gene (ROS1) rearrangements in lung cancers confers sensitivity to ROS kinase inhibitors, including crizotinib. However, they are rare abnormalities (in approximately 1% of non-small cell lung carcinomas) that are typically identified by fluorescence in situ hybridization (FISH), and so screening using immunohistochemical (IHC) staining would be both cost- and time-efficient. METHODS: A cohort of lung tumors negative for other common mutations related to targeted therapies were screened to assess the sensitivity and specificity of IHC staining in detecting ROS1 gene rearrangements, enriched by four other cases first identified by FISH. A review of published data was also undertaken. RESULTS: IHC staining was 100% sensitive (95% confidence interval: 48-100) and 83% specific (95% confidence interval: 86-100) overall when an h-score higher than 100 was used. Patients with ROS1 gene rearrangements were younger and typically never-smokers, with the tumors all being adenocarcinomas with higher-grade architectural features and focal signet ring morphologic features (two of five). Four patients treated with crizotinib showed a partial response, with three also showing a partial response to pemetrexed. Three of four patients remain alive at 13, 27, and 31 months, respectively. CONCLUSION: IHC staining can be used to screen for ROS1 gene rearrangements, with patients herein showing a response to crizotinib. Patients with tumors that test positive according to IHC staining but negative according to FISH were also identified, which may have implications for treatment selection. CI - Copyright (c) 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved. FAU - Viola, Patrizia AU - Viola P AD - Department of Histopathology, Royal Brompton and Harefield National Health Service Foundation Trust, London, United Kingdom. FAU - Maurya, Manisha AU - Maurya M AD - Centre for Molecular Pathology, Royal Marsden Hospital, Sutton, United Kingdom. FAU - Croud, James AU - Croud J AD - Department of Histopathology, Royal Brompton and Harefield National Health Service Foundation Trust, London, United Kingdom. FAU - Gazdova, Jana AU - Gazdova J AD - Centre for Molecular Pathology, Royal Marsden Hospital, Sutton, United Kingdom. FAU - Suleman, Nadia AU - Suleman N AD - Department of Histopathology, Royal Brompton and Harefield National Health Service Foundation Trust, London, United Kingdom. FAU - Lim, Eric AU - Lim E AD - Department of Thoracic Surgery, Royal Brompton and Harefield National Health Service Foundation Trust, London, United Kingdom; National Heart and Lung Institute, Imperial College, London, United Kingdom. FAU - Newsom-Davis, Tom AU - Newsom-Davis T AD - Department of Oncology, Chelsea and Westminster Hospital, London, United Kingdom. FAU - Plowman, Nick AU - Plowman N AD - Department of Oncology, St Bartholomew's Hospital, London, United Kingdom. FAU - Rice, Alexandra AU - Rice A AD - Department of Histopathology, Royal Brompton and Harefield National Health Service Foundation Trust, London, United Kingdom; National Heart and Lung Institute, Imperial College, London, United Kingdom. FAU - Montero, M Angeles AU - Montero MA AD - Department of Histopathology, Royal Brompton and Harefield National Health Service Foundation Trust, London, United Kingdom; National Heart and Lung Institute, Imperial College, London, United Kingdom. FAU - Gonzalez de Castro, David AU - Gonzalez de Castro D AD - Centre for Molecular Pathology, Royal Marsden Hospital, Sutton, United Kingdom. FAU - Popat, Sanjay AU - Popat S AD - Department of Medicine, Royal Marsden Hospital, London, United Kingdom. FAU - Nicholson, Andrew G AU - Nicholson AG AD - Department of Histopathology, Royal Brompton and Harefield National Health Service Foundation Trust, London, United Kingdom; National Heart and Lung Institute, Imperial College, London, United Kingdom. Electronic address: a.nicholson@rbht.nhs.uk. LA - eng PT - Journal Article PT - Validation Study DEP - 20160511 PL - United States TA - J Thorac Oncol JT - Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer JID - 101274235 RN - 0 (MAS1 protein, human) RN - 0 (Proto-Oncogene Mas) RN - 0 (Proto-Oncogene Proteins) RN - 0 (Pyrazoles) RN - 0 (Pyridines) RN - 53AH36668S (Crizotinib) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) RN - EC 2.7.10.1 (ROS1 protein, human) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Cohort Studies MH - Crizotinib MH - Female MH - *Gene Rearrangement MH - Humans MH - Immunohistochemistry MH - In Situ Hybridization, Fluorescence MH - Lung Neoplasms/chemistry/drug therapy/*genetics MH - Male MH - Middle Aged MH - Protein-Tyrosine Kinases/analysis/*genetics MH - Proto-Oncogene Mas MH - Proto-Oncogene Proteins/analysis/*genetics MH - Pyrazoles/therapeutic use MH - Pyridines/therapeutic use OTO - NOTNLM OT - FISH OT - Immunohistochemistry OT - Lung cancer OT - ROS1 gene rearrangement EDAT- 2016/05/18 06:00 MHDA- 2017/11/07 06:00 CRDT- 2016/05/16 06:00 PHST- 2016/01/14 00:00 [received] PHST- 2016/03/17 00:00 [revised] PHST- 2016/03/31 00:00 [accepted] PHST- 2016/05/16 06:00 [entrez] PHST- 2016/05/18 06:00 [pubmed] PHST- 2017/11/07 06:00 [medline] AID - S1556-0864(16)30082-X [pii] AID - 10.1016/j.jtho.2016.03.019 [doi] PST - ppublish SO - J Thorac Oncol. 2016 Jul;11(7):1029-39. doi: 10.1016/j.jtho.2016.03.019. Epub 2016 May 11.