PMID- 34509095
OWN - NLM
STAT- MEDLINE
DCOM- 20211022
LR  - 20211204
IS  - 1872-8332 (Electronic)
IS  - 0169-5002 (Linking)
VI  - 160
DP  - 2021 Oct
TI  - Canadian ROS proto-oncogene 1 study (CROS) for multi-institutional implementation 
      of ROS1 testing in non-small cell lung cancer.
PG  - 127-135
LID - S0169-5002(21)00490-6 [pii]
LID - 10.1016/j.lungcan.2021.08.003 [doi]
AB  - Patients with non-small cell lung cancer (NSCLC) harboring ROS proto-oncogene 1 
      (ROS1) gene rearrangements show dramatic response to the tyrosine kinase 
      inhibitor (TKI) crizotinib. Current best practice guidelines recommend that all 
      advanced stage non-squamous NSCLC patients be also tested for ROS1 gene 
      rearrangements. Several studies have suggested that ROS1 immunohistochemistry 
      (IHC) using the D4D6 antibody may be used to screen for ROS1 fusion positive lung 
      cancers, with assays showing high sensitivity but moderate to high specificity. A 
      break apart fluorescence in situ hybridization (FISH) test is then used to 
      confirm the presence of ROS1 gene rearrangement. The goal of Canadian ROS1 (CROS) 
      study was to harmonize ROS1 laboratory developed testing (LDT) by using IHC and 
      FISH assays to detect ROS1 rearranged lung cancers across Canadian pathology 
      laboratories. Cell lines expressing different levels of ROS1 (high, low, none) 
      were used to calibrate IHC protocols after which participating laboratories ran 
      the calibrated protocols on a reference set of 24 NSCLC cases (9 ROS1 rearranged 
      tumors and 15 ROS1 non-rearranged tumors as determined by FISH). Results were 
      compared using a centralized readout. The stained slides were evaluated for the 
      cellular localization of staining, intensity of staining, the presence of 
      staining in non-tumor cells, the presence of non-specific staining (e.g. 
      necrosis, extracellular mater, other) and the percent positive cells. H-score was 
      also determined for each tumor. Analytical sensitivity and specificity 
      harmonization was achieved by using low limit of detection (LOD) as either any 
      positivity in the U118 cell line or H-score of 200 with the HCC78 cell line. An 
      overall diagnostic sensitivity and specificity of up to 100% and 99% respectively 
      was achieved for ROS1 IHC testing (relative to FISH) using an adjusted H-score 
      readout on the reference cases. This study confirms that LDT ROS1 IHC assays can 
      be highly sensitive and specific for detection of ROS1 rearrangements in NSCLC. 
      As NSCLC can demonstrate ROS1 IHC positivity in FISH-negative cases, the degree 
      of the specificity of the IHC assay, especially in highly sensitive protocols, is 
      mostly dependent on the readout cut-off threshold. As ROS1 IHC is a screening 
      assay for a rare rearrangements in NSCLC, we recommend adjustment of the readout 
      threshold in order to balance specificity, rather than decreasing the overall 
      analytical and diagnostic sensitivity of the protocols.
CI  - Crown Copyright (c) 2021. Published by Elsevier B.V. All rights reserved.
FAU - Cheung, Carol C
AU  - Cheung CC
AD  - Laboratory Medicine Program, University Health Network, Toronto, ON, Canada; 
      Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, 
      University of Toronto, Toronto, ON, Canada.
FAU - Smith, Adam C
AU  - Smith AC
AD  - Laboratory Medicine Program, University Health Network, Toronto, ON, Canada; 
      Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, 
      University of Toronto, Toronto, ON, Canada.
FAU - Albadine, Roula
AU  - Albadine R
AD  - Department of Pathology, Centre hospitalier de l'Universite de Montreal, 
      Montreal, QC, Canada.
FAU - Bigras, Gilbert
AU  - Bigras G
AD  - Laboratory Medicine Department, University of Alberta, Edmonton, AB, Canada.
FAU - Bojarski, Anna
AU  - Bojarski A
AD  - Department of Pathology and Laboratory Medicine, Health Sciences North, Sudbury, 
      ON, Canada.
FAU - Couture, Christian
AU  - Couture C
AD  - Institut universitaire de cardiologie et de pneumologie de Quebec-Universite 
      Laval, Quebec City, QC, Canada.
FAU - Cutz, Jean-Claude
AU  - Cutz JC
AD  - Department of Pathology and Molecular Medicine, McMaster University Health 
      Sciences Centre and McMaster University, Hamilton, ON, Canada.
FAU - Huang, Weei-Yuan
AU  - Huang WY
AD  - Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, 
      University of Toronto, Toronto, ON, Canada; Department of Laboratory Medicine and 
      Molecular Diagnostics, Sunnybrook Health Science Center, ON, Canada.
FAU - Ionescu, Diana
AU  - Ionescu D
AD  - Department of Pathology and Laboratory Medicine, BC Cancer, Vancouver, BC, 
      Canada.
FAU - Itani, Doha
AU  - Itani D
AD  - Department of Pathology and Laboratory Medicine, Cumming School of Medicine, 
      University of Calgary, Calgary, AB, Canada; Department of Pathology, Department 
      of Pathology and Laboratory Medicine, Medical College of Wisconsin, Milwaukee, 
      WI, USA.
FAU - Izevbaye, Iyare
AU  - Izevbaye I
AD  - Laboratory Medicine Department, University of Alberta, Edmonton, AB, Canada.
FAU - Karsan, Aly
AU  - Karsan A
AD  - Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC, Canada.
FAU - Kelly, Margaret M
AU  - Kelly MM
AD  - Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, 
      Alberta, Canada.
FAU - Knoll, Joan
AU  - Knoll J
AD  - Department of Pathology and Laboratory Medicine, London Health Sciences Centre, 
      London, Ontario, Canada.
FAU - Kwan, Keith
AU  - Kwan K
AD  - Department of Pathology and Laboratory Medicine, London Health Sciences Centre, 
      London, Ontario, Canada.
FAU - Nasr, Michel R
AU  - Nasr MR
AD  - Department of Pathology, Shared Health Manitoba, University of Manitoba, 
      Winnipeg, MB, Canada; Department of Pathology SUNY Upstate Medical University, 
      Syracuse, NY, USA.
FAU - Qing, Gefei
AU  - Qing G
AD  - Department of Pathology and Laboratory Medicine, Cumming School of Medicine, 
      University of Calgary, AB, Canada, and Calgary Laboratory Services, Calgary, AB, 
      Canada.
FAU - Rashid-Kolvear, Fariboz
AU  - Rashid-Kolvear F
AD  - Department of Pathology and Laboratory Medicine, Cumming School of Medicine, 
      University of Calgary, AB, Canada, and Calgary Laboratory Services, Calgary, AB, 
      Canada; Department of Pathology and Laboratory Medicine, Johns Hopkins Medicine, 
      Johns Hopkins All Children's Hospital, Baltimore, MD, USA.
FAU - Sekhon, Harmanjatinder S
AU  - Sekhon HS
AD  - Department of Pathology and Laboratory Medicine, The Ottawa Hospital and ORLA, 
      University of Ottawa, Ottawa, ON, Canada.
FAU - Spatz, Alan
AU  - Spatz A
AD  - Divisions of Pathology and Molecular Genetics, McGill University Health Center 
      and McGill University, Montreal, QC, Canada.
FAU - Stockley, Tracy
AU  - Stockley T
AD  - Laboratory Medicine Program, University Health Network, Toronto, ON, Canada; 
      Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, 
      University of Toronto, Toronto, ON, Canada.
FAU - Tran-Thanh, Danh
AU  - Tran-Thanh D
AD  - Department of Pathology, Centre hospitalier de l'Universite de Montreal, 
      Montreal, QC, Canada.
FAU - Tucker, Tracy
AU  - Tucker T
AD  - Department of Pathology and Laboratory Medicine, BC Cancer, Vancouver, BC, 
      Canada.
FAU - Waghray, Ranjit
AU  - Waghray R
AD  - Department of Pathology and Laboratory Medicine, Cumming School of Medicine, 
      University of Calgary, Calgary, AB, Canada.
FAU - Wang, Hangjun
AU  - Wang H
AD  - Divisions of Pathology and Molecular Genetics, McGill University Health Center 
      and McGill University, Montreal, QC, Canada.
FAU - Xu, Zhaolin
AU  - Xu Z
AD  - Dept. of Pathology, Queen Elizabeth II Health Sciences Centre and Dalhousie 
      University, Halifax, NS, Canada.
FAU - Yatabe, Yasushi
AU  - Yatabe Y
AD  - Department of Diagnostic Pathology, National Cancer Center, Tokyo, Japan.
FAU - Torlakovic, Emina E
AU  - Torlakovic EE
AD  - Department of Pathology and Laboratory Medicine, College of Medicine, University 
      of Saskatchewan and Saskatchewan Health Authority, Saskatoon, SK, Canada. 
      Electronic address: emina.torlakovic@usask.ca.
FAU - Tsao, Ming-Sound
AU  - Tsao MS
AD  - Laboratory Medicine Program, University Health Network, Toronto, ON, Canada; 
      Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, 
      University of Toronto, Toronto, ON, Canada.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210810
PL  - Ireland
TA  - Lung Cancer
JT  - Lung cancer (Amsterdam, Netherlands)
JID - 8800805
RN  - 0 (MAS1 protein, human)
RN  - 0 (Proto-Oncogene Mas)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Reactive Oxygen Species)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (ROS1 protein, human)
SB  - IM
MH  - Canada
MH  - *Carcinoma, Non-Small-Cell Lung/diagnosis/genetics
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - *Lung Neoplasms/diagnosis/genetics
MH  - Protein-Tyrosine Kinases/genetics
MH  - Proto-Oncogene Mas
MH  - Proto-Oncogene Proteins/genetics
MH  - Proto-Oncogenes
MH  - Reactive Oxygen Species
OTO - NOTNLM
OT  - Biomarker testing
OT  - FISH
OT  - Immunohistochemistry
OT  - Non-small cell lung cancer
OT  - Quality assurance
OT  - ROS1
EDAT- 2021/09/12 06:00
MHDA- 2023/02/25 06:00
CRDT- 2021/09/11 20:21
PHST- 2021/04/23 00:00 [received]
PHST- 2021/07/23 00:00 [revised]
PHST- 2021/08/03 00:00 [accepted]
PHST- 2021/09/12 06:00 [pubmed]
PHST- 2023/02/25 06:00 [medline]
PHST- 2021/09/11 20:21 [entrez]
AID - S0169-5002(21)00490-6 [pii]
AID - 10.1016/j.lungcan.2021.08.003 [doi]
PST - ppublish
SO  - Lung Cancer. 2021 Oct;160:127-135. doi: 10.1016/j.lungcan.2021.08.003. Epub 2021 
      Aug 10.