PMID- 34534989
OWN - NLM
STAT- MEDLINE
DCOM- 20220316
LR  - 20221013
IS  - 1533-4058 (Electronic)
IS  - 1533-4058 (Linking)
VI  - 30
IP  - 1
DP  - 2022 Jan 1
TI  - Histologic and Molecular Characterization of Non-Small Cell Lung Carcinoma With 
      Discordant ROS1 Immunohistochemistry and Fluorescence In Situ Hybridization.
PG  - 19-26
LID - 10.1097/PAI.0000000000000973 [doi]
AB  - INTRODUCTION: ROS1 immunohistochemical (IHC) positivity requires follow-up with 
      confirmatory testing such as fluorescence in situ hybridization (FISH). 
      Identifying predictive characteristics of false positive ROS1 IHC cases could aid 
      in optimizing testing algorithms, decrease testing costs and preserve tissue. 
      MATERIALS AND METHODS: Retrospective results were retrieved for 2054 patients 
      with non-small cell lung carcinoma submitted to our laboratory for molecular 
      testing. Reflex ROS1 FISH was done on all ROS1 immunoreactive cases using ROS1 
      D4D6 antibody. Staining intensity and histo-score was recorded for all ROS1 
      immunoreactive cases. Results of any additional molecular testing (KRAS, BRAF, 
      EGFR, ALK FISH, RET FISH, MET FISH) were also tabulated. RESULTS: ROS1 
      immunoreactivity was seen in 305/2054 (14.8%) cases. Immunoreactivity was weak in 
      majority of the cases with only 4.6% cases having an histo-score >100 and 5.9% of 
      cases had moderate staining intensity. FISH was negative in 99% (302/305) cases 
      with any degree of IHC expression (discordant cases) while 3 cases were positive 
      by FISH. Diffuse strong IHC staining in greater than 90% of the tumor was noted 
      in 6 cases, 3 (0.98%) of which were confirmed to have ROS1 rearrangement by FISH. 
      The discordant cases had significantly higher rates of EGFR mutations (P<0.0005) 
      in comparison to ROS1 IHC negative cases, were seen more often in adenocarcinoma 
      and adenosquamous cell carcinoma (P<0.0005) with lepidic and acinar patterns, and 
      more likely to occur in primary lung carcinomas (P<0.0005). CONCLUSIONS: False 
      positive ROS1 immunoreactivity was very frequent, occurred more commonly in 
      primary NSCLC cases with acinar and/or lepidic histologies and was more likely in 
      EGFR mutated cases. Using higher positivity thresholds for ROS1 IHC and 
      incorporating the histologic and molecular correlates into algorithmic strategies 
      could result in increased specificity and clinical utility of ROS1 IHC assay.
CI  - Copyright (c) 2021 Wolters Kluwer Health, Inc. All rights reserved.
FAU - Wilcock, Diane M
AU  - Wilcock DM
AD  - University of Utah and ARUP Laboratories, Salt Lake City, UT.
FAU - Schmidt, Robert L
AU  - Schmidt RL
AD  - University of Utah and ARUP Laboratories, Salt Lake City, UT.
FAU - Furtado, Larissa V
AU  - Furtado LV
AD  - St. Jude Childrens' Research Hospital, Memphis, TN.
FAU - Matynia, Anna P
AU  - Matynia AP
AD  - University of Utah and ARUP Laboratories, Salt Lake City, UT.
FAU - Deftereos, Georgios
AU  - Deftereos G
AD  - University of Utah and ARUP Laboratories, Salt Lake City, UT.
FAU - Sirohi, Deepika
AU  - Sirohi D
AD  - University of Utah and ARUP Laboratories, Salt Lake City, UT.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Appl Immunohistochem Mol Morphol
JT  - Applied immunohistochemistry & molecular morphology : AIMM
JID - 100888796
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  - *Carcinoma, Non-Small-Cell Lung/diagnosis/genetics
MH  - Gene Rearrangement
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence/methods
MH  - *Lung Neoplasms/diagnosis/genetics/pathology
MH  - Protein-Tyrosine Kinases/genetics
MH  - Proto-Oncogene Proteins/genetics/metabolism
MH  - Retrospective Studies
COIS- The authors declare no conflict of interest.
EDAT- 2021/09/18 06:00
MHDA- 2022/03/17 06:00
CRDT- 2021/09/17 20:29
PHST- 2021/05/06 00:00 [received]
PHST- 2021/08/19 00:00 [accepted]
PHST- 2021/09/18 06:00 [pubmed]
PHST- 2022/03/17 06:00 [medline]
PHST- 2021/09/17 20:29 [entrez]
AID - 00129039-202201000-00004 [pii]
AID - 10.1097/PAI.0000000000000973 [doi]
PST - ppublish
SO  - Appl Immunohistochem Mol Morphol. 2022 Jan 1;30(1):19-26. doi: 
      10.1097/PAI.0000000000000973.