PMID- 34746883
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220428
IS  - 2666-3643 (Electronic)
IS  - 2666-3643 (Linking)
VI  - 2
IP  - 10
DP  - 2021 Oct
TI  - ALK Gene Rearrangements in Lung Adenocarcinomas: Concordance of 
      Immunohistochemistry, Fluorescence In Situ Hybridization, RNA In Situ 
      Hybridization, and RNA Next-Generation Sequencing Testing.
PG  - 100223
LID - 10.1016/j.jtocrr.2021.100223 [doi]
LID - 100223
AB  - INTRODUCTION: The 2018 updated molecular testing guidelines for patients with 
      advanced lung cancer incorporated ALK immunohistochemistry (IHC) analysis as an 
      equivalent to fluorescence in situ hybridization (FISH) method recommended in 
      2013. Nevertheless, no specific recommendation for alternative methods was 
      proposed owing to insufficient data. The aim of this study was to compare the 
      results of ALK IHC, FISH, RNA next-generation sequencing (NGS), and RNA in situ 
      hybridization (ISH) with available clinical data. METHODS: A search for lung 
      carcinomas with ALK testing by greater than or equal to one modality (i.e., ALK 
      IHC, FISH, NGS) was performed; a subset underwent RNA ISH. When available, 
      clinical data were recorded. RESULTS: The results were concordant among all 
      performed testing modalities in 86 of 90 cases (95.6%). Of the four discordant 
      cases, two were ALK positive by FISH but negative by IHC, RNA NGS, and RNA ISH. 
      The remaining two cases failed RNA NGS testing, one was IHC negative, FISH 
      positive, RNA ISH negative and the second was IHC positive, FISH positive, RNA 
      ISH equivocal. RNA NGS identified one rare and one novel ALK fusion. Sufficient 
      therapy data were available in 10 cases treated with tyrosine kinase inhibitors; 
      three had disease progression, including one with discordant results (FISH 
      positive, RNA NGS negative, IHC negative, RNA ISH negative) and two with 
      concordant ALK positivity among all modalities. CONCLUSIONS: Our results reveal 
      high concordance among IHC, RNA NGS, and RNA ISH. In cases of discordance with 
      available RNA NGS, FISH result was positive whereas IHC and ISH results were 
      negative. On the basis of our data, multimodality testing is recommended to 
      identify discrepant results and patients (un)likely to respond to tyrosine kinase 
      inhibitors.
CI  - (c) 2021 The Authors.
FAU - Canterbury, Carleigh R
AU  - Canterbury CR
AD  - Department of Pathology and Cell Biology, Columbia University Medical Center, New 
      York, New York.
FAU - Fernandes, Helen
AU  - Fernandes H
AD  - Department of Pathology and Cell Biology, Columbia University Medical Center, New 
      York, New York.
FAU - Crapanzano, John P
AU  - Crapanzano JP
AD  - Department of Pathology and Cell Biology, Columbia University Medical Center, New 
      York, New York.
FAU - Murty, Vundavalli V
AU  - Murty VV
AD  - Department of Pathology and Cell Biology, Columbia University Medical Center, New 
      York, New York.
FAU - Mansukhani, Mahesh M
AU  - Mansukhani MM
AD  - Department of Pathology and Cell Biology, Columbia University Medical Center, New 
      York, New York.
FAU - Shu, Catherine A
AU  - Shu CA
AD  - Division of Hematology/Oncology, Department of Medicine, Columbia University 
      Medical Center, New York, New York.
FAU - Szabolcs, Matthias
AU  - Szabolcs M
AD  - Department of Pathology and Cell Biology, Columbia University Medical Center, New 
      York, New York.
FAU - Saqi, Anjali
AU  - Saqi A
AD  - Department of Pathology and Cell Biology, Columbia University Medical Center, New 
      York, New York.
LA  - eng
PT  - Journal Article
DEP - 20210925
PL  - United States
TA  - JTO Clin Res Rep
JT  - JTO clinical and research reports
JID - 101769967
PMC - PMC8552107
OTO - NOTNLM
OT  - ALK
OT  - Anchored multiplex
OT  - Archer
OT  - Fluorescent in situ hybridization (FISH)
OT  - Next-generation sequencing (NGS)
OT  - RNA in situ hybridization (RNA ISH)
EDAT- 2021/11/09 06:00
MHDA- 2021/11/09 06:01
PMCR- 2021/09/25
CRDT- 2021/11/08 06:58
PHST- 2021/03/22 00:00 [received]
PHST- 2021/08/05 00:00 [revised]
PHST- 2021/08/29 00:00 [accepted]
PHST- 2021/11/08 06:58 [entrez]
PHST- 2021/11/09 06:00 [pubmed]
PHST- 2021/11/09 06:01 [medline]
PHST- 2021/09/25 00:00 [pmc-release]
AID - S2666-3643(21)00082-5 [pii]
AID - 100223 [pii]
AID - 10.1016/j.jtocrr.2021.100223 [doi]
PST - epublish
SO  - JTO Clin Res Rep. 2021 Sep 25;2(10):100223. doi: 10.1016/j.jtocrr.2021.100223. 
      eCollection 2021 Oct.