PMID- 30529852
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 1936-5233 (Print)
IS  - 1936-5233 (Electronic)
IS  - 1936-5233 (Linking)
VI  - 12
IP  - 2
DP  - 2019 Feb
TI  - Discordance between FISH, IHC, and NGS Analysis of ALK Status in Advanced 
      Non-Small Cell Lung Cancer (NSCLC): a Brief Report of 7 Cases.
PG  - 389-395
LID - S1936-5233(18)30485-6 [pii]
LID - 10.1016/j.tranon.2018.11.006 [doi]
AB  - BACKGROUND: Anaplastic lymphoma kinase (ALK) rearrangement represents a landmark 
      in the targeted therapy of non-small cell lung cancer (NSCLC). 
      Immunohistochemistry (IHC) is a sensitive and specific method to detect ALK 
      protein expression, possibly an alternative to fluorescence in situ hybridization 
      (FISH). In this study, the concordance of FISH and IHC to determine ALK status 
      was evaluated, particularly focusing on discordant cases. MATERIALS AND METHODS: 
      ALK status was tested by FISH and the IHC validated method (Ventana ALK (D5F3) 
      CDx Assay) in 95 NSCLCs. Discordant cases were analyzed also by next-generation 
      sequencing (NGS). The response to crizotinib of treated patients was recorded. 
      RESULTS: Seven (7.3%) discordant cases were ALK FISH positive and IHC negative. 
      They showed coexistent split signals pattern, with mean percentage of 15.4%, and 
      5' deletions pattern, with mean percentage 31.7%. Two cases had also gene 
      amplification pattern. In three cases (42.8 %), the polysomy was observed. The 
      NGS assay confirmed IHC results. In these patients, the treatment with crizotinib 
      was ineffective. CONCLUSIONS: In our discordant cases, a coexistent complex 
      pattern (deleted, split, and amplified/polysomic) of ALK gene was observed by 
      FISH analysis. These complex rearranged cases were not detectable by IHC, and it 
      could be speculated that more complex biological mechanisms could modulate 
      protein expression. These data highlight the role of IHC and underscore the 
      complexity of the genetic pattern of ALK. It could be crucial to consider these 
      findings in order to best select patients for anti-ALK treatment in daily 
      clinical practice.
CI  - Copyright (c) 2018 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Scattone, Anna
AU  - Scattone A
AD  - Pathology Department, IRCCS Istituto Tumori "Giovanni Paolo II" di Bari, viale 
      Orazio Flacco 65, 70124 Bari, Italy.
FAU - Catino, Annamaria
AU  - Catino A
AD  - Medical Oncology Unit, IRCCS Istituto Tumori "Giovanni Paolo II" di Bari, viale 
      Orazio Flacco 65, 70124 Bari, Italy.
FAU - Schirosi, Laura
AU  - Schirosi L
AD  - Pathology Department, IRCCS Istituto Tumori "Giovanni Paolo II" di Bari, viale 
      Orazio Flacco 65, 70124 Bari, Italy. Electronic address: 
      l.schirosi@oncologico.bari.it.
FAU - Caldarola, Lucia
AU  - Caldarola L
AD  - Pathology Department, Hospital "SS Annunziata", via Bruno 1, 74121 Taranto, 
      Italy.
FAU - Tommasi, Stefania
AU  - Tommasi S
AD  - Molecular Genetic Laboratory, IRCCS Istituto Tumori "Giovanni Paolo II" di Bari, 
      viale Orazio Flacco 65, 70124 Bari, Italy.
FAU - Lacalamita, Rosanna
AU  - Lacalamita R
AD  - Molecular Genetic Laboratory, IRCCS Istituto Tumori "Giovanni Paolo II" di Bari, 
      viale Orazio Flacco 65, 70124 Bari, Italy.
FAU - Montagna, Elisabetta Sara
AU  - Montagna ES
AD  - Medical Oncology Unit, IRCCS Istituto Tumori "Giovanni Paolo II" di Bari, viale 
      Orazio Flacco 65, 70124 Bari, Italy.
FAU - Galetta, Domenico
AU  - Galetta D
AD  - Medical Oncology Unit, IRCCS Istituto Tumori "Giovanni Paolo II" di Bari, viale 
      Orazio Flacco 65, 70124 Bari, Italy.
FAU - Serio, Gabriella
AU  - Serio G
AD  - Pathology Department, DETO, University of Bari, piazza Giulio Cesare, Bari 70124, 
      Italy.
FAU - Zito, Francesco Alfredo
AU  - Zito FA
AD  - Pathology Department, IRCCS Istituto Tumori "Giovanni Paolo II" di Bari, viale 
      Orazio Flacco 65, 70124 Bari, Italy.
FAU - Mangia, Anita
AU  - Mangia A
AD  - Functional Biomorphology Laboratory, IRCCS Istituto Tumori "Giovanni Paolo II" di 
      Bari, viale Orazio Flacco 65, 70124 Bari, Italy.
LA  - eng
PT  - Journal Article
DEP - 20181204
PL  - United States
TA  - Transl Oncol
JT  - Translational oncology
JID - 101472619
PMC - PMC6280637
EDAT- 2018/12/12 06:00
MHDA- 2018/12/12 06:01
PMCR- 2018/12/04
CRDT- 2018/12/12 06:00
PHST- 2018/09/26 00:00 [received]
PHST- 2018/11/13 00:00 [revised]
PHST- 2018/11/13 00:00 [accepted]
PHST- 2018/12/12 06:00 [pubmed]
PHST- 2018/12/12 06:01 [medline]
PHST- 2018/12/12 06:00 [entrez]
PHST- 2018/12/04 00:00 [pmc-release]
AID - S1936-5233(18)30485-6 [pii]
AID - 10.1016/j.tranon.2018.11.006 [doi]
PST - ppublish
SO  - Transl Oncol. 2019 Feb;12(2):389-395. doi: 10.1016/j.tranon.2018.11.006. Epub 
      2018 Dec 4.