PMID- 37143440
OWN - NLM
STAT- MEDLINE
DCOM- 20230804
LR  - 20230809
IS  - 2056-4538 (Electronic)
IS  - 2056-4538 (Linking)
VI  - 9
IP  - 5
DP  - 2023 Sep
TI  - NTRK gene aberrations in triple-negative breast cancer: detection challenges 
      using IHC, FISH, RT-PCR, and NGS.
PG  - 367-377
LID - 10.1002/cjp2.324 [doi]
AB  - Triple-negative breast cancer (TNBC) is usually an aggressive disease with a poor 
      prognosis and limited treatment options. The neurotrophic tyrosine receptor 
      kinase (NTRK) gene fusions are cancer type-agnostic emerging biomarkers approved 
      by the Food and Drug Administration (FDA), USA, for the selection of patients for 
      targeted therapy. The main aim of our study was to investigate the frequency of 
      NTRK aberrations, i.e. fusions, gene copy number gain, and amplification, in a 
      series of TNBC using different methods. A total of 83 TNBCs were analyzed using 
      pan-TRK immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), 
      real-time polymerase chain reaction (RT-PCR), and RNA-based next-generation 
      sequencing (NGS). Of 83 cases, 16 showed pan-TRK positivity although no cases had 
      NTRK-fusions. Indeed, FISH showed four cases carrying an atypical NTRK1 pattern 
      consisting of one fusion signal and one/more single green signals, but all cases 
      were negative for fusion by NGS and RT-PCR testing. In addition, FISH analysis 
      showed six cases with NTRK1 amplification, one case with NTRK2 copy number gain, 
      and five cases with NTRK3 copy number gain, all negative for pan-TRK IHC. Our 
      data demonstrate that IHC has a high false-positive rate for the detection of 
      fusions and molecular testing is mandatory; there is no need to perform 
      additional molecular tests in cases negativity for NTRK by IHC. In conclusion, 
      the NTRK genes are not involved in fusions in TNBC, but both copy number gain and 
      amplification are frequent events, suggesting a possible predictive role for 
      other NTRK aberrations.
CI  - (c) 2023 The Authors. The Journal of Pathology: Clinical Research published by The 
      Pathological Society of Great Britain and Ireland and John Wiley & Sons Ltd.
FAU - Zito Marino, Federica
AU  - Zito Marino F
AD  - Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, 
      University of Campania "L. Vanvitelli", Naples, Italy.
FAU - Buono, Simona
AU  - Buono S
AD  - Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, 
      University of Campania "L. Vanvitelli", Naples, Italy.
FAU - Montella, Marco
AU  - Montella M
AD  - Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, 
      University of Campania "L. Vanvitelli", Naples, Italy.
FAU - Giannatiempo, Rosa
AU  - Giannatiempo R
AD  - Ospedale Evangelico Betania, Naples, Italy.
FAU - Messina, Francesco
AU  - Messina F
AD  - Ospedale Evangelico Betania, Naples, Italy.
FAU - Casaretta, Giovanni
AU  - Casaretta G
AD  - Ospedale Evangelico Betania, Naples, Italy.
FAU - Arpino, Grazia
AU  - Arpino G
AD  - Department of Clinical Medicine and Surgery, University of Naples Federico II, 
      Naples, Italy.
FAU - Vita, Giulia
AU  - Vita G
AD  - Anatomical Pathology Department, IRCCS CROB, Rionero in Vulture, Italy.
FAU - Fiorentino, Francesco
AU  - Fiorentino F
AD  - Pathology Unit, S.M. delle Grazie Hospital, Naples, Italy.
FAU - Insabato, Luigi
AU  - Insabato L
AD  - Department of Advanced Biomedical Sciences, Pathology Section, University of 
      Naples "Federico II", Naples, Italy.
FAU - Sgambato, Alessandro
AU  - Sgambato A
AD  - Scientific Direction, Centro di Riferimento Oncologico della Basilicata 
      (IRCCS-CROB), Rionero in Vulture, Italy.
FAU - Orditura, Michele
AU  - Orditura M
AD  - Division of Medical Oncology, Department of Precision Medicine, School of 
      Medicine, University of Campania "L. Vanvitelli", Naples, Italy.
FAU - Franco, Renato
AU  - Franco R
AD  - Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, 
      University of Campania "L. Vanvitelli", Naples, Italy.
FAU - Accardo, Marina
AU  - Accardo M
AD  - Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, 
      University of Campania "L. Vanvitelli", Naples, Italy.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230504
PL  - England
TA  - J Pathol Clin Res
JT  - The journal of pathology. Clinical research
JID - 101658534
RN  - EC 2.7.10.1 (Receptor, trkA)
SB  - IM
MH  - Humans
MH  - *Receptor, trkA/genetics
MH  - *Triple Negative Breast Neoplasms/genetics
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - High-Throughput Nucleotide Sequencing
PMC - PMC10397374
OTO - NOTNLM
OT  - FISH
OT  - IHC
OT  - NGS
OT  - NTRK amplification
OT  - NTRK fusions
OT  - RT-PCR
OT  - neurotrophic tyrosine receptor kinase (NTRK)
OT  - triple-negative breast carcinoma
EDAT- 2023/05/05 06:42
MHDA- 2023/08/04 06:43
PMCR- 2023/05/04
CRDT- 2023/05/05 03:44
PHST- 2023/03/31 00:00 [revised]
PHST- 2022/11/25 00:00 [received]
PHST- 2023/04/07 00:00 [accepted]
PHST- 2023/08/04 06:43 [medline]
PHST- 2023/05/05 06:42 [pubmed]
PHST- 2023/05/05 03:44 [entrez]
PHST- 2023/05/04 00:00 [pmc-release]
AID - CJP2324 [pii]
AID - 10.1002/cjp2.324 [doi]
PST - ppublish
SO  - J Pathol Clin Res. 2023 Sep;9(5):367-377. doi: 10.1002/cjp2.324. Epub 2023 May 4.