PMID- 38240952
OWN - NLM
STAT- MEDLINE
DCOM- 20240122
LR  - 20240201
IS  - 1591-9528 (Electronic)
IS  - 1591-8890 (Print)
IS  - 1591-8890 (Linking)
VI  - 24
IP  - 1
DP  - 2024 Jan 19
TI  - Evaluation of NTRK expression and fusions in a large cohort of early-stage lung 
      cancer.
PG  - 10
LID - 10.1007/s10238-023-01273-0 [doi]
LID - 10
AB  - Tropomyosin receptor kinases (TRK) are attractive targets for cancer therapy. As 
      TRK-inhibitors are approved for all solid cancers with detectable fusions 
      involving the Neurotrophic tyrosine receptor kinase (NTRK)-genes, there has been 
      an increased interest in optimizing testing regimes. In this project, we wanted 
      to find the prevalence of NTRK fusions in a cohort of various histopathological 
      types of early-stage lung cancer in Norway and to investigate the association 
      between TRK protein expression and specific histopathological types, including 
      their molecular and epidemiological characteristics. We used immunohistochemistry 
      (IHC) as a screening tool for TRK expression, and next-generation sequencing 
      (NGS) and fluorescence in situ hybridization (FISH) as confirmatory tests for 
      underlying NTRK-fusion. Among 940 cases, 43 (4.6%) had positive TRK IHC, but in 
      none of these could a NTRK fusion be confirmed by NGS or FISH. IHC-positive cases 
      showed various staining intensities and patterns including cytoplasmatic or 
      nuclear staining. IHC-positivity was more common in squamous cell carcinoma 
      (LUSC) (10.3%) and adenoid cystic carcinoma (40.0%), where the majority showed 
      heterogeneous staining intensity. In comparison, only 1.1% of the adenocarcinomas 
      were positive. IHC-positivity was also more common in men, but this association 
      could be explained by the dominance of LUSC in TRK IHC-positive cases. Protein 
      expression was not associated with differences in time to relapse or overall 
      survival. Our study indicates that NTRK fusion is rare in early-stage lung 
      cancer. Due to the high level of false positive cases with IHC, Pan-TRK IHC is 
      less suited as a screening tool for NTRK-fusions in LUSC and adenoid cystic 
      carcinoma.
CI  - (c) 2024. The Author(s).
FAU - Dyrbekk, Anne Pernille Harlem
AU  - Dyrbekk APH
AUID- ORCID: 0009-0008-7930-9153
AD  - University of Oslo, NO-0316, Oslo, Norway. anndyr@siv.no.
AD  - Department of Pathology, Vestfold Hospital Trust, NO-3103, Tonsberg, Norway. 
      anndyr@siv.no.
AD  - Department of Cancer Genetics, Institute for Cancer Research, The Norwegian 
      Radium Hospital, NO-0310, Oslo, Norway. anndyr@siv.no.
FAU - Warsame, Abdirashid Ali
AU  - Warsame AA
AD  - Department of Pathology, Oslo University Hospital, The Norwegian Radium Hospital, 
      NO-0310, Oslo, Norway.
FAU - Suhrke, Pal
AU  - Suhrke P
AUID- ORCID: 0000-0002-3133-5503
AD  - Department of Pathology, Vestfold Hospital Trust, NO-3103, Tonsberg, Norway.
FAU - Ludahl, Marianne Odnakk
AU  - Ludahl MO
AD  - Department of Microbiology/Division for Gene-Technology, Vestfold Hospital Trust, 
      NO-3103, Tonsberg, Norway.
FAU - Zecic, Nermin
AU  - Zecic N
AUID- ORCID: 0009-0008-0687-424X
AD  - Department of Microbiology/Division for Gene-Technology, Vestfold Hospital Trust, 
      NO-3103, Tonsberg, Norway.
FAU - Moe, Joakim Oliu
AU  - Moe JO
AUID- ORCID: 0009-0001-9680-6329
AD  - Department of Internal Medicine, Vestfold Hospital Trust, NO-3103, Tonsberg, 
      Norway.
FAU - Lund-Iversen, Marius
AU  - Lund-Iversen M
AUID- ORCID: 0000-0002-2025-4062
AD  - Department of Pathology, Oslo University Hospital, The Norwegian Radium Hospital, 
      NO-0310, Oslo, Norway.
FAU - Brustugun, Odd Terje
AU  - Brustugun OT
AUID- ORCID: 0000-0002-5153-8391
AD  - University of Oslo, NO-0316, Oslo, Norway.
AD  - Department of Cancer Genetics, Institute for Cancer Research, The Norwegian 
      Radium Hospital, NO-0310, Oslo, Norway.
AD  - Department of Oncology, Vestre Viken Hospital Trust, NO-3004, Drammen, Norway.
LA  - eng
GR  - 2022020/The South-Eastern Norway Regional Health Authority/
GR  - 198223/The Research fund Vestfold Hospital Trust/
GR  - 2018049/South-Eastern Norway Regional Health Authority/
PT  - Journal Article
DEP - 20240119
PL  - Italy
TA  - Clin Exp Med
JT  - Clinical and experimental medicine
JID - 100973405
RN  - EC 2.7.10.1 (Receptor, trkA)
RN  - EC 2.7.10.1 (Receptor, trkC)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - 0 (Oncogene Proteins, Fusion)
SB  - IM
MH  - Male
MH  - Humans
MH  - Receptor, trkA/genetics
MH  - Receptor, trkC/genetics
MH  - Receptor, trkB/genetics
MH  - *Carcinoma, Adenoid Cystic
MH  - In Situ Hybridization, Fluorescence
MH  - *Lung Neoplasms/diagnosis/genetics
MH  - Oncogene Proteins, Fusion/genetics
MH  - Neoplasm Recurrence, Local
MH  - *Neoplasms/diagnosis
PMC - PMC10798916
OTO - NOTNLM
OT  - Fluorescence in situ hybridization
OT  - Immunohistochemistry
OT  - Lung cancer
OT  - Molecular pathology
OT  - NTRK
OT  - Next-generation sequencing
COIS- Odd Terje Brustugun and Anne Pernille Harlem Dyrbekk: Roche Norway has sponsored 
      expenses for immunohistochemical reagents.
EDAT- 2024/01/19 12:43
MHDA- 2024/01/22 06:42
PMCR- 2024/01/19
CRDT- 2024/01/19 11:12
PHST- 2023/10/26 00:00 [received]
PHST- 2023/11/29 00:00 [accepted]
PHST- 2024/01/22 06:42 [medline]
PHST- 2024/01/19 12:43 [pubmed]
PHST- 2024/01/19 11:12 [entrez]
PHST- 2024/01/19 00:00 [pmc-release]
AID - 10.1007/s10238-023-01273-0 [pii]
AID - 1273 [pii]
AID - 10.1007/s10238-023-01273-0 [doi]
PST - epublish
SO  - Clin Exp Med. 2024 Jan 19;24(1):10. doi: 10.1007/s10238-023-01273-0.