PMID- 33301751
OWN - NLM
STAT- MEDLINE
DCOM- 20210906
LR  - 20210906
IS  - 1532-8392 (Electronic)
IS  - 0046-8177 (Linking)
VI  - 109
DP  - 2021 Mar
TI  - Pan-tropomyosin receptor kinase immunoreactivity, ETV6-NTRK3 fusion subtypes, and 
      RET rearrangement in salivary secretory carcinoma.
PG  - 37-44
LID - S0046-8177(20)30243-4 [pii]
LID - 10.1016/j.humpath.2020.11.017 [doi]
AB  - Salivary secretory carcinoma (SASC) is frequently associated with 
      ETV6-neurotrophic tyrosine receptor kinase (NTRK) 3 fusion and more rarely with 
      RET, MET, or ALK rearrangement. We aimed to elucidate the potential diagnostic 
      utility of pan-tropomyosin receptor kinase (Trk) immunohistochemistry and its 
      relationship with the fusion gene subtype in SASC. We examined 33 cases of SASC 
      for immunoexpression of pan-Trk, ALK and ROS1, and gene rearrangement of the 
      ETV6, NTRK3, and RET genes using fluorescence in situ hybridization (FISH) and 
      reverse transcription-polymerase chain reaction (RT-PCR). Thirty (90.9%) of 33 
      SASCs harbored ETV6-NTRK3 fusion gene transcripts by RT-PCR and/or both ETV6 and 
      NTRK3 gene rearrangements by FISH, and 3 cases (9.1%) had RET gene rearrangement. 
      Most NTRK3-rearranged SASCs (27/33 cases; 81.8%) had conventional ETV6 exon 
      5-NTRK3 exon 15 fusion, whereas 2 cases (6.1%) had both the conventional fusion 
      and a novel ETV6 exon 4-NTRK3 exon 15 fusion variant. In the remaining one case 
      (3%), only FISH revealed both ETV6 and NTRK3 rearrangements, suggesting an 
      ETV6-NTRK3 fusion with an as yet undetermined break point. All 30 SASCs with 
      ETV6-NTRK3 fusion and/or NTRK3 rearrangement showed nuclear and cytoplasmic 
      immunoreactivity for pan-Trk. In contrast, 3 SASCs with RET rearrangement showed 
      negative or only weak cytoplasmic staining for pan-Trk. There was no case 
      harboring ALK and ROS1 rearrangements. All 17 non-SASC tumors were negative for 
      pan-Trk. The results suggest that nuclear and cytoplasmic immunoreactivity for 
      pan-TRK may be helpful to identify ETV6-NTRK3-fused SASCs and to distinguish them 
      from RET-rearranged SASCs and morphological mimics.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Yamamoto, Hidetaka
AU  - Yamamoto H
AD  - Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu 
      University, Fukuoka, 812-8582 Japan. Electronic address: 
      hidetaka@surgpath.med.kyushu-u.ac.jp.
FAU - Nozaki, Yui
AU  - Nozaki Y
AD  - Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu 
      University, Fukuoka, 812-8582 Japan.
FAU - Sugii, Azusa
AU  - Sugii A
AD  - Departments of Pathology, National Kyushu Cancer Center, Fukuoka, 811-1395 Japan.
FAU - Taguchi, Kenichi
AU  - Taguchi K
AD  - Departments of Pathology, National Kyushu Cancer Center, Fukuoka, 811-1395 Japan.
FAU - Hongo, Takahiro
AU  - Hongo T
AD  - Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu 
      University, Fukuoka, 812-8582 Japan; Department of Otorhinolaryngology, Graduate 
      School of Medical Sciences, Kyushu University, Fukuoka, 812-8582 Japan.
FAU - Jiromaru, Rina
AU  - Jiromaru R
AD  - Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu 
      University, Fukuoka, 812-8582 Japan; Department of Otorhinolaryngology, Graduate 
      School of Medical Sciences, Kyushu University, Fukuoka, 812-8582 Japan.
FAU - Sato, Masanobu
AU  - Sato M
AD  - Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu 
      University, Fukuoka, 812-8582 Japan.
FAU - Nakano, Takafumi
AU  - Nakano T
AD  - Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu 
      University, Fukuoka, 812-8582 Japan.
FAU - Hashimoto, Kazuki
AU  - Hashimoto K
AD  - Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu 
      University, Fukuoka, 812-8582 Japan.
FAU - Fujiwara, Minako
AU  - Fujiwara M
AD  - Departments of Pathology, National Kyushu Medical Center, Fukuoka, 810-8563 
      Japan.
FAU - Oda, Yoshinao
AU  - Oda Y
AD  - Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu 
      University, Fukuoka, 812-8582 Japan.
LA  - eng
PT  - Journal Article
DEP - 20201207
PL  - United States
TA  - Hum Pathol
JT  - Human pathology
JID - 9421547
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (ETV6-NTRK3 fusion protein, human)
RN  - 0 (Oncogene Proteins, Fusion)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Tropomyosin)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-ret)
RN  - EC 2.7.10.1 (RET protein, human)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - Secretory breast carcinoma
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Biomarkers, Tumor/analysis
MH  - Breast Neoplasms/genetics/*immunology/metabolism
MH  - Carcinoma/genetics/*immunology/metabolism
MH  - Child
MH  - Female
MH  - Gene Rearrangement/genetics
MH  - Humans
MH  - Immunohistochemistry/methods
MH  - Middle Aged
MH  - Oncogene Proteins, Fusion/genetics/*immunology/metabolism
MH  - Protein-Tyrosine Kinases/genetics
MH  - Proto-Oncogene Proteins/genetics
MH  - Proto-Oncogene Proteins c-ret/genetics/*immunology/metabolism
MH  - Receptor Protein-Tyrosine Kinases/genetics
MH  - Salivary Gland Neoplasms/genetics/immunology/pathology
MH  - Tropomyosin/genetics
MH  - Young Adult
OTO - NOTNLM
OT  - NTRK3
OT  - Pan-Trk
OT  - RET
OT  - Salivary
OT  - Secretory carcinoma
EDAT- 2020/12/11 06:00
MHDA- 2021/09/07 06:00
CRDT- 2020/12/10 20:09
PHST- 2020/10/06 00:00 [received]
PHST- 2020/11/26 00:00 [revised]
PHST- 2020/11/30 00:00 [accepted]
PHST- 2020/12/11 06:00 [pubmed]
PHST- 2021/09/07 06:00 [medline]
PHST- 2020/12/10 20:09 [entrez]
AID - S0046-8177(20)30243-4 [pii]
AID - 10.1016/j.humpath.2020.11.017 [doi]
PST - ppublish
SO  - Hum Pathol. 2021 Mar;109:37-44. doi: 10.1016/j.humpath.2020.11.017. Epub 2020 Dec 
      7.