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Pan-tropomyosin receptor kinase immunoreactivity, ETV6-NTRK3 fusion subtypes, and RET rearrangement in salivary secretory carcinoma.
- Source :
-
Human pathology [Hum Pathol] 2021 Mar; Vol. 109, pp. 37-44. Date of Electronic Publication: 2020 Dec 07. - Publication Year :
- 2021
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Abstract
- 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.<br /> (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Subjects :
- Adolescent
Adult
Aged
Biomarkers, Tumor analysis
Breast Neoplasms genetics
Breast Neoplasms metabolism
Carcinoma genetics
Carcinoma metabolism
Child
Female
Gene Rearrangement genetics
Humans
Immunohistochemistry methods
Middle Aged
Oncogene Proteins, Fusion genetics
Oncogene Proteins, Fusion metabolism
Protein-Tyrosine Kinases genetics
Proto-Oncogene Proteins genetics
Proto-Oncogene Proteins c-ret genetics
Proto-Oncogene Proteins c-ret metabolism
Receptor Protein-Tyrosine Kinases genetics
Salivary Gland Neoplasms genetics
Salivary Gland Neoplasms immunology
Salivary Gland Neoplasms pathology
Tropomyosin genetics
Young Adult
Breast Neoplasms immunology
Carcinoma immunology
Oncogene Proteins, Fusion immunology
Proto-Oncogene Proteins c-ret immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1532-8392
- Volume :
- 109
- Database :
- MEDLINE
- Journal :
- Human pathology
- Publication Type :
- Academic Journal
- Accession number :
- 33301751
- Full Text :
- https://doi.org/10.1016/j.humpath.2020.11.017