Pan-tropomyosin receptor kinase immunoreactivity, ETV6-NTRK3 fusion subtypes, and RET rearrangement in salivary secretory carcinoma

Hidetaka Yamamoto, Yui Nozaki, Azusa Sugii, Kenichi Taguchi, Takahiro Hongo, Rina Jiromaru, Masanobu Sato, Takafumi Nakano, Kazuki Hashimoto, Minako Fujiwara, Yoshinao Oda

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)37-44
Number of pages8
JournalHuman Pathology
Volume109
DOIs
Publication statusPublished - Mar 2021

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

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