J Oral Pathol Med. 2022 Sep;51(8):721-729. doi: 10.1111/jop.13341. Epub 2022 Aug 17.
ABSTRACT
BACKGROUND: Atypical/unbalanced rearrangement in salivary secretory carcinoma was observed and its incidence, patterns, and clinical significance remain unknown.
METHODS: One hundred and ninety-six cases of diagnosed secretory carcinoma were retrospectively reviewed. Fluorescence in situ hybridization for NTRK3/ETV6::NTRK3 was conducted on cases carrying the atypical ETV6 fluorescence in situ hybridization signals. Cases without ETV6::NTRK3 were selected for next-generation sequencing to reveal novel partner. Immunohistochemistry and follow-up were performed.
RESULTS: Twenty-seven cases were confirmed to carry the atypical ETV6 fluorescence in situ hybridization signal patterns. The most common type of abnormality was the duplication of ETV6 5′ end (1Y1GnR, n ≥ 2) with the incidence of 81.5% (22/27). Seventeen of 19 were identified with ETV6::NTRK3 and 2 with ETV6::RET. The immunophenotype was similar to the typical secretory carcinoma group. TrkC exhibited 68.8% sensitivity and 100% specificity for NTRK3 fusion. Microscopically, 5 out of 21 were accompanied by necrosis and 3 out of 21 showed neural invasion. Four out of 19 patients showed local relapse, 2 developed distant metastasis, and 1 died of disease. The patients with distant metastasis and even dead were both harbored ETV6::RET rearrangement. Statistical analysis revealed that there were no significant differences in disease-free survival, relapse-free survival, and distant metastasis-free survival between atypical and typical groups.
CONCLUSION: Gene rearrangement can be identified although the fluorescence in situ hybridization signals were atypical, which was instructive for secretory carcinoma diagnosis in clinical practice. The signals of partners were also always atypical which may have an impact to the efficacy of targeted drugs. There was no statistical evidence that this group possessed worse prognosis. However, secretory carcinomas with ETV6::RET have dismal prognosis than those with ETV6::NTRK3.
PMID:36087274 | DOI:10.1111/jop.13341
