A minority of cases of acinic cell carcinoma of the salivary glands are driven by an NR4A2 rearrangement: the diagnostic utility of the assessment of NR4A2 and NR4A3 alterations in salivary gland tumors
Jazyk angličtina Země Německo Médium print-electronic
Typ dokumentu časopisecké články
Grantová podpora
SVV 260539
Ministerstvo Školství, Mládeže a Tělovýchovy
Cooperatio Program
Univerzita Karlova v Praze
research area SURG
Univerzita Karlova v Praze
PubMed
36469101
DOI
10.1007/s00428-022-03464-8
PII: 10.1007/s00428-022-03464-8
Knihovny.cz E-zdroje
- Klíčová slova
- 9)(q13, Acinic cell carcinoma, High-grade transformation, NR4A2, NR4A3, Salivary gland, q31) translocation, t(4,
- MeSH
- acinární karcinom * diagnóza genetika metabolismus MeSH
- buněčné jádro patologie MeSH
- DNA vazebné proteiny metabolismus MeSH
- imunohistochemie MeSH
- jaderné receptory - podrodina 4, skupina A, člen 2 metabolismus MeSH
- lidé MeSH
- nádorové biomarkery analýza MeSH
- nádory slinných žláz * diagnóza genetika patologie MeSH
- receptory thyreoidních hormonů metabolismus MeSH
- slinné žlázy patologie MeSH
- steroidní receptory * genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- DNA vazebné proteiny MeSH
- jaderné receptory - podrodina 4, skupina A, člen 2 MeSH
- nádorové biomarkery MeSH
- NR4A2 protein, human MeSH Prohlížeč
- NR4A3 protein, human MeSH Prohlížeč
- receptory thyreoidních hormonů MeSH
- steroidní receptory * MeSH
Acinic cell carcinoma (AciCC) is a common salivary gland malignancy, typically composed of neoplastic acinic cells with zymogen granules. The vast majority of cases are driven by a t(4;9)(q13;q31) leading to enhancer hijacking and upregulation of the NR4A3 gene. However, a minority of cases do not display NR4A3 overexpression on immunohistochemical examination and are negative for the rearrangement involving the NR4A3 gene when tested by FISH. Such cases overexpress NR4A2, and the protein product is detectable by immunohistochemistry. In this study, we aimed to assess the utility of NR4A2 and NR4A3 immunohistochemistry in the differential diagnosis of salivary gland tumors. Eighty-five cases of classic low-grade ACiCC, as well as 36 cases with high-grade transformation (HGT) and 7 high-grade AciCC cases were included in the analysis. NR4A3 was at least focally positive in 105/128 (82%) cases. Out of the 23 cases that were immunohistochemically negative for NR4A3, 6 displayed nuclear immunopositivity with the NR4A2 antibody. The NR4A3 rearrangement was confirmed by FISH in 38/52 (73%) cases. In addition, this is the first report of an NR4A2 rearrangement being detected by FISH in 2 AciCC cases that were negative for the NR4A3 rearrangement. Our analysis confirms that the majority of AciCC, including high-grade cases and cases with HGT, are immunopositive for NR4A3, and suggests that NR4A3 immunohistochemistry is a powerful tool in the differential diagnosis of salivary gland tumors. However, its utility is limited in sub-optimally fixed samples which often display weaker and focal positivity. Our study also indicates that in a minority of cases, AciCC might be negative for NR4A3 immunostaining, because the pathogenic genetic event in these cases is instead a rearrangement involving the NR4A2 gene.
Biomedical Center Faculty of Medicine in Pilsen Charles University Pilsen Czech Republic
Bioptical Laboratory Ltd Pilsen Czech Republic
Department of Pathology Faculty of Medicine in Pilsen Charles University Pilsen Czech Republic
Department of Pathology Turku University Hospital Turku Finland
Institute of Biomedicine Pathology University of Turku Turku Finland
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