Assuntos
Biomarcadores Tumorais/análise , Carcinoma de Células Acinares/química , Proteínas de Ligação a DNA/análise , Imuno-Histoquímica , Membro 2 do Grupo A da Subfamília 4 de Receptores Nucleares/análise , Receptores de Esteroides/análise , Receptores dos Hormônios Tireóideos/análise , Neoplasias das Glândulas Salivares/química , Biomarcadores Tumorais/genética , Carcinoma de Células Acinares/genética , Carcinoma de Células Acinares/patologia , Proteínas de Ligação a DNA/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Membro 2 do Grupo A da Subfamília 4 de Receptores Nucleares/genética , Valor Preditivo dos Testes , Receptores de Esteroides/genética , Receptores dos Hormônios Tireóideos/genética , Neoplasias das Glândulas Salivares/genética , Neoplasias das Glândulas Salivares/patologia , Regulação para CimaRESUMO
Recently, we discovered the recurrent genomic rearrangement [t(4;9)(q13;q31)] enabling upregulation of the transcription factor Nuclear Receptor Subfamily 4 Group A Member 3 (NR4A3) through enhancer hijacking as the oncogenic driver event in acinic cell carcinoma (AciCC) of the salivary glands. In the current study, we evaluated the usefulness of NR4A3 immunostaining and NR4A3 fluorescence in situ hybridization (FISH) in the differential diagnosis of AciCC, comparing a total of 64 AciCCs including 17% cases with high-grade transformation, 29 secretory (mammary analog) carcinomas (MASC), and 70 other salivary gland carcinomas. Nuclear NR4A3 immunostaining was a highly specific (100%) and sensitive (98%) marker for AciCC with only 1 negative case, whereas NR4A3 FISH was less sensitive (84%). None of the MASCs or other salivary gland carcinomas displayed any nuclear NR4A3 immunostaining. The recently described HTN3-MSANTD3 gene fusion was observed in 4 of 49 (8%) evaluable AciCCs, all with nuclear NR4A3 immunostaining. In summary, NR4A3 immunostaining is a highly specific and sensitive marker for AciCC, which may be especially valuable in cases with high-grade transformation and in "zymogen granule"-poor examples within the differential diagnostic spectrum of AciCC and MASC.