Acinic cell carcinoma of the salivary gland (AciCC) is a low-grade carcinoma characterized by the overexpression of the transcription factor nuclear receptor subfamily 4 group A member 3 (NR4A3). AciCC has been the subject of a few molecular research projects. This study delves into AciCC's molecular landscape to identify additional alterations and explore their clinical implications. RNA sequencing and immunohistochemical staining for markers NR4A3/NR4A2, DOG-1, S100, and mammaglobin were utilized on 41 AciCCs and 11 secretory carcinoma (SC) samples. NR4A3 was evident in 35 AciCCs, while the residual 6 were NR4A3-negative and NR4A2-positive; SC samples were consistently NR4A3-negative. A novel fusion, PON3 exon 1-LCN1 exon 5, was detected in 9/41 (21.9%) AciCCs, exhibiting a classical histologic pattern with serous cell components growing in solid sheets alongside the intercalated duct-like component. Clinical follow-up of 39 patients over a median of 59 months revealed diverse prognostic outcomes: 34 patients exhibited no disease evidence, whereas the remaining 5 experienced poorer prognosis, involving local recurrence, lymph node, and distant metastasis, and disease-associated death, 4 of which harbored the PON3::LCN1 fusion. In addition, the HTN3::MSANTD3 fusion was recurrently identified in 7/41 AciCC cases. SC patients lacked both fusions. Immunohistochemistry uncovered differential expression of DOG-1, S100, and mammaglobin across samples, providing nuanced insights into their roles in AciCC. This study accentuates PON3::LCN1 and HTN3::MSANTD3 fusions as recurrent molecular events in AciCC, offering potential diagnostic and prognostic utility and propelling further research into targeted therapeutic strategies.

中文翻译：

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PON3::LCN1 和 HTN3::MSANTD3 基因融合与唾液腺腺泡细胞癌中 NR4A3/NR4A2 的表达。


唾液腺腺泡细胞癌 (AciCC) 是一种低级别癌，其特征是转录因子核受体亚家族 4 A 组成员 3 (NR4A3) 过度表达。 AciCC 一直是一些分子研究项目的主题。这项研究深入研究了 AciCC 的分子结构，以确定其他改变并探索其临床意义。对 41 个 AciCC 和 11 个分泌性癌 (SC) 样本进行了 RNA 测序和标记物 NR4A3/NR4A2、DOG-1、S100 和乳房珠蛋白的免疫组织化学染色。 35 个 AciCC 中 NR4A3 明显，其余 6 个为 NR4A3 阴性和 NR4A2 阳性； SC 样本始终为 NR4A3 阴性。在 9/41 (21.9%) AciCC 中检测到一种新的融合物 PON3 外显子 1-LCN1 外显子 5，表现出经典的组织学模式，浆液细胞成分沿着嵌入的导管状成分生长在实心片中。对 39 名患者的临床随访中位时间为 59 个月，结果显示不同的预后结果：34 名患者没有表现出疾病证据，而其余 5 名患者的预后较差，包括局部复发、淋巴结转移、远处转移以及疾病相关死亡。其中 4 个包含 PON3::LCN1 融合。此外，在 7/41 AciCC 病例中反复鉴定出 HTN3::MSANTD3 融合。 SC 患者缺乏两种融合。免疫组织化学揭示了样本中 DOG-1、S100 和乳房珠蛋白的差异表达，为了解它们在 AciCC 中的作用提供了细致入微的见解。这项研究强调 PON3::LCN1 和 HTN3::MSANTD3 融合是 AciCC 中反复发生的分子事件，提供潜在的诊断和预后实用性，并推动对靶向治疗策略的进一步研究。