Department of Medical Oncology, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China.
Department of Pathology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Cancer Med. 2021 Sep;10(17):5757-5764. doi: 10.1002/cam4.4096. Epub 2021 Aug 19.
Pulmonary nuclear protein of the testis (NUT) midline carcinoma (NMC) is a aggressive cancer with t (15, 19) translocation. Here we present the clinicopathological characteristics and molecular genetics alterations of primary pulmonary NMC.
Fluorescence in situ hybridization (FISH) assay was performed to evaluate NUT translocation. Next generation sequencing (NGS) was performed to investigate genomic landscape. A panel of 289 lung cancer tissues with undifferentiation was retrospectively screened for NUT expression by immunohistochemical (IHC) assay.
Overall, 2136 lung cancer samples were reviewed. We consecutively identified 12 cases of primary pulmonary NMC. Computed tomography revealed centrally located bulky lung mass with ipsilateral mediastinal lymph node and pleural involvements. Tumor cells presented diffuse poor differentiation and focal squamous differentiation with positive NUT expression. NUT rearrangement was confirmed by FISH assay. Ten NMC samples were investigated by NGS. The most common alterations identified were P53, PIK3CA, AUTS2, ITIH2, and CDKL5 genes. Pulmonary NMC exhibited increased activity of PI3K/AKT pathway. In the screening study, BRD4-NUT rearrangement was identified in two cases.
NUT rearrangement remains the gold standard in the diagnosis of pulmonary NMC. PI3K inhibition is a potential targeted therapy for pulmonary NMC.
睾丸核蛋白（NUT）中线癌（NMC）是一种具有 t（15,19）易位的侵袭性癌症。在此，我们介绍了原发性肺 NMC 的临床病理特征和分子遗传学改变。
采用荧光原位杂交（FISH）检测 NUT 易位。进行下一代测序（NGS）以研究基因组景观。通过免疫组织化学（IHC）检测对 289 例未分化的肺癌组织进行了 NUT 表达的回顾性筛选。
总共回顾了 2136 例肺癌样本。我们连续确定了 12 例原发性肺 NMC。计算机断层扫描显示中央性大肺肿块伴同侧纵隔淋巴结和胸膜受累。肿瘤细胞呈弥漫性低分化和局灶性鳞状分化，NUT 表达阳性。FISH 检测证实 NUT 重排。对 10 例 NMC 样本进行了 NGS 研究。最常见的改变包括 P53、PIK3CA、AUTS2、ITIH2 和 CDKL5 基因。肺 NMC 表现出 PI3K/AKT 通路活性增加。在筛选研究中，两个病例中发现了 BRD4-NUT 重排。
NUT 重排仍然是诊断肺 NMC 的金标准。PI3K 抑制是肺 NMC 的一种潜在靶向治疗方法。
