Fang Wei, French Christopher A, Cameron Michael J, Han Yiding, Liu Honggang
Department of Pathology, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
Int J Surg Pathol. 2013 Apr;21(2):102-10. doi: 10.1177/1066896912451651. Epub 2012 Jul 9.
Nuclear protein in testis (NUT) midline carcinoma (NMC) is a highly malignant carcinoma originating from the midline of the body. This study investigated the clinicopathological significance of NUT rearrangements in poorly differentiated malignant tumors (PDMTs) of the upper-respiratory tract (URT) in China. The clinical and pathological features of 155 PDMTs of the URT were reviewed. Epstein-Barr virus (EBV)-encoded RNA and NUT were investigated by in situ hybridization and immunohistochemistry (IHC), respectively. NUT-positive cases were examined by fluorescence in situ hybridization (FISH) and immunohistochemical staining with a set of cytokeratins (CKs) and neuroendocrine markers. One case was observed by transmission electron microscopy. Four cases of poorly differentiated squamous cell carcinomas and sinonasal undifferentiated carcinomas were diffuse positive for NUT by IHC and also stained for antibodies to CKs and P63 but were negative for neuroendocrine markers. Only 2 of these 4 cases showed rearrangements of the NUT and BRD4 genes by FISH; both these patients died within 12 months. The remaining 2 patients showed no NUT rearrangement by FISH and did not have an aggressive clinical course. NMC is a rare, poorly differentiated carcinoma, which occurs most often in midline organs, and in this first series from China, affected the sinonasal tract of older adults and was not associated with EBV infection. Determination of NUT protein expression and gene rearrangement can allow the differentiation of NMC from other URT PDMTs. The authors suggest that molecular determination of NUT gene rearrangements should therefore represent the gold standard for NMC diagnosis.
睾丸核蛋白（NUT）中线癌（NMC）是一种起源于身体中线的高度恶性肿瘤。本研究探讨了中国上呼吸道（URT）低分化恶性肿瘤（PDMTs）中NUT重排的临床病理意义。回顾了155例URT的PDMTs的临床和病理特征。分别通过原位杂交和免疫组织化学（IHC）检测爱泼斯坦-巴尔病毒（EBV）编码RNA和NUT。对NUT阳性病例进行荧光原位杂交（FISH）以及一组细胞角蛋白（CKs）和神经内分泌标志物的免疫组织化学染色检测。通过透射电子显微镜观察了1例病例。4例低分化鳞状细胞癌和鼻窦未分化癌经免疫组化检测NUT弥漫性阳性，同时对CKs和P63抗体染色阳性，但神经内分泌标志物阴性。这4例中仅2例经FISH检测显示NUT和BRD4基因重排；这2例患者均在12个月内死亡。其余2例患者经FISH检测未显示NUT重排，临床病程也不侵袭。NMC是一种罕见的低分化癌，最常发生于中线器官，在来自中国的这首个系列病例中，累及老年成人的鼻窦，且与EBV感染无关。检测NUT蛋白表达和基因重排可将NMC与其他URT的PDMTs区分开来。作者因此建议，NUT基因重排的分子检测应成为NMC诊断的金标准。
