Neoplasma. 2018;65(1):113-123. doi: 10.4149/neo_2018_161122N581.
The aim of this study was a detailed clinicopathological investigation of sinonasal NUT midline carcinoma (NMC), including analysis of DNA methylation and microRNA (miRNA) expression. Three (5%) cases of NMC were detected among 56 sinonasal carcinomas using immunohistochemical screening and confirmed by fluorescence in situ hybridization. The series comprised 2 males and 1 female, aged 46, 60, and 65 years. Two tumors arose in the nasal cavity and one in the maxillary sinus. The neoplasms were staged pT1, pT3, and pT4a (all cN0M0). All patients were treated by radical resection with adjuvant radiotherapy. Two patients died 3 and 8 months after operation, but one patient (pT1 stage; R0 resection) experienced no evidence of disease at 108 months. Microscopically, all tumors consisted of infiltrating nests of polygonal cells with vesicular nuclei, prominent nucleoli and basophilic cytoplasm. Abrupt keratinization was present in only one case. Immunohistochemically, there was a diffuse expression of cytokeratin (CK) cocktail, CK7, p40, p63, and SMARCB1/INI1. All NMCs tested negative for EBV and HPV infection. Two NMCs showed methylation of RASSF1 gene. All other genes (APC, ATM, BRCA1, BRCA2, CADM1, CASP8, CD44, CDH13, CDKN1B, CDKN2A, CDKN2B, CHFR, DAPK1, ESR1, FHIT, GSTP1, HIC1, KLLN, MLH1a, MLH1b, RARB, TIMP3, and VHL) were unmethylated. All NMCs showed upregulation of miR-9 and downregulation of miR-99a and miR-145 and two cases featured also upregulation of miR-21, miR-143, and miR-484. In summary, we described three cases of sinonasal NMCs with novel findings on DNA methylation and miRNA expression, which might be important for new therapeutic strategies in the future.
本研究旨在对鼻窦神经内分泌尿路上皮癌（NMC）进行详细的临床病理研究，包括 DNA 甲基化和 microRNA（miRNA）表达分析。通过免疫组织化学筛选，在 56 例鼻窦癌中发现了 3 例（5%） NMC，并通过荧光原位杂交技术得到了证实。该系列包括 2 名男性和 1 名女性，年龄分别为 46、60 和 65 岁。2 例肿瘤发生于鼻腔，1 例发生于上颌窦。肿瘤分期分别为 pT1、pT3 和 pT4a（均为 cN0M0）。所有患者均接受根治性切除术联合辅助放疗。2 例患者术后 3 个月和 8 个月死亡，但 1 例（pT1 期；RO 切除）在 108 个月时未发现疾病证据。显微镜下，所有肿瘤均由多边形细胞浸润巢组成，细胞核呈泡状，核仁明显，细胞质嗜碱性。仅 1 例可见突然角化。免疫组织化学检查显示 CK 鸡尾酒、CK7、p40、p63 和 SMARCB1/INI1 弥漫性表达。所有 NMC 均检测 EBV 和 HPV 感染阴性。2 例 NMC 显示 RASSF1 基因甲基化。所有其他基因（APC、ATM、BRCA1、BRCA2、CADM1、CASP8、CD44、CDH13、CDKN1B、CDKN2A、CDKN2B、CHFR、DAPK1、ESR1、FHIT、GSTP1、HIC1、KLLN、MLH1a、MLH1b、RARB、TIMP3 和 VHL）均未甲基化。所有 NMC 均显示 miR-9 上调，miR-99a 和 miR-145 下调，2 例还显示 miR-21、miR-143 和 miR-484 上调。总之，我们描述了 3 例鼻窦 NMC 病例，发现了 DNA 甲基化和 miRNA 表达的新发现，这可能对未来的新治疗策略很重要。
