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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.

Background: Tumors occurring in the sinonasal area are characterized by unfavorable outcome due to difficult diagnosis, treatment, and prognosis of the disease corresponding with the anatomic complexity of the area., Methods: We used quantitative real-time polymerase chain reaction (PCR) to compare relative expression of miR-21, miR-141, and miR-200c in 70 formalin-fixed, paraffin-embedded samples of sinonasal carcinoma tissue (majority of squamous cell carcinoma [SCC] samples) with 17 control samples of sinonasal tissue., Results: Our data showed significant upregulation of miR-21 in sinonasal cancer tissue. Expression levels of miR-141 and miR-200c were below detectable levels in both sinonasal cancer samples and healthy tissue. Kaplan-Meier analysis with log-rank survival showed that patients with SCC with high expression of miR-21 (highest quartile) had impaired survival close to reaching statistical significance (P = .0630)., Conclusion: Our results suggest that miR-21 upregulation is involved in tumorigenesis of sinonasal carcinoma and that it is associated with poor prognosis. Thus, miR-21 could be used as a valuable prognostic biomarker., (© 2017 Wiley Periodicals, Inc.)