• MeSH
• dospělí MeSH
• gen SMARCB1 genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikro RNA biosyntéza   MeSH
• nádorové biomarkery MeSH
• nádory vedlejších dutin nosních genetika   patologie   MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• gen SMARCB1 MeSH
• mikro RNA MeSH
• nádorové biomarkery MeSH
• SMARCB1 protein, human MeSH Prohlížeč

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.

• Klíčová slova
• biomarker, head and neck cancer, miR-21, microRNA, sinonasal carcinoma,
• MeSH
• analýza přežití MeSH
• analýza rozptylu MeSH
• imunohistochemie MeSH
• jehlová biopsie MeSH
• Kaplanův-Meierův odhad MeSH
• kvantitativní polymerázová řetězová reakce metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikro RNA genetika   MeSH
• nádorové biomarkery genetika   MeSH
• nádory vedlejších dutin nosních genetika   mortalita   patologie   chirurgie   MeSH
• neparametrická statistika MeSH
• prognóza MeSH
• regulace genové exprese u nádorů * MeSH
• reprodukovatelnost výsledků MeSH
• senioři MeSH
• spinocelulární karcinom genetika   mortalita   patologie   chirurgie   MeSH
• stanovení celkové genové exprese MeSH
• studie případů a kontrol MeSH
• upregulace MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• mikro RNA MeSH
• MIRN21 microRNA, human MeSH Prohlížeč
• nádorové biomarkery MeSH

The aim of the study was detailed clinicopathological investigation of SMARCB1/INI1-deficient sinonasal carcinomas, including molecular genetic analysis of mutational status and DNA methylation of selected protooncogenes and tumor suppressor genes by means of next generation sequencing (NGS) and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA). A total of 4/56 (7%) cases of SMARCB1/INI1-deficient carcinomas were detected among 56 sinonasal carcinomas diagnosed over a 19year period using immunohistochemical screening. The series comprised 3 males and 1 female, aged 27-76 years (median 64 years). All tumors arose in the nasal cavity. Three neoplasms were diagnosed in advanced stage pT4. During the follow-up period (range 14-111 months (median 72 months)), three tumors recurred locally, but none of the patients developed regional or distant metastases. Ultimately, two patients died due to the tumor. Microscopically, all tumors consisted of infiltrating nests of polygonal basaloid cells with a variable component of rhabdoid cells with eosinophilic cytoplasm. Immunohistochemically, there was almost diffuse expression of cytokeratins (CK), p16, p40 and p63 in all cases, while expression of CK5/6, CK7 and vimentin was only focal or absent. The detection of NUT gave negative results. In three cases, the absence of SMARCB1/INI1 expression was due to deletion of SMARCB1/INI1 gene. Methylation of SMARCB1/INI1 gene was not found. One tumor harbored HPV18 E6/E7 mRNA. All 12 genes (BRAF, BRCA1, BRCA2, KIT, EGFR, KRAS, NRAS, PDGFRA, PIK3CA, PTEN, RET, and ROS1) tested for mutations using NGS were wild-type. Regarding DNA methylation, all four SMARCB1/INI1-deficient tumors showed methylation of RASSF1 gene by means of MS-MLPA. There was a statistically significant difference in RASSF1 gene methylation between SMARCB1/INI1-deficient and SMARCB1/INI1-positive tumors (p=0.0095). All other examined genes (ATM, BRCA1, BRCA2, CADM1, CASP8, CD44, CDKN1B, CDKN2A, CDKN2B, CHFR, DAPK1, ESR1, FHIT, GSTP1, HIC1, KLLN, MLH1a, MLH1b, RARB, and VLH) were unmethylated. In summary, we described four cases of SMARCB1/INI1-deficient sinonasal carcinoma with detailed clinicopathological data indicating that these tumors can be regarded as a distinct entity with aggressive behaviour. For the first time, we performed analysis of DNA methylation in SMARCB1/INI1-deficient sinonasal carcinomas, reporting on significantly higher methylation of RASSF1 gene in this neoplasm.

• Klíčová slova
• DNA methylation, RASSF1, Rhabdoid, SMARCB1/INI1, Sinonasal tract, Squamous cell carcinoma,
• MeSH
• dospělí MeSH
• gen SMARCB1 genetika   metabolismus   MeSH
• imunohistochemie MeSH
• karcinom genetika   metabolismus   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metylace DNA * MeSH
• nádorové biomarkery genetika   metabolismus   MeSH
• nádorové supresorové proteiny genetika   metabolismus   MeSH
• nádory sinu maxillaris genetika   metabolismus   patologie   MeSH
• senioři MeSH
• staging nádorů MeSH
• vysoce účinné nukleotidové sekvenování MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• gen SMARCB1 MeSH
• nádorové biomarkery MeSH
• nádorové supresorové proteiny MeSH
• RASSF1 protein, human MeSH Prohlížeč

Development of targeted cancer therapy is accompanied by a search for markers allowing prediction of response to the particular treatment. Recently, the interest is focused, among other neoplasms, also on the therapy of ovarian cancer using new inhibitors of poly (ADP-ribose) polymerase (PARP) proteins, nuclear enzymes involved in the repair of single-stranded DNA breaks. The greatest benefit from the administration of PARP inhibitors have patients with a deleterious or potentially deleterious germ-line or somatic mutation of BRCA1 or BRCA2, two genes responsible for repair of double stranded DNA breaks. There has been described a wide spectrum of mutations of BRCA 1/2, from point substitutions to large deletions, including sometimes even several exons of the gene.Unlike the testing of germ-line mutations provided for many years by the medical geneticists, somatic mutations in the tumor tissue have not been routinely tested so far. Detection of BRCA1/2 mutations in the tumor is significantly different from testing of germ-line mutations. In comparison with the analysis of DNA isolated from blood samples, testing of DNA isolated from the FFPE tissue encounters challenges based on heterogeneous representation of tumor cells in the tissue samples, on the presence of multiple neoplastic clones and on the infiltration of tissue by the non-neoplastic elements, as well as difficulties caused by variable proportion of apoptotic and necrotic cells deteriorating the overall quality of isolated DNA.Regarding the testing methods, NGS appears to be the optimal choice because of its complexity, speed of implementation into routine diagnostics as well as sensitivity for detection of a BRCA 1/2 mutations. When introduced into everyday laboratory practice, the functioning quality control system is of utmost importance. Provided there is a high probability of detection of the so far unreported variations in BRCA 1/2 genes, an introduction of a shared database of somatic variants diagnosed in the Czech Republic would be of enormous benefit.

• Klíčová slova
• BRCA1 - BRCA2 - ovarian cancer - FFPE - DNA sequencing - next generation sequencing - NGS.,
• MeSH
• lidé MeSH
• mutační analýza DNA metody   MeSH
• nádory prsu genetika   patologie   MeSH
• nádory vaječníků genetika   patologie   MeSH
• protein BRCA1 genetika   MeSH
• protein BRCA2 genetika   MeSH
• zárodečné mutace * MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• BRCA1 protein, human MeSH Prohlížeč
• BRCA2 protein, human MeSH Prohlížeč
• protein BRCA1 MeSH
• protein BRCA2 MeSH

The aim of the study was to investigate prevalence of high-risk human papillomavirus (HR-HPV) infection in sinonasal carcinomas by immunohistochemistry, in situ hybridization, and polymerase chain reaction, detecting p16(INK4a) protein (p16) expression and presence of both HPV DNA and HPV E6/E7 messenger RNA (mRNA). The study comprised 47 males and 26 females, aged 23-83 years (median 62 years), mostly (67 %) with a squamous cell carcinoma (SCC). Of the tumors, 53 % arose in the nasal cavity, 42 % in the maxillary sinus, and 5 % in the ethmoid complex. The follow-up period ranged 1-241 months (median 19 months). HPV16, HPV18, or HPV35 were detected in 18/73 (25 %) tumors, 17 SCCs, and 1 small cell neuroendocrine carcinoma. There was a strong correlation between results of HPV detection methods and p16 expression (p < 0.005). HPV-positive SCCs occurred more frequently in smokers (p = 0.04) and were more frequently p16-positive (p < 0.0001) and nonkeratinizing (p = 0.02), the latter occurring more commonly in nasal cavity (p = 0.025). Median survival for HPV-positive SCC patients was 30 months, while for HPV-negative SCC patients was 14 months (p = 0.23). In summary, we confirm that HR-HPV is actively involved in the etiopathogenesis of a significant subset of sinonasal SCCs. p16 may be used as a reliable surrogate marker for determination of HPV status also in sinonasal SCCs. Although we observed a trend toward better overall survival in HPV-positive SCCs, the prognostic impact of HPV status in sinonasal carcinomas needs to be elucidated by further studies.

• Klíčová slova
• Human papillomavirus (HPV), Nonkeratinizing, RNA, Sinonasal carcinoma, Squamous cell carcinoma, p16 protein,
• MeSH
• dlaždicobuněčné karcinomy hlavy a krku MeSH
• DNA virů analýza   MeSH
• dospělí MeSH
• genetická transkripce MeSH
• imunohistochemie MeSH
• inhibitor p16 cyklin-dependentní kinasy MeSH
• lidé středního věku MeSH
• lidé MeSH
• messenger RNA analýza   MeSH
• nádorové proteiny analýza   MeSH
• nádory hlavy a krku mortalita   patologie   virologie   MeSH
• nádory vedlejších dutin nosních mortalita   patologie   virologie   MeSH
• onkogenní proteiny virové genetika   MeSH
• Papillomaviridae izolace a purifikace   MeSH
• Papillomavirus E7 - proteiny genetika   MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• represorové proteiny genetika   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• spinocelulární karcinom mortalita   patologie   virologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• CDKN2A protein, human MeSH Prohlížeč
• DNA virů MeSH
• E6 protein, Human papillomavirus type 16 MeSH Prohlížeč
• inhibitor p16 cyklin-dependentní kinasy MeSH
• messenger RNA MeSH
• nádorové proteiny MeSH
• oncogene protein E7, Human papillomavirus type 16 MeSH Prohlížeč
• onkogenní proteiny virové MeSH
• Papillomavirus E7 - proteiny MeSH
• represorové proteiny MeSH