Sinonasal cancers represent a highly heterogeneous group of head and neck cancers, for which etiological and prognostic significance of high-risk human papillomavirus (HPV) infections has not yet been conclusively established. We investigated the presence of transcriptionally-active high-risk HPV in a series of 34 sinonasal squamous cell cancer (SNSCC) cases and evaluated the effect of transcriptionally-active HPV on the overall survival. In addition, we performed a meta-analysis of previously published studies, including this study, to summarize the prevalence of HPV positivity across histological subtypes of SNSCC. The presence of transcriptionally-active HPV was detected by HPV mRNA using the polymerase chain reaction (PCR) or in situ hybridization (ISH). p16 expression was evaluated as a surrogate marker for transcriptionally-active HPV infection by immunohistochemistry (IHC), the presence of high-risk HPV DNA was tested by PCR and the HPV genotypes were determined by sequencing of PCR amplicons. Transcriptionally-active HPV infections were found in ~25% of the SNSCC cases. The role of HPV infection in keratinizing SNSCC may be higher than previously reported (~32% in our study vs. ~0-6.3% in all other studies). Patients with transcriptionally-active HPV-positive SNSCCs were more likely to be diagnosed at earlier stages (p<0.05) and displayed better mean overall survival, although the difference between HPV-positive and HPV-negative groups was not statistically significant. In contrast to other non-oropharyngeal squamous cell carcinomas (non-OPSCCs) of the head and neck, in SNSCCs, p16/IHC and p16/IHC+HPV DNA displayed high specificity as surrogate markers of transcriptionally-active HPV infections. However, p16/IHC may have significantly lower sensitivity as a surrogate marker of transcriptionally-active HPV in SNSCCs compared to OPSCCs. Furthermore, in our group of SNSCCs, all cases positive for high-risk HPV DNA by PCR were also transcriptionally-active (causative) infections with positive HPV mRNA by ISH. Our results imply a possible different role of HPV-mediated carcinogenesis of squamous cell epithelium in oropharyngeal and sinonasal sites with the latter displaying a lower proportion of causative HPV infections; nevertheless, most cases positive for high-risk HPV DNA, p16/IHC or combination thereof were also found positive for transcriptionally-active HPV. The prognostic significance of HPV status in SNSCCs remains inconclusive and future studies should investigate the presence of transcriptionally-active HPV by direct HPV testing.
- MeSH
- Alphapapillomavirus * MeSH
- DNA virů genetika MeSH
- imunohistochemie MeSH
- infekce papilomavirem komplikace MeSH
- inhibitor p16 cyklin-dependentní kinasy MeSH
- lidé MeSH
- nádorové biomarkery MeSH
- nádory nosu virologie MeSH
- paranazální dutiny patologie MeSH
- RNA virová MeSH
- spinocelulární karcinom virologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
Aim: We examined associations of eight SNPs in/near seven candidate genes with glycemic response to 6 month treatment with DPP4 inhibitors. Patients & methods: 206 patients with type 2 diabetes (116 men and 90 women) were treated with sitagliptin or vildagliptin (both 100 mg/day) in combination with metformin or metformin/sulphonylurea over 6 months, and the reduction in glycated hemoglobin (HbA1c) was measured. Results: Rs6923761 in GLP1R was significantly associated with a reduction in HbA1c (adjusted p = 0.006). Homozygotes for the minor A allele had smaller reduction in HbA1c by 0.4% (4 mmol/mol) than the G allele carriers (p = 0.016). Conclusion: The missense variant rs6923761 in the GLP1R gene was associated with a smaller glycemic response to 6 month gliptin therapy in diabetic patients of central European origin.
Duodenal biopsy is an essential component in the diagnosis of celiac disease (CD). Although the classical findings of increased number of intraepithelial lymphocytes, crypt hyperplasia and villous atrophy are very characteristic, the diagnosis cannot be achieved on the basis of histopathology alone, as there are many entities that can mimic CD and a close collaboration of a pathologist and a clinician specialist is needed. In a patient with suspected CD, pathologist should describe essential histopathological findings and offer differential diagnosis when appropriate. The most important recent changes in the diagnostic criteria for CD include lower numbers of intraepithelial lymphocytes that are considered to be normal and recommendation to perform biopsies from the proximal part of the duodenum in addition to the distal duodenal biopsies.
- Klíčová slova
- počet intraepiteliálních lymfocytů (IEL),
- MeSH
- biopsie * MeSH
- celiakie * diagnóza patologie prevence a kontrola MeSH
- diferenciální diagnóza * MeSH
- duodenum * MeSH
- histologie srovnávací * MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- Geografické názvy
- Česká republika MeSH
- Slovenská republika MeSH
