cyclin-d1 and Sinusitis

The sinonasal tract is a common extranodal site for Rosai-Dorfman disease (RDD). Recently, histiocytes with features of RDD were identified in the clinical setting of chronic sinusitis. This study evaluates whether this phenomenon should be considered part of the RDD spectrum or classified separately as RDD-like histiocytes.. We prospectively collected 13 cases showing histological features of RDD in chronic sinusitis patients and identified 14 with similar findings (3.5%) via retrospective review of 403 sinus contents over 2 years. All 27 cases displayed nodular aggregates of eosinophilic histiocytes with intermixed lymphoplasmacytic inflammation, prominent eosinophils and emperipolesis. The histiocytes were positive for S100 protein and cyclin D1 and negative for CD1a and CD207. All patients presented with severe chronic sinusitis without tumour formation or systemic symptoms. Twelve patients with follow-up (55%) required repeat sinus surgery compared with just 43 other sinusitis patients evaluated (11%); features of RDD were present in their additional specimens. Two cases that underwent targeted next-generation sequencing (20%) had oncogenic mutations in NF1 and KEAP1.. Overall, these findings confirm diagnostic histological and immunohistochemical features of RDD in a subset of chronic sinusitis specimens. While patients uniformly lack systemic involvement or tumefactive growth, they have a high risk of recurrent sinus disease. Although the relatively subtle nature of the findings raises consideration of separate classification, the presence of occasional oncogenic mutations and evidence of consistent MAPK/ERK pathway activation via cyclin D1 positivity suggests that this phenomenon represents a unique limited manifestation of RDD.

Topics: Cyclin D1; Histiocytosis, Sinus; Humans; Kelch-Like ECH-Associated Protein 1; NF-E2-Related Factor 2; Sinusitis

Epithelial to mesenchymal transition (EMT) is associated with the pathophysiology of chronic rhinosinusitis with nasal polyp (CRSwNP). Wnt signaling is causative for EMT, whereas the mechanism in CRSwNP is not fully understood.. We sought to evaluate the role of Wnt signaling in EMT of CRSwNP using a murine nasal polyp (NP) model and human tissues.. Inflammatory markers and EMT-related molecules were evaluated in NP models using adenomatosis polyposis coli (Apc). Apc. Wnt signaling may contribute to the pathogenesis of NPs through EMT. Therefore, inhibition of Wnt signaling may be a potential therapeutic strategy for patients with CRSwNP.

Topics: Actins; Adenomatous Polyposis Coli Protein; Animals; beta Catenin; Biomarkers; Cadherins; Cyclin D1; Disease Models, Animal; Epithelial-Mesenchymal Transition; Humans; Indocyanine Green; Mice; Nasal Polyps; Rhinitis; Sinusitis; Twist-Related Protein 1; Up-Regulation; Wnt Signaling Pathway

The pathogenesis of human chronic rhinosinusitis (CRS) remains controversial. Recent evidence has suggested that caveolin-1 (Cav-1) is a 22 kDa scaffolding protein and plays a pivotal role in host defense against infections and tumour suppression by reducing production of cyclin D1 and endothelial nitric oxide-synthase (eNOS). However, little is known about their roles in CRS. Therefore, we aimed to investigate the expression and role of Cav-1 in CRS. Cav-1 protein expression were investigated by immunohistochemistry method and mRNA expression of Cav-1, cyclin D1 and eNOS were assessed by real-time polymerase chain reaction in CRS and control subjects. Moreover, the effects of various stimulators with different concentrations and time on Cav-1 were evaluated on nasal explant culture. The results showed that weaker expression of Cav-1 protein and mRNA were observed in CRS, especially in CRS with nasal polyps (CRSwNP), stronger mRNA expression of cyclin D1 and eNOS were observed in CRS and Cav-1 expression was negatively related to cyclin D1 and eNOS expression, respectively. Cav-1 mRNA was augmented by IFN-γ, but supressed by IL-4 and IL-1β. In conclusion, the expression of Cav-1 was downregulated in CRS and the role of Cav-1 was impaired in CRS, especially in CRSwNP, leading to the attenuation of inhibition effect on cyclin D1 and eNOS and resulted in the overexpression of cyclin D1 and eNOS. IFN-γ may be essential for Cav-1 gene expression.

Topics: Adolescent; Adult; Aged; Case-Control Studies; Caveolin 1; Cyclin D1; Down-Regulation; Female; Humans; Immunohistochemistry; Interferon-gamma; Interleukin-1beta; Interleukin-4; Male; Middle Aged; Nasal Polyps; Nitric Oxide Synthase; Real-Time Polymerase Chain Reaction; Rhinitis; RNA, Messenger; Sinusitis; Young Adult