The central odontogenic fibroma (COF) is a rare benign odontogenic mesenchymal tumor of jaw bones. The World Health Organization (WHO) recognizes two variants of COF namely: 1) Epithelial-rich type (WHO) and 2) epithelial-poor type (simple type). Rare variants like ossifying COF, COF associated with giant cell lesions, and amyloid have been documented. This article presents a case of an epithelial-rich variant of COF in a 24-year-old female. It presented as a bony swelling of the maxilla and appeared as a mixed lesion in radiographs. Histopathology showed a highly cellular fibrous connective tissue stroma with plump fibroblasts and long strands of odontogenic epithelium exhibiting mild eosinophilic to clear cytoplasm. Numerous cementum-like hematoxyphilic calcifications of various sizes akin to dentin or acellular cementum were observed. We believe that clinical and radiographic features of this case may add valuable knowledge to the already existing literature.

Aggresomes are transient microtubule-dependent inclusion bodies that sequester misfolded proteins and are ultimately removed by autophagy. Here we report the generation of a choroid plexus carcinoma cell line; Children’s Cancer Hospital Egypt (CCHE)-45, which is characterized by the constitutive formation of aggresomes. When examining the autophagy pathway as the main route for aggresomes clearance, CCHE-45 cells displayed increased autophagy flux mediated by MAP1LC3B. MAP1LC3A-Variant1 gene expression was silenced by promoter methylation. Restoring MAP1LC3A-Variant1 expression resulted in the formation of MAP1LC3A positive autophagosmes and the disruption of the aggresomes' vimentin cage independent of MAP1LC3B positive autophagosomes. Our data supports the notion that basal quality control autophagy and vimentin cage clearance in CCHE-45 are mediated by MAP1LC3A. Hence we propose that absence of MAP1LC3A disrupts the autophagic pathway and leads to the failure of aggresome vimentin cage degradation. Consequently, this could represent a targetable pathway in autophagy-dependent cancers.

Background:Oral squamous cell carcinoma (OSCC) is the most common malignancy of the oral mucosa. Stromal myofibroblasts play an important role in tumor invasion and metastasis, due to its ability to modify the extracellular matrix. The purpose of this study was to evaluate and compare the presence of myofibroblasts in normal mucosa, early invasive carcinoma and different grades of OSCC.Materials and Methods:The study included the archival tissues of 18 OSCC of well, moderate and poorly differentiated grades, three early invasive carcinomas and five normal mucosa. Myofibroblasts were identified by immunohistochemical detection of h1 calponin.Results:The percentage and intensity of h1 calponin were examined and positive immunostaining was observed in the myofibroblasts of all SCCs and early invasive carcinomas; however, these cells did not stain in the normal epithelium specimens. The presence of myofibroblasts was significantly higher in invasive pattern of OSCCs compared to normal mucosa cases (P < 0.070). A significant difference was not observed between the different grades of OSCC (P ≤ 0.812).Conclusion:These findings show the presence of myofibroblasts in OSCC but not in normal mucosa, suggesting that the genetically altered epithelium (carcinomatous epithelium) may have an inductive effect on the adjacent stroma to produce myofibroblasts. Also transdifferentiation of myofibroblasts is induced somewhere in the invasive stage of SCC irrespective of the epithelial cell differentiation.

Different genetic and environmental factors are implicated in type I diabetes (T1DM) pathogenesis. About 50% of the genetic susceptibility for T1DM is related to human leukocyte antigen (HLA) genes. Other non-HLA genes have variable roles in the destruction of pancreatic β cells. A highly variable gene called endoplasmic reticulum associated with antigen processing gene 1(ERAP1) shares in activating autoreactive CD8+ T lymphocytes, peptide trimming, and subsequent pancreatic β cells destruction. Local production of inflammatory cytokines within the cells of islets of Langerhans is linked to T1DM progression. Different viral and autoimmune disorders have been linked to genetic variations in type III interferon (IFNλs). This study aimed to determine genetic polymorphisms of interferon lambda 4 (IFNλ4rs 73555604) and endoplasmic reticulum aminopeptidases 1 (ERAP1 rs26618) in Egyptian patients with T1DM. The study recruited 120 patients with T1DM from Kafrelsheikh University Hospital and 100 normal controls who were age and sex matched with the patients’ group. Single-nucleotide polymorphism (SNP) genotyping of ERAP1(rs26618) and IFN-λ-4(rs73555604) was performed using real-time polymerase chain reaction. Patients with CC genotype were less likely to develop T1DM than those with TC and TT genotypes for both genes. In addition, T allele frequency in comparison to C allele frequency was significantly increased in T1DM patients when compared to control group (p<0.001). There were positive correlations between studied SNPs for both genes, fasting and postprandial blood glucose levels which suggest the association of these genes with T1DM occurrence. We concluded that the studied SNPs of ERAP1gene (rs26618) and IFNλ-4 gene(rs73555604) may be associated with T1DM development. In addition, T alleles for both genes could be considered risk alleles while C alleles would be regarded as a protective allele. Patients with TC and TT genotypes would be at a higher risk for T1DM than those carrying CC genotype.

Our long-term goal is to define and characterize the mechanisms underlying aggresome formation in choroid plexus carcinoma a rare pediatric tumor. Protein misfolding is inevitable, 30% of newly synthesized polypeptides can end up misfolded, such proteins are either refolded or eliminated by cellular quality control pathways which include the ubquitin proteosome system and autophagy. In recent years, protein misfolding has been implicated in the pathophysiology of many diseases such as diabetes, neurological disorders and cancer. Studies from our laboratory have shown that choroid plexus carcinoma tumors are characterized by the formation of aggresomes at the microtubules organizing centers (MTOC) in FFPE tumor tissues. This was further conformed by the development of choroid plexus carcinoma cell line (CPC-45) which was characterized by the constitutive formation of aggresomes at MTOC. When examining the soluble and insoluble fractions, vimentin was only identified in the insoluble fraction. These results were further confirmed using electron microscopy. Aggresome formation implies presence of toxic protein over load and/or defective autophagy. CPC-45 cells displayed normal LC3B (an indicator of autophagosome) expression and regulation upon nutrient deprivation. To further monitor autophagy, CPC-45 and SHY-5Y cells were infected with the dual Tandem Sensor RFP-GFP-LC3B to label autophagosome and its maturation to autolysosome. While SHY-5Y displayed both green and red fluorescence upon infection, CPC-45 was only positive after serum starvation thus confirming the targeting of aggresomes by LC3B mediated autophagy. Recently, the LC3B paralog LC3AV1 was found to be silenced by DNA methylation in several cancer cell lines and reported as major player in autophagy and as a potential tumor suppressor. To further explore the role of LC3A in aggresome formation, CPC-45 cells were transfected with either GFP empty vector or LC3AV1-GFP construct. Only LC3A-GFP transfected cells were positive for aggresome formation while in GFP transfected we did not observe any signal. Consistent with previous reports that over expression of GFP results in protein accumulation at the aggresomes. Our results suggest that LC3A is the mediator of the basal quality control function of autophagy which is different from the stress induced autophagy mediated by LC3B. Based on our findings, we propose that perturbation in the autophagic pathway due lack of LC3Av1 expression lead to a failure in the aggresome degradation process and hence provide an advantage to tumor cells to overcome protein misfold overload thus contributing to the tumorigenicity of the disease. Citation Format: Heba Samaha, Marwa Nassar, Myret Ghabriel, Maha Yehia, Hala Taha, Dina Yassin, Sherine Salem, Khaled Shaaban, Mariem Omar, Shahenda M. El-Naggar. Molecular characterization of aggresome formation in choroid plexus carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1002. doi:10.1158/1538-7445.AM2015-1002