Downregulation of CCL22 and mutated NOTCH1 in tongue and mouth floor squamous cell carcinoma results in decreased Th2 cell recruitment and expression, predicting poor clinical outcome.

OBJECTIVE: Tongue and mouth floor squamous cell carcinoma (T/MF SCC) exhibits a high rate of local recurrence and cervical lymph node metastasis. The effect of the tumor microenvironment on T/MF SCC remains unclear. MATERIALS AND METHODS: Transcriptome and somatic mutation data of patients with T/MF SCC were obtained from HNSC projects of the Cancer Genome Atlas. Immune infiltration quantification in early- (clinical stage I-II) and advanced-stage (clinical stage III-IV) T/MF SCC was performed using single sample Gene Set Enrichment Analysis and MCPcounter. Differentially expressed gene data were filtered, and their function was assessed through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Kaplan-Meier survival curve analysis and Cox regression model were conducted to evaluate the survival of patients with the CCL22 signature. Maftools was used to present the overview of somatic mutations. RESULTS: In T/MF SCC, T helper (Th)2 cell counts were significantly increased in patients with early-stage disease compared to those with advanced-stage disease. Expression of the Th2 cell-related chemokine, CCL22, was downregulated in patients with advanced-stage T/MF SCC. Univariate and multivariate Cox analyses revealed that CCL22 was a good prognostic factor in T/MF SCC. A nomogram based on the expression of CCL22 was constructed to serve as a prognostic indicator for T/MF SCC. NOTCH1 mutations were found at a higher rate in patients with advanced-stage T/MF SCC than in those with early-stage T/MF SCC, resulting in the inhibition of the activation of the NOTCH1-Th2 cell differentiation pathway. The expression levels of CCL22, GATA-3, and IL4 were higher in patients with early-stage T/MF SCC than in those with advanced-stage T/MF SCC. CONCLUSION: In T/MF SCC, high expression of CCL22 may promote the recruitment of Th2 cells and help predict a better survival. Mutations in NOTCH1 inhibit the differentiation of Th2 cells, facilitating tumor progression through a decrease in Th2 cell recruitment and differentiation.

Recurrence factors in pediatric ameloblastoma: Clinical features and a new classification system.

BACKGROUND: Ameloblastomas of jaw in the pediatric population are a rare clinical entity and have not been well addressed in the literatures. The present retrospective study analyzed the risk factors associated with recurrence of pediatric ameloblastomas. METHODS: Cases of primary pediatric ameloblastomas seen in a tertiary hospital between 2005 and 2015 were analyzed to identify the clinical factors associated with recurrence. RESULTS: There were a total of 104 cases of primary pediatric ameloblastomas. The overall mean maximum tumor diameter was 4.11 ± 1.339 cm. The receiver operating characteristic curve and the Youden Index showed an optimal cutoff point of 4.95 cm to accurately predict recurrence. Bone cortex/soft tissue invasion were associated with tumor recurrence (P < .001). CONCLUSIONS: The maximum tumor diameter, root resorption, and bone cortex/soft tissue invasion were risk factors for recurrence of pediatric ameloblastomas. The new classification system may serve as a predictor of recurrence in pediatric ameloblastomas.