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Aims: Primary mucoepidermoid carcinomas (MECs) of the sinonasal tract and nasopharynx are rare entities that represent a diagnostic challenge, especially in biopsy samples. Herein, we present a case series of MECs of the sinonasal and skull base and its mimics to evaluate the clinicopathological and molecular characteristics in order to avoid misdiagnosis. Methods: We reviewed the pathology records of patients diagnosed from 2014 to 2022. Thirty MECs were consecutively diagnosed during that period. Results: Based on morphological and fluorescence in situ hybridization (FISH) analyses, 30 tumors originally diagnosed as MECs were separated into MAML2 fusion-positive (7 cases) and MAML2 fusion-negative groups (23 cases), in which 14 tumors were positive for the EWSR1::ATF1 fusion; these tumors were reclassified to have hyalinizing clear cell carcinoma (HCCC). The remaining nine MAML2 FISH negative cases were reconfirmed as squamous cell carcinoma (SCC, 3 cases) which showed keratinization and high Ki-67 expression; DEK::AFF2 carcinomas (2 cases), in which DEK gene rearrangement was detected by FISH; and MECs as previously described (4 cases) with typical morphological features. Including 7 MAML2 rearrangements tumors, 11 MEC cases had a male-to-female ratio of 4.5:1, and 6 tumors arose from the nasopharyngeal region, while 5 tumors arose from the sinonasal region. The prognosis of this series of salivary gland-type MECs was favorable. Conclusions: Our study confirmed that HCCC runs the risk of being misdiagnosed as MEC in the sinonasal tract and nasopharynx, particularly with biopsy specimens. Careful histological evaluation with supporting molecular testing can facilitate pathological diagnoses. [ABSTRACT FROM AUTHOR]

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Purpose: To investigate the expression and prognostic value of c-Jun in hypopharyngeal squamous cell carcinoma (HPSCC).Methods: A retrospective study was performed on a cohort of 99 HPSCC patients. The expression of c-Jun and phosphorylated-c-Jun (p-c-Jun) was evaluated via immunohistochemistry (IHC) staining. Overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan-Meier method and multivariate Cox regression analysis.Results: The high expression of c-Jun and p-c-Jun in HPSCC accounted for 60.61% and 16.16%, respectively. High expression of c-Jun was closely associated with cT stage (p = 0.0401), tumor size (p = 0.0276), number of lymph node metastases (p = 0.0205) and pathological differentiation (p = 0.0108). The expression of c-Junhigh (p = 0.0043), p-c-Junhigh (p = 0.0376) and c-Junhigh/p-c-Junhigh were closely associated with poor OS. The Cox proportional multivariate hazard model revealed that lymphovascular invasion and c-Jun expression were independent influencing factors of OS in HPSCC patients.Conclusion: Our findings suggest that c-Jun is a reliable prognostic factors in HPSCC patients. [ABSTRACT FROM AUTHOR]

Background: Dysbiosis of the laryngeal microbiota has been demonstrated to the development of head and neck squamous cell carcinoma (HNSCC), but the association of Fusobacterium and Fusobacterium nucleatum (F. nucleatum) with DNA mismatch repair (MMR) and microsatellite instability (MSI) has not been investigated. Methods: The abundance of Fusobacterium and F. nucleatum, the status of deficient MMR (dMMR) and MSI, and MMR‐related gene expression were analyzed in 171 HNSCC tissues, 61 paired para‐tumor tissues, and 60 vocal cord polyp tissues. The molecular mechanism of F. nucleatum and MMR‐related gene expression were investigated in two human HNSCC cell lines (Tu 686 and FD‐LSC‐1). Results: Our results demonstrated that a high Fusobacterium abundance was detected in the HNSCC tissues and was exaggerated in the recurrent patients. We further found that a high Fusobacterium abundance was detected in the HNSCC tissues with dMMR and MSI. The Fusobacterium abundance was negatively correlated with the expression of MLH1, MSH2, and MSH6 in the HNSCC tissues. The Fusobacterium abundance was closely associated with the F. nucleatum abundance in the HNSCC tissues. F. nucleatum increased miR‐205‐5p expression to suppress MLH1, MSH2, and MSH6 expression via the TLR4‐ and MYD88‐dependent innate immune signaling pathway, resulting in dMMR, DNA damage, and cell proliferation in HNSCC. Conclusions: F. nucleatum impacts HNSCC epigenetic changes in tissues with dMMR to promote DNA damage and cell proliferation by suppressing MMR‐related gene expression via the TLR4/MYD88/miR‐205‐5p signaling pathway, which is valuable in the development of efficient strategies for HNSCC prevention and treatment. LAY SUMMARY: This study clearly indicates that Fusobacterium induced head and neck squamous cell carcinoma (HNSCC) aggressiveness to affect poor prognosis in HNSCC patients by epigenetic alteration of DNA mismatch repair (MMR) and microsatellite instability. Moreover, the research has shown that Fusobacterium nucleatum (F. nucleatum) impacts HNSCC epigenetic changes in tissues with deficient MMR to promote DNA damage and cell proliferation by suppressing MMRrelated gene expression via the TLR4/MYD88/miR‐205‐5p signaling pathway. [ABSTRACT FROM AUTHOR]

Background: This study is aimed at investigating the expressions and prognostic values of secreted or membrane-located proteins (SMPs) in laryngeal squamous cell carcinoma (LSCC). The correlations between the expressions of SMPs and immune cells' infiltrations were also investigated.Methods: The expression data of normal laryngeal and LSCC samples were obtained from the TCGA and GEO datasets. The differentially expressed SMPs were identified, and their prognostic values were analyzed. The biological functions of differentially expressed and worse-survival-related SMPs were explored. LASSO regression, Cox multivariate analysis, and nomogram were used to construct a model to predict the survival. Then, the infiltrations of the 24 immune cell populations were calculated using the GSVA method, and the correlations between the expression of SMPs and the immune infiltration were investigated.Results: 122 samples (12 normal and 120 LSCC) of the TCGA database and 114 samples (57 normal and 57 LSCC) of GSE127165 were included. We identified that 138 SMPs were significantly upregulated in LSCC samples of both the TCGA and GEO datasets, among which 52 SMPs were significantly correlated with worse survival. GO and KEGG analyses revealed those 52 SMPs significantly participate in tumor microenvironment and immune cells' communication. Nine of 52 SMPs (ABCC5, ATP1B3, CLEC11A, FLNA, FSTL3, MMP1, NME1, OAS3, and PHLDB2) were included in the nomogram to effectively and accurately predict the LSCC patients' survival. The expressions of most SMPs, such as MMP1 and FSTL3, were significantly positively correlated with the immune infiltration of LSCC.Conclusions: In this study, the expression, prognostic values, and correlations with immune infiltration of SMPs were analyzed in LSCC samples. Our analyses identified several significant SMPs differentially expressed between normal laryngeal and LSCC samples, correlated with worse survival, and related to the immune infiltration. [ABSTRACT FROM AUTHOR]

Background: It was recently suggested that the upregulation of podoplanin (PDPN) in cancer cells plays a significant role in tumor invasion and metastasis and that it is significantly associated with poor prognosis in oral, cutaneous, and esophageal squamous cell carcinoma. The aim of this study was to investigate the expression pattern of PDPN in sinonasal squamous cell carcinoma (SNSCC) and to evaluate its role as a prognostic factor for survival outcome. Patients and methods: This study included 59 subjects with SNSCC. We retrospectively collected the clinical features of these patients from medical records and retrieved the associated formalin-fixed, paraffin-embedded tissues for PDPN immunohistochemical staining. Furthermore, PDPN expression was analyzed in relation to the patients' clinicopathological features and prognosis. Results: We observed positive staining for PDPN in both cancer cells and stromal cancer-associated fibroblasts (CAFs). Positive expression of PDPN in cancer cells of patients with SNSCC was significantly correlated with the primary tumor site (p = 0.009) and local recurrence (p = 0.024). In addition, patients with PDPN-positive cancer cells had significantly lower overall survival (OS) and disease-free survival (DFS) rates than did patients with PDPN-negative cancer cells (both p < 0.05). Multivariate analysis revealed that PDPN expression in cancer cells was an independent prognostic factor for both OS (p = 0.038) and DFS (p = 0.039). Conclusions: Our findings demonstrated that PDPN overexpression may be both an independent prognostic biomarker and a therapeutic target in SNSCC. [ABSTRACT FROM AUTHOR]

Background: Cancer cells induce the infiltration of various immune cells that are located or distributed in different sites and play multiple roles, which have recently been proposed to predict clinical outcomes. We therefore studied the prognostic significance of the presence of tumour-infiltrating lymphocytes (TILs) and the ratios between different types of immune cells in hypopharyngeal squamous cell carcinoma (HPSCC).Methods: We retrospectively analysed 132 consecutive patients diagnosed with advanced HPSCC in 2013-2017. Tumoural parenchyma was immunohistochemically counted manually for the number of CD8, CD4 and Foxp3 cells. The ratios of CD8/Foxp3 and CD8/CD4 ratios were calculated for each specimen and analyzed with respect to patient clinicopathological variables and prognosis.Results: HPSCC patients with high levels of TILs showed evident correlations with well differentiated tumors (P < 0.05). Moreover, Foxp3+ TIL is also associated with overall staging group and T category (P = 0.048 and P = 0.046, respectively). Kaplan-Meier analysis showed that high CD8 and FoxP3 infiltration correlated with favourable overall survival (OS, P = 0.019 and P = 0.001), disease-free survival (DFS, P = 0.045 and P = 0.028) and distant metastasis-free survival (DMFS, P = 0.034 and P = 0.009), respectively, but only Foxp3 displayed prognostic significance for DMFS in multivariate analysis (MVA). In the lymphocyte ratio analysis, CD8/Foxp3 appeared to play a pivotal role, and patients with a high CD8/Foxp3 ratio had a superior 3-year DFS and DMFS compared with those a low CD8/Foxp3 ratio in both univariate analysis (UVA) and MVA (P = 0.015 and P = 0.011). A high CD8/CD4 ratio was associated with better DFS and local relapse-free survival (LRFS) in UVA, and was an independent prognostic factor for improved LRFS in MVA (P = 0.040).Conclusion: Although high TILs levels were determined to be prognostically significant in advanced HPSCC, the ratios of these subsets may be more informative. Particularly, a higher ratio of CD8/Foxp3 accurately predicts prognosis for improved DFS and DMFS, and an increased CD8/CD4 ratio is an independent predictor for favourable LRFS. [ABSTRACT FROM AUTHOR]

Advanced laryngeal squamous cell carcinoma (LSCC) has a high mortality rate, and the prognosis is poor. However, the underlying molecular biological mechanisms bringing about the development and progression of advanced LSCC are not entirely clarified. This study aimed to find out the potential biomarkers to predict the prognosis in advanced LSCC patients who had undergone postoperative radiotherapy alone. The next-generation sequencing of RNA was performed to detect the mRNAs expression profiling in 10 advanced LSCC samples, comprised of 5 samples from LSCC patients with favorable outcome and 5 samples from paired patients with poor outcome. Then bioinformatics analysis including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were used to find out functional core genes that were significantly different between the two groups. 1630 differentially expressed genes (DEGs) were confirmed to have significant differences between the two groups. 53 GO terms and 19 pathways which were closely related to the DEGs were identified. Finally, 52 intersection DEGs which were both related to the top three GO terms and pathways were identified. The expression of several core genes was confirmed with RT-qPCR in tissues from another 75 patients. RT-qPCR confirmed that the genes of c-JUN, LYN, PIK3R2, and TNFAIP3 were significantly differentially expressed between the two groups, which was in accordance with the RNA sequencing data. The DEGs identified above may be potential prognostic markers for advanced LSCC patients with postoperative radiotherapy, and may provide essential guidance for following-up. [ABSTRACT FROM AUTHOR]

Objectives: Limited information is available regarding programmed death-ligand 1 (PD-L1) and tumor-infiltrating lymphocytes (TILs) in hypopharyngeal squamous cell carcinoma (HPSCC). Therefore, we investigated the expression of PD-L1 and the volume of TILs in HPSCC to determine whether these biomarkers were associated with patient clinicopathologic characteristics and prognosis. Furthermore, we explored p16 status and analyzed its possible correlations with clinical outcomes.Methods: Tissues of 111 HPSCC patients were immunohistochemically analyzed for PD-L1, CD8, CD4, and Foxp3 expression to assess the microenvironment. We also assessed the p16 status. The expression of PD-L1 and TILs were analyzed with respect to patient clinicopathologic variables and prognosis.Results: Twenty-four (21.6%) patients had PD-L1 expression in ≥1% of tumor cells. PD-L1 expression was significantly correlated with a high level of TILs (P < 0.05). Kaplan-Meier analysis showed that higher CD8+ and FoxP3+ TIL infiltration was strongly associated with superior overall survival (OS, P = 0.005 and P = 0.008) and disease-free survival (DFS, P = 0.015 and P = 0.048). Univariate and multivariate analyses confirmed that CD8+ TIL exhibited strong prognostic significance. The combination of PD-L1+ with CD8high expression was a prognostic factor and was associated with better OS (P = 0.025). Moreover, p16 positivity was detected in five patients (4.5%) and was only occasionally involved in HPSCC.Conclusion: Our findings indicate that high CD8 and FoxP3 expression in HPSCC contributes to longer patient survival. Although PD-L1 expression was not associated with outcome, PD-L1 positivity in combination with CD8high expression may have greater predictive potential. [ABSTRACT FROM AUTHOR]