Multiple primary tumors can occur in up to 35 % of the patients with head and neck cancer, however its clinicopathological features remain controversial. Deregulation of epithelial-mesenchymal transition (EMT) signaling has been associated with aggressive malignancies and tumor progression to metastasis in several cancer types. This study is the first to explore EMT process in multiple primary oral squamous cell carcinomas (OSCC). Immunohistochemical analysis of E-cadherin, catenin (α, β, and γ), APC, collagen IV, Ki-67, cyclin D1, and CD44 were performed in a tissue microarray containing multiple representative areas from 102 OSCC patients followed-up by at least 10 years. Results were analysed in relation to clinicopathological characteristics and survival rates in patients presenting multiple primary tumors versus patients without second primary tumors or metastatic disease. Significant association was observed among multiple OSCCs and protein expression of E-cadherin (P = 0.002), β-catenin (P = 0.047), APC (P = 0.017), and cyclin D1 (P = 0.001) as well as between lymph nodes metastasis and Ki-67 staining (P = 0.021). OSCCs presenting vascular embolization were associated with negative β-catenin membrane expression (P = 0.050). There was a significantly lower survival probability for patients with multiple OSCC (log-rank test, P < 0.0001), for tumors showing negative protein expression for E-cadherin (log-rank test, P = 0.003) and β-catenin (log-rank test, P = 0.031). Stratified multivariate survival analysis revealed a prognostic interdependence of E-cadherin and β-catenin co-downexpression in predicting the worst overall survival (log-rank test, P = 0.007). EMT markers have a predicted value for invasiveness related to multiple primary tumors in OSCC and co-downregulation of E-cadherin and β-catenin has a significant prognostic impact in these cases.
Metastatic oral squamous cell carcinoma (OSCC) is frequently associated with recurrent gene abnormalities at specific chromosomal loci. Here, we utilized array comparative genomic hybridization and genome-wide screening of metastatic and non-metastatic tongue tumors to investigate genes potentially contributing to OSCC progression to metastasis. We identified predominant amplifications of chromosomal regions that encompass the RAB5, RAB7 and RAB11 genes (3p24-p22, 3q21.3 and 8p11–12, respectively) in metastatic OSCC. The expression of these Rab GTPases was confirmed by immunohistochemistry in OSCC tissues from a cohort of patients with a follow-up of 10 years. A significant overexpression of Rab5, Rab7 and Rab11 was observed in advanced OSCC cases and co-overexpression of these Rabs was predictive of poor survival (log-rank test, P = 0.006). We generated a Rab interaction network and identified central Rab interactions of relevance to metastasis signaling, including focal adhesion proteins. In preclinical models, mRNA and protein expression levels of these Rab members were elevated in a panel of invasive OSCC cell lines, and their down-regulation prevented cell invasion at least in part via inhibition of focal adhesion disassembly. In summary, our results provide insights into the cooperative role of Rab gene amplifications in OSCC progression and support their potential utility as prognostic markers and therapeutic approach for advanced OSCC.
ObjectivesThe reported prevalence of vestibular dysfunction after cochlear implantation (CI) is varies between different scientific papers. The aim of this study is to determine the reported post-implantation outcome in terms of dizziness, and to measure its impact on quality of life using the Dizziness handicap inventory (DHI).MethodsThis was a prospective questionnaire based study of postoperative cochlear implant patients. The questionnaire assessed the type and onset of dizziness in addition to the DHI.Results122 patients were recruited in this study, which is the largest sample size in the literature reported so far. Dizziness was evident in 45.9% of the population post-CI and in 27% pre-CI. The commonest subtype of the dizziness was unsteadiness followed by lightheadedness. The dizziness was mild in most of the patients.ConclusionAlthough mild, dizziness is a common complaint post-cochlear implantation. An understanding of symptoms helps counsel patients preoperatively.
Keratosis obturans is an obscure entity characterized by accumulation of desquamated keratinous material in the bony portion of the external auditory canal. Patients with this condition typically present with severe otalgia, conductive hearing loss, and global widening of the external auditory canal. We present a case of keratosis obturans that was misdiagnosed as impacted wax. The case was diagnosed and managed by microscope-guided examination with the patient under general anesthesia.
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