ABSTRACT
BACKGROUND: Resection of parotid carcinomas involving the parapharyngeal space is challenging. How this affects tumor margin control, recurrence, and survival is unclear. METHODS: Patients who underwent resection of parotid carcinomas between 1985 and 2015 at Memorial Sloan Kettering Cancer Center were evaluated for the impact of parapharyngeal extension (PPE) on margin status, local recurrence-free probability (LRFP), and disease-specific survival (DSS). RESULTS: Out of 214 patients in whom preoperative imaging was available for review, 22 (10.3%) had PPE. Matched by histotypes, carcinomas with PPE had comparable margin positivity (p = 0.479), T classification (p = 0.316), pathologic risk (p = 0.936), and adjuvant therapy (p = 0.617) to those without PPE. The 3-year LRFP was 88.9% versus 95.4% (hazard ratio [HR] 2.23 after adjusting for pT classification, p = 0.342) and the 5-year DSS was 74.2% versus 69.5% (adjusted HR 0.45, p = 0.232) in patients with and without PPE. CONCLUSION: PPE does not appear to worsen oncologic outcomes in the resection of parotid carcinomas.
Subject(s)
Carcinoma , Parotid Neoplasms , Humans , Margins of Excision , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/surgery , Neoplasm Staging , Parotid Neoplasms/pathology , Parotid Neoplasms/surgery , Retrospective StudiesABSTRACT
OBJECTIVES: We have previously identified and validated a panel of molecular prognostic markers (ATP13A3, SSR3, and ANO1) for Head and Neck Squamous Cell Carcinoma (HNSCC). The aim of this study was to investigate the consequence of ATP13A3 dysregulation on signaling pathways, to aid in formulating a therapeutic strategy targeting ATP13A3-overexpressing HNSCC. MATERIALS AND METHODS: Gene Set Enrichment Analysis (GSEA) was performed on HNSCC microarray expression data (Internal local dataset [n = 92], TCGA [n = 232], EMBL [n = 81]) to identify pathways associated with high expression of ATP13A3. Validation was performed using immunohistochemistry (IHC) on tissue microarrays (TMAs) of head and neck cancers (n = 333), staining for ATP13A3 and phosphorylated Aurora kinase A (phospho-T288). Short interfering RNA was used to knockdown ATP13A3 expression in patient derived HNSCC cell lines. Protein expression of ATP13A3 and Aurora kinase A was then assessed by immunoblotting. RESULTS: GSEA identified Aurora kinase pathway to be associated with high expression of ATP13A3 (p = 0.026). The Aurora kinase pathway was also associated with a trend towards poor prognosis and tumor aggressiveness (p = 0.086, 0.094, respectively). Furthermore, the immunohistochemical staining results revealed a significant association between Aurora kinase activity and high ATP13A3 expression (p < 0.001). Knockdown of ATP13A3 in human head and neck cell lines showed decrease in Aurora kinase A levels. CONCLUSION: Tumors with high ATP13A3 are associated with high Aurora kinase activity. This suggests a potential therapeutic role of Aurora kinase inhibitors in a subset of poor prognosis HNSCC patients with overexpression of ATP13A3.
Subject(s)
Adenosine Triphosphatases/metabolism , Aurora Kinase A/metabolism , Head and Neck Neoplasms/metabolism , Membrane Transport Proteins/metabolism , Protein Kinase Inhibitors/therapeutic use , Signal Transduction , Squamous Cell Carcinoma of Head and Neck/metabolism , Adenosine Triphosphatases/genetics , Aurora Kinase A/antagonists & inhibitors , Cell Line, Tumor , Female , Gene Silencing , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/genetics , Head and Neck Neoplasms/pathology , Humans , Immunohistochemistry , Male , Membrane Transport Proteins/genetics , Molecular Targeted Therapy/methods , Prognosis , RNA, Small Interfering , Signal Transduction/genetics , Squamous Cell Carcinoma of Head and Neck/drug therapy , Squamous Cell Carcinoma of Head and Neck/genetics , Squamous Cell Carcinoma of Head and Neck/pathology , Tissue Array AnalysisABSTRACT
BACKGROUND: Patients with head and neck cancer have a higher risk of emergency department (ED) frequent attender (FA). We hypothesized that FAs present with issues different from non-FAs. METHODS: A retrospective cohort study was conducted on Singapore residents with head and neck cancers using de-identified registry merged with electronic medical record data. A competing risk regression analysis was performed to identify factors associated with FA. Aggregated primary diagnoses were compared for patients with and without FA risk factors. RESULTS: Thirteen percent of patients with head and neck cancer were FAs. FA risk factors were Charlson comorbidity index (3+), and socioeconomic status (SES). FAs had a higher proportion of respiratory infections. The spectrum of diagnosis was similar for patients with low and high SES. Current smokers had a greater proportion of respiratory complaints, relative to never smokers. CONCLUSION: Patients with greater comorbidity scores or higher SES were more likely to be FA. FAs were more likely to present with respiratory complaints, likely related to cancer treatment, or smoking status.