Oncogenic drivers in 11q13 associated with prognosis and response to therapy in advanced oropharyngeal carcinomas.

OBJECTIVES: To identify potential molecular drivers associated with prognosis and response to treatment in advanced oropharyngeal squamous cell carcinomas (OPSCC). MATERIALS AND METHODS: Thirty-three OPSCC biopsies from untreated Brazilian patients were evaluated for human papilloma virus genotyping, genome wide copy number alterations and gene expression profiling. Data were integrated using CONEXIC algorithm. Validation with TCGA dataset and confirmation by RT-qPCR of candidate genes were performed. RESULTS: High-risk HPV positive cases, detected in 55% of advanced OPSCC, were associated with better outcome. Losses of 8p11.23-p11.22, 14q11.1-q11.2 and 15q11.2, and gains of 11q13.2 and 11q13.2-q13.3 were detected as recurrent alterations. Gains of 3q26.31 and 11q13.2 and losses of 9p21.3 were exclusively detected in HPV-negative tumors. Two clusters of expression profiles were observed, being one composed mostly by HPV positive cases (83%). HPV-positive enriched cluster showed predominantly immune response-related pathways. Integrative analysis identified 10 modulators mapped in 11q13, which were frequently cancer-related. These 10 genes showed copy number gains, overexpression and an association with worse survival, further validated by TCGA database analyses. Overexpression of four genes (ORAOV1, CPT1A, SHANK2 and PPFIA1) evaluated by RT-qPCR confirmed their association with poor survival. Multivariate analysis showed that PPFIA1 overexpression and HPV status are independent prognostic markers. Moreover, SHANK2 overexpression was significantly associated with incomplete response to treatment. CONCLUSION: The integrative genomic and transcriptomic data revealed potential driver genes mapped in 11q13 associated with worse prognosis and response to treatment, giving fundamentals for the identification of novel therapeutic targets in OPSCC.

Warthin's tumour of the parotid gland: our experience.

Benign tumours account for approximately 60-80% of parotid neoplasms and among these, Warthin's tumour is the second most common benign neoplasm accounting for approximately 15% of all parotid epithelial tumours. The medical records of 100 consecutive patients with Warthin's tumour of the parotid gland admitted for treatment at the Department of Head and Neck Surgery and Otorhinolaryngology, Hospital A.C. Camargo, São Paulo, Brazil, between 1983 and 2011 were retrospectively analyzed. The surgical procedures included 104 (96%) subtotal parotidectomies and 4 (3.7%) total parotidectomies. One hundred and eight parotidectomies were performed in 100 patients with Warthin's tumour. Postoperative complications occurred in 67 (62.3%) of surgical procedures, and facial nerve dysfunction was the most frequent complication, occurring in 51 of 108 surgeries (47.2%). The marginal mandibular branch of the facial nerve was affected in 46 of the 48 cases (95.8%) of facial nerve dysfunction. Frey's syndrome was diagnosed in the late postoperative period in 19 patients (17.6%). We conclude that either superficial or total parotidectomy with preservation of facial nerve are the treatment of choice for Warthin's tumour with no case of recurrence seen after long-term follow-up. Facial nerve dysfunction and Frey's syndrome were the main complications associated with this surgery. Thus, if on one hand total parotidectomy is an appropriate radical resection of parotid parenchyma reducing, in theory, the risk of recurrence, on the other hand superficial parotidectomy is also a radical and efficient method with lower morbidity in terms of facial nerve dysfunction and Frey's syndrome.