Functionally impactful TP53 mutations are associated with increased risk of extranodal extension in clinically advanced oral squamous cell carcinoma.

BACKGROUND: The treatment of advanced oral squamous cell carcinoma (OSCC) is a clinical challenge because it is unclear which therapeutic approaches are the best for this highly heterogeneous group of patients. Because TP53 mutations are the most common genetic event in these tumors, the authors investigated whether they could represent an ancillary biomarker in the management of advanced OSCC. METHODS: The TP53 gene was sequenced in 78 samples from patients with advanced OSCC who received treatment at 2 institutions located in the United States and Brazil. TP53 mutations were classified according to an in-silico impact score (the evolutionary action score of p53 [EAp53]), which identifies mutations that have greater alterations of p53 protein function (high-risk). Associations between TP53 mutation status/characteristics and clinicopathologic characteristics were investigated. The relevant findings were validated in silico by analyzing 197 samples from patients with advanced OSCC from The Cancer Genome Atlas. RESULTS: No differences in clinical outcomes were detected between patients with TP53-mutant and wild-type TP53 disease. However, patients who had tumors carrying high-risk TP53 mutations had a significantly increased risk of developing extranodal extension (ENE) compared with those who had wild-type TP53-bearing tumors. The increased chances of detecting ENE among patients who had high-risk TP53 mutations was validated among patients with advanced OSCC from The Cancer Genome Atlas cohort. CONCLUSIONS: High-risk TP53 mutations are associated with an increased chance of detecting ENE in patients with advanced OSCC. Because ENE is 1 of the major factors considered for OSCC patient management, TP53 mutation status may represent a potential ancillary biomarker for treatment decisions regarding postoperative adjuvant therapy.

Giant Cell Arteritis Masquerading as Tooth Pain: A Case Report.

Giant cell arteritis (GCA) is a form of vasculitis characterized by symptoms that often lead a patient to consult a general dentist. Its rarity in the dental setting and serious life-altering effects make it a formidable diagnosis. We discuss a case of a 60-year-old female with GCA presenting with primary symptoms of excruciating tooth and jaw pain on the left side. We also report secondary symptoms of headache and partial vision loss and engage in a review of the relevant literature. Jaw pain, unexplained toothache, or tissue necrosis in patients aged over 50 years can be misdiagnosed as joint arthritis or temporomandibular disease (TMD), which could lead to severe consequences. Accurately diagnosing this ophthalmic emergency is critical for implementing therapy promptly and preventing ischemic complications. Dentists should maintain a high index of suspicion about its signs and symptoms, which will aid in making an early diagnosis and prompt referral.

High-Risk TP53 Mutations Are Associated with Extranodal Extension in Oral Cavity Squamous Cell Carcinoma.

Purpose: Development of extranodal extension (ENE) has been associated with poor survival in patients with oral cavity squamous cell carcinoma (OSCC). Here, we sought to confirm the role of ENE as a poor prognostic factor, and identify genomic and epigenetic markers of ENE in order to develop a predictive model and improve treatment selection.Experimental Design: An institutional cohort (The University of Texas MD Anderson Cancer Center) was utilized to confirm the impact of ENE on clinical outcomes and evaluate the genomic signature of primary and ENE containing tissue. OSCC data from The Cancer Genome Atlas (TCGA) were analyzed for the presence of molecular events associated with nodal and ENE status.Results: ENE was associated with decreased overall and disease-free survival. Mutation of the TP53 gene was the most common event in ENE+ OSCC. The frequency of TP53 mutation in ENE+ tumors was higher compared with ENE- tumors and wild-type (WT) TP53 was highly represented in pN0 tumors. pN+ENE+ patients had the highest proportion of high-risk TP53 mutations. Both primary tumors (PT) and lymph nodes with ENE (LN) exhibited a high rate of TP53 mutations (58.8% and 58.8%, respectively) with no significant change in allele frequency between the two tissue sites.Conclusions: ENE is one of the most significant markers of OSCC OS and DFS. There is a shift toward a more aggressive biological phenotype associated with high-risk mutations of the TP53 gene. Prospective clinical trials are required to determine whether TP53 mutational status can be used for personalized treatment decisions. Clin Cancer Res; 24(7); 1727-33. ©2018 AACR.

The impact of intraoperative opioid use on survival after oral cancer surgery.

OBJECTIVES: To investigate the impact of opioid use on cancer recurrence after oral cancer surgery. We hypothesized that the amount of opioids administered during oral cancer surgery is an independent predictor of recurrence free survival (RFS) and overall survival (OS). METHODS: After Institutional Review Board approval, we collected demographic, tumor related, intraoperative and survival data of patients who had oral cancer surgery. Multivariable Cox proportional hazards models were used to determine the impact of important covariates on RFS and OS. RESULTS: 268 patients were included. After adjusting for significant covariates, the amount of opioids administered during surgery was not an independent predictor of RFS (HR: 1.27 [CI 95%, 0.838-1.924], p=0.26). However, we observed an association between opioid consumption and shorter OS (HR=1.77, [CI 95%=0.995-3.149]. p=0.05). CONCLUSIONS: High requirements of opioids during surgery increase the risk of recurrence and mortality by 27% and 77%, although the association is not statically significant.