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

Abstract

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.

Novel pathological predictive factors for extranodal extension in oral squamous cell carcinoma: a retrospective cohort study based on tumor budding, desmoplastic reaction, tumor-infiltrating lymphocytes, and depth of invasion

“…However, several ENEs are overlooked during clinical examinations due to limited radiological accuracy and the absence of a critical predictor of ENE. Recent studies have shown that TP53 mutation and SERPINE1 expression in fibroblasts increase the risk of ENE [ 40 , 41 ]. However, their abilities as predictors of ENE are limited, and the evaluation of these factors is difficult in routine work [ 40 , 41 ]; thus, a versatile and more simple method for supporting the cENE evaluation and predicting the presence of ENE using biopsy or surgically resected specimens of OSCC is required.…”

Novel Pathological Predictive Factors for Extranodal Extension in Oral Squamous Cell Carcinoma: a Retrospective Cohort Study Based on Tumor Budding, Desmoplastic Reaction, and Tumor-infiltrating Lymphocytes

“…These predictive factors could be simply evaluated using routine H&E staining and included in pathology reports. Few studies have examined the pathological predictive factors for ENE [40,41]. Gleber-Netto et al noted an increasing trend toward the frequency of ENE among patients with TP53mutant OSCC (65.5%) than among those with WT TP53 OSCC (42.1%; p=0.07) [40].…”

“…However, several ENEs are overlooked during clinical examinations due to limited radiological accuracy and the absence of a critical predictor of ENE. Recent studies have shown that TP53 mutation and SERPINE1 expression in broblasts increase the risk of ENE [40,41]. However, their abilities as predictors of ENE are limited, and the evaluation of these factors is di cult in routine work [40,41]; thus, a versatile and more simple method for supporting the cENE evaluation and predicting the presence of ENE using biopsy or surgically resected specimens of OSCC is required.…”

“…Few studies have examined the pathological predictive factors for ENE [40,41]. Gleber-Netto et al noted an increasing trend toward the frequency of ENE among patients with TP53mutant OSCC (65.5%) than among those with WT TP53 OSCC (42.1%; p=0.07) [40]. Dhanda et al showed that the combination of smooth muscle actin and SERPINE1 expression (4G/5G polymorphism) in CAF had superior sensitivity and speci city to MRI for the detection of ENE (sensitivity: 81%; speci city: 54%) [41].…”

Non-Invasive Saliva-based Detection of Gene Mutations in Oral Cancer Patients by Oral Rub and Rinse Technique

“…Several reports have shown the possible association of TP53 gene polymorphism in oral, breast, bladder, colorectal and lung cancers (Soulitzis et al, 2002;Katiyar et al, 2003;Zhu et al, 2007;Rivlin et al, 2011;Hanel and Moll 2012). TP53 mutations have shown to be associated with an increased risk of extranodal extensions in patients with advanced OSCC (Gleber-Netto et al, 2020). According to the IARC database (2018), 42.51% of head and neck cancers carry somatic mutations in TP53.…”