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

Author(s)

Gleber-Netto, Frederico O. ; Neskey, David ; de Mattos Costa, Ana Flavia ; Kataria, Pranav ; Rao, Xiayu ; Wang, Jing ; Kowalski, Luiz Paulo ; Pickering, Curtis R. ; Dias-Neto, Emmanuel ; Myers, Jeffrey N.

• Document type: Journal article
• Source: Cancer; v. 126, n. 20, p. 13-pg., 2020-08-14.

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. BecauseTP53mutations 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 TheTP53gene was sequenced in 78 samples from patients with advanced OSCC who received treatment at 2 institutions located in the United States and Brazil.TP53mutations 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 betweenTP53mutation 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 withTP53-mutant and wild-typeTP53disease. However, patients who had tumors carrying high-riskTP53mutations had a significantly increased risk of developing extranodal extension (ENE) compared with those who had wild-typeTP53-bearing tumors. The increased chances of detecting ENE among patients who had high-riskTP53mutations was validated among patients with advanced OSCC from The Cancer Genome Atlas cohort. Conclusions High-riskTP53mutations 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,TP53mutation status may represent a potential ancillary biomarker for treatment decisions regarding postoperative adjuvant therapy. (AU)

• FAPESP's process: 13/09142-2 - Study of salivary markers of nodal metastasis in oral squamous cell carcinoma
• Grantee: Frederico Omar Gleber Netto
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 11/13315-4 - Large-scale study of transcriptional alterations associated with the development of metastasis in oral cancer.
• Grantee: Frederico Omar Gleber Netto
• Support Opportunities: Scholarships in Brazil - Doctorate