Data from High-Risk <i>TP53</i> Mutations Are Associated with Extranodal Extension in Oral Cavity Squamous Cell Carcinoma

Abstract

&lt;div&gt;Abstract&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; 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.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Experimental Design:&lt;/b&gt; 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.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; ENE was associated with decreased overall and disease-free survival. Mutation of the &lt;i&gt;TP53&lt;/i&gt; gene was the most common event in ENE&lt;sup&gt;+&lt;/sup&gt; OSCC. The frequency of &lt;i&gt;TP53&lt;/i&gt; mutation in ENE&lt;sup&gt;+&lt;/sup&gt; tumors was higher compared with ENE&lt;sup&gt;−&lt;/sup&gt; tumors and wild-type (WT) TP53 was highly represented in pN0 tumors. pN&lt;sup&gt;+&lt;/sup&gt;ENE&lt;sup&gt;+&lt;/sup&gt; patients had the highest proportion of high-risk &lt;i&gt;TP53&lt;/i&gt; mutations. Both primary tumors (PT) and lymph nodes with ENE (LN) exhibited a high rate of &lt;i&gt;TP53&lt;/i&gt; mutations (58.8% and 58.8%, respectively) with no significant change in allele frequency between the two tissue sites.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; 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 &lt;i&gt;TP53&lt;/i&gt; gene. Prospective clinical trials are required to determine whether &lt;i&gt;TP53&lt;/i&gt; mutational status can be used for personalized treatment decisions. &lt;i&gt;Clin Cancer Res; 24(7); 1727–33. ©2018 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;