Prognostic Significance of RAS Mutations and P53 Expression in Cutaneous Squamous Cell Carcinomas

Abstract

<i>TP53</i> is considered the most commonly-altered gene in cutaneous squamous cell carcinoma (cSCC). Conversely, <i>RAS</i> mutations have been reported in a low percentage of cSCC. The objective of our study was to evaluate the frequency of p53 expression and <i>RAS</i> mutations in cSCC and correlate them with clinicopathological features and patient outcome. We performed immunohistochemistry for p53 and genetic profiling for <i>RAS</i> mutations in a retrospective series of cSCC. The predictive value of p53 expression, <i>RAS</i> mutations, and clinicopathological parameters was assessed using logistic regression models. The overall frequency of <i>RAS</i> mutations was 9.3% (15/162), and 82.1% of the cases (133/162) had p53 overexpression. <i>RAS</i> mutations rate was 3.2% (1/31) of in situ cSCCs and 10.7% (14/131) of invasive cSCCs. <i>RAS</i> mutations were more frequently associated with an infiltrative than an expansive pattern of invasion (<i>p</i> = 0.046). p53 overexpression was a predictor of recurrence in the univariate analysis. Our results indicate that <i>RAS</i> mutations associate with features of local aggressiveness. Larger studies with more recurrent and metastatic cSCCs are necessary to further address the prognostic significance of p53 overexpression in patients' risk stratification.