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

Armando Baptista,João Vinagre,Paula Soares,Rui Batista,Manuel António Campos,Ana Pestana,Joana Pardal,Sofia Macedo,José Manuel Lopes,Agostinho Sanches,Margarida Sá Fernandes

doi:10.3390/genes11070751

Abstract

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

Highlights

Cutaneous squamous cell carcinoma is the second-most-common skin cancer in Caucasians and cumulative ultraviolet radiation is considered the major ethiopathogenic factor [1,2].cutaneous squamous cell carcinoma (cSCC) carcinogenesis includes premalignant lesions (actinic keratosis (AK) and in situ squamous carcinoma/Bowen’s disease), invasive, and metastatic cSCCs, a multistep model is not always detected [3]
We recently reported the association of TERT promoter mutations with worse prognosis but we admit that its putative prognostic significance still needs to be established in larger series [12]
162 cases) and the mean p53 overexpression was 1+ h-score (91.6 ± 5.9), Table 1. p53 overexpression was observed in 82.1% of the cases (74.2% of the in situ and 84.0% of the invasive cSCCs), Table 1

Summary

Introduction

Cutaneous squamous cell carcinoma (cSCC) is the second-most-common skin cancer in Caucasians and cumulative ultraviolet radiation is considered the major ethiopathogenic factor [1,2].cSCC carcinogenesis includes premalignant lesions (actinic keratosis (AK) and in situ squamous carcinoma/Bowen’s disease), invasive, and metastatic cSCCs, a multistep model is not always detected [3]. Committee on Cancer (AJCC) guidelines [5] and for head and neck cutaneous squamous cell carcinoma the recent 8th edition of the AJCC [6]. Clinicopathological prognostic markers have been reported in cSCC for recurrence (tumor thickness > 2 mm and >6 mm, invasion beyond subcutaneous fat, perineural invasion, tumor size > 2 cm, and poor differentiation and location in the temple) and metastasis (tumor thickness > 2 mm and >6 mm, invasion beyond subcutaneous fat, perineural invasion, tumor size > 2 cm, poor differentiation, immunosuppression, and location in the temple, lip, and ear) [11]. We recently reported the association of TERT promoter mutations with worse prognosis (recurrence and metastasis) but we admit that its putative prognostic significance still needs to be established in larger series [12]

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