Epidermal growth factor receptor expression is associated with poor outcome in cutaneous squamous cell carcinoma

Summary Background Cutaneous squamous cell carcinoma (CSCC) is the second most frequent cancer in humans after basal cell carcinoma, and its incidence is dramatically rising. CSCC is rarely problematic, but given its high frequency, the absolute number of complicated cases is also high. It is necessary to identify molecular markers in order to recognize those CSCCs with poor prognosis. There is controversy concerning the role of epidermal growth factor receptor (EGFR) as a marker of prognosis in CSCC. In addition, EGFR‐targeted therapies have emerged in recent years and a better understanding of the role of EGFR in CSCC may be of help for some patients in predicting prognosis and guiding curative management. Objectives To evaluate the role of EGFR as a prognostic factor in CSCC. Methods We evaluated clinical and histopathological features, including events of poor clinical evolution, in a series of 94 cases of CSCC. We also analysed EGFR expression by immunohistochemistry, fluorescent in situ hybridization and quantitative polymerase chain reaction. Results We detected EGFR in 85 cases (90%), with overexpression in 33 cases (35%), and aberrant EGFR expression in the cytoplasm in 50 cases (53%). EGFR overexpression in the primary tumours was associated with lymph node progression, tumour–nodes–metastasis stage progression and proliferation (Ki‐67 staining) in CSCC. EGFR overexpression and poor grade of differentiation were the strongest independent variables defining lymph node metastasis and progression in CSCC in a logistic regression model. Conclusions We demonstrate that EGFR overexpression has prognostic implications associated with lymph node metastasis and progression in CSCC. What's already known about this topic? Cutaneous squamous cell carcinoma (CSCC) is the second most frequent cancer in humans and sometimes exhibits a poor outcome. Epidermal growth factor receptor (EGFR) activation in keratinocytes induces cellular proliferation, increases cell survival and induces resistance to apoptosis. While the expression of EGFR has been extensively studied in CSCC, there is some controversy surrounding its prognostic significance. What does this study add? Based on the results of our study, EGFR overexpression appears to have prognostic implications associated with lymph node metastasis and progression in CSCC. There was no association between the level of EGFR protein, detected by immunohistochemistry, and the level of EGFR RNA. What is the translationa