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

Abstract

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.

Epidermal growth factor receptor gaining impact in cutaneous squamous cell carcinoma

“…The association of EGFR expression levels with progression in HNSCC has been seen in multiple but not all studies . One critical issue affecting many studies, including the current study by Cañueto et al ., is that IHC has its weaknesses, in particular being only semi‐quantitative, and results varying considerably due to technical‐ and evaluation‐based differences. Achieving staining and evaluation protocols that are reproducible for CSCC across various centres could prove challenging.…”

“…The role of EGFR in CSCC is less well documented. The current study by Cañueto et al . analyses a sizeable cohort of 94 CSCCs assessing EGFR expression levels by immunohistochemistry (IHC), fluorescence in situ hybridization (FISH) and quantitative polymerase chain reaction (qPCR).…”

“…This occurs more frequently in immunosuppressed patients, a correlation which surprisingly was not observed in the Cañueto et al . study . Determining potential biomarkers such as EGFR, which identify the rare tumours with more aggressive behaviour, will be of considerable relevance for clinicians.…”

Investigating therapeutic possibilities for treatment of perineural invasion

“…EGFR dysregulation and overexpression is a common theme in roughly one third of epithelial malignancies including SCCHN, breast, colorectal, ovarian, pancreatic, prostate, glioblastoma, and non-small cell lung cancer (NSCLC) with the magnitude of EGFR overexpression correlating to cancer growth and invasiveness (126,154). In cSCC, EGFR overexpression has been detected in 35% (33/94) of primary lesions and up to 47% (7/15) of nodal metastases (155,156). Other studies have illustrated EGFR overexpression in primary cSCC to be up to 56% (28/50) (157).…”

“…Other studies have illustrated EGFR overexpression in primary cSCC to be up to 56% (28/50) (157). EGFR overexpression was also associated with poor prognostic implications, portending tumour proliferation, locoregional, and lymphatic spread as an independent factor (155). PNI is a form of metastasis whereby tumour cells infiltrate nerves, but this has not been well characterised for EGFR expression.…”