Abstract
Penile Squamous Cell Carcinoma (SCC) is a rare cancer with poor prognosis and limited response to conventional chemotherapy. The genetic and epigenetic alterations of Epidermal Growth Factor Receptor (EGFR)-RAS-RAF signaling in penile SCC are unclear. This study aims to investigate four key members of this pathway in penile SCC. We examined the expression of EGFR and RAS-association domain family 1 A (RASSF1A) as well as the mutation status of K-RAS and BRAF in 150 cases of penile SCC. EGFR and RASSF1A expression was evaluated by immunohistochemistry. KRAS mutations at codons 12 and 13, and the BRAF mutation at codon 600 were analyzed on DNA isolated from formalin fixed paraffin embedded tissues by direct genomic sequencing. EGFR expression was positive in all specimens, and its over-expression rate was 92%. RASSF1A expression rate was only 3.42%. Significant correlation was not found between the expression of EGFR or RASSF1A and tumor grade, pT stage or lymph node metastases. The detection of KRAS and BRAF mutations analysis was performed in 94 and 83 tumor tissues, respectively. We found KRAS mutation in only one sample and found no BRAF V600E point mutation. In summary, we found over-expression of EGFR in the majority cases of penile SCC, but only rare expression of RASSF1A, rare KRAS mutation, and no BRAF mutation in penile SCC. These data suggest that anti-EGFR agents may be potentially considered as therapeutic options in penile SCC.
Highlights
Penile squamous cell carcinoma (SCC) is a relatively rare disease and accounts for less than 1% of all male malignancies in Europe and North America [1]
To identify the potential role of Epidermal Growth Factor Receptor (EGFR)-RAS-RAF signaling in penile SCC, we investigated four key members (EGFR expression, RAS-association domain family 1 A (RASSF1A) expression, K-RAS mutations, and BRAF mutations) of this pathway in 150 cases of penile SCC
Over-expressed EGFR was found in 92% of the penile SCC cases, and loss of RASSF1A protein expression was found in 96.67% of the cases
Summary
Penile squamous cell carcinoma (SCC) is a relatively rare disease and accounts for less than 1% of all male malignancies in Europe and North America [1]. Because of its low incidence, penile SCC treatments have been rarely studied and reported in the literature. Surgery is the first choice for localized, resectable penile SCC. Chemotherapeutic agents showed limited effectiveness with a short-term response rate of less than 30% and a 3-year survival rate of less than 10% for metastatic penile cancer [2,3]. There is an urgent need to develop new treatment strategies for penile SCC. Little work has been done to evaluate their effectiveness in penile SCC. Elucidation of the molecular pathways involved in penile SCC is essential for understanding the pathogenesis of and developing new treatment strategies for this rare disease
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