Penile cancer is a rare cancer in developed countries, but it has a higher incidence in developing countries such as Asia, Africa, and South America 1,2. Despite its rarity, the disease significantly affects the patient’s life when it does occur. Localized disease can be managed by surgical resection (partial or total penectomy) or penis-preserving surgery and radiotherapy. In patients with a higher T stage or grade, or clinically positive inguinal lymph nodes, an inguinal lymph node dissection is usually performed. If nonregional lymph nodes are involved or if metastatic disease is present, surgical cure cannot be obtained.
In these cases of advanced disease, surgery with or without radiation is often used for palliation and local control. Metastatic disease, which can involve distant lymph nodes, lung, liver, brain, and bone, is often managed with chemotherapy. Chemotherapy in this situation has been poorly studied (no randomized trials), responses are often partial and of short duration, and therapy is associated with significant toxicity 3–7. Thus, it is imperative that new therapies be investigated for this rare but devastating disease.
Since the end of the 1980s, an understanding of the molecular biology of cancer has immensely increased the understanding of tumour biology. Using this knowledge, scientists and clinicians are turning to novel treatments to exploit specific molecular targets. Tumour growth and progression depend on a number of pathways involving receptors at the cell membrane surface that control intracellular signalling pathways. One important pathway involves the cell-surface receptor epidermal growth factor receptor (egfr) 8. Epidermal growth factor and other ligands bind to and activate egfr to activate signalling pathways that regulate cell proliferation, migration, adhesion, differentiation, and apoptosis.
In a number of solid tumours, including brain, lung, breast, prostate, stomach, and head and neck, egfr can be overexpressed or mutated, leading to deregulation of related pathways. Overstimulation of egfr-mediated signalling can contribute to uncontrolled cell division and thus to oncogenic signalling and tumour angiogenesis and metastasis, protecting cancer cells from undergoing apoptosis. In some malignancies, overexpression or excessive activation of egfr tends to be associated with a more aggressive malignant phenotype, with greater metastatic potential and worse prognosis 9–11.
To our knowledge, no studies have evaluated the expression of egfr in invasive squamous cell carcinoma of the penis. Given egfr overexpression, and the success with egfr-directed therapy in other tumours, we felt it worthwhile to pursue this area of research in penile cancer. Thus, the objective of the present study was to characterize the expression of egfr in cases of invasive squamous cell carcinoma of the penis. If overexpression were to be seen, then exploiting the egfr pathway as a therapeutic target in advanced penile cancer would be a rational approach.