The expression of a mutant epidermal growth factor receptor in prostatic tumours

The article is a synopsis of a thesis [1] presented at the University of Leicester. Carcinoma of the prostate is now the most commonly diagnosed cancer in men and is thus a signi®cant cause of morbidity and mortality [2]. However, the factors that govern the natural history of the disease remain poorly understood. Research efforts are therefore increasingly focused on the molecular and cellular pathways that regulate normal and abnormal growth of the gland. Peptide growth factors and their receptors are cellular signalling molecules that are an integral part of the regulatory pathways/mechanisms in solid-organ homeostasis [3]. Of these proteins, wild-type EGFR (WT-EGFR) has been most commonly implicated in carcinogenesis, but studies on WT-EGFR expression in prostatic tumours have produced con ̄icting results [4,5]. Despite this, more speci®c investigative methods now indicate a progressive depletion of the receptor as prostatic tissues become increasingly malignant [6]. The progressive loss of WTEGFR in prostatic tumours has remained unexplained, although several mechanisms have been proposed, including the expression of a mutated receptor. The most common mutant EGFR found in human cancers is the Type III mutant (EGFRvIII), which is a constitutively active tyrosine kinase that is able to initiate cell division independently of the ligand, and thus (potentially) independently of hormonal control [7]. This aberrant EGFR has been implicated in the pathogenesis and progression of several cancers but has not been detected in prostate cancer.