Alterations in the expression of androgen receptor, wild type-epidermal growth factor receptor and a mutant epidermal growth factor receptor in human prostate cancer

Abstract

Prostatic carcinogenesis has been associated with alterations in the expression of the androgen receptor (AR) and the epidermal growth factor receptor (WT-EGFR), and over-expression of the constitutively active variant epidermal growth factor receptor (EGFRvI 11). Changes in the expression of AR, WT-EGFR and EGFRvlII were evaluated in serial sections from 26 normal and 26 benign hyperplastic and 50 prostate cancer tissues using specific immunostaining techniques. The loss of AR expression in peri-epithelial stroma as prostatic tissues de-differentiated correlated strongly with the depletion of WT-EGFR and with increasing expression of the EGFRvlII in the adjacent epithelium. In contrast, change s in epithelial AR immunopositivity in these tissues correlated weakly with the changes in normal and variant EGFR levels. This is the first report correlating the changes in the expression of these three proteins in archival material from the different human prostatic tissue histotypes. The loss of expression of proteins that contribute to the regulation of prostatic homeostasis (AR and WT-EGFR) correlates strongly with the expression of a constitutively active variant EGF rcceptor (EGFRvlII) in human prostate cancer. These changes occur at an early stage of neoplastic transformation and may contribute to the progression of the disease to hormone independence.