FGF8 over-expression in prostate cancer is associated with decreased patient survival and persists in androgen independent disease

Identification of prostate cancers at high risk of progression is difficult and a better understanding of how peptide growth factors influence cellula r function might be useful. Fibroblast growth factors (FGFs) have been impl icated in prostate cancer development. FGF8 was identified in the Shionogi mouse mammary carcinoma SC-3 cell line as an androgen-induced mitogen. We t ested if FGF8 was over-expressed in human prostate cancer and if its expres sion correlated with clinical data and outcome. One hundred and six cases o f prostate cancer and ten cases of BPH were examined. In situ hybridization was employed to detect FGF8 mRNA expression, which,vas identified within t he malignant prostatic epithelium in 85/106 (80.2%) cases, Increased expres sion of FGF8 correlated significantly with higher Gleason scores (P=0.0004) and advanced tumour stage (P=0.0016), Using immunohistochemistry, me confi rmed over-expression of the FGF8b isoform, Men with tumours which expressed high levels of FGF8 had worse survival (P=0.034), although FGF8 mRNA was n ot able to provide additional prognostic information in a multivariate anal ysis. Additionally, FGF8 expression was shown to persist in androgen indepe ndent prostate cancer. Using a range of normal adult tissues, FGF8 expressi on was restricted to neurones and the germinal epithelium in addition to th e prostate, in vitro studies demonstrated that in the presence of neutraliz ing antibody to FGF8b there was significant inhibition of prostate cancer c ell growth, confirming the biological significance of FGF8 in prostate carc inogenesis.