Fibroblast growth factor-8 overexpression in prostate cancer predicts poor patient survival
Dorkin TJ., Robinson MC., Neal DE., Leung HY.
Introduction: Fibroblast growth factors (FGFs) have been implicated in the development of numerous malignancies including prostate cancer. Androgen-induced growth factor (FGF8) was first identified in the Shionogi mouse mammary carcinoma SC-3 cell line. The aim of this study was to determine whether FGF-8 was overexpressed in human prostate cancer and to correlate its expression with clinical data and outcome. Materials and methods: Samples from 106 cases of prostate cancer and 10 cases of BPH were examined. In situ hybridization was used to detect FGF-8 mRNA expression, using a specific digoxigenin-labelled antisense riboprobe. A sense riboprobe was used as a negative control for each sample. FGF-8 mRNA expression was assessed by two observers and the signals were graded as negative, weak, moderate or strong. Results: FGF-8 mRNA expression was identified within the malignant prostatic epithelium in 85 of 106 (80%) cases; homogeneous expression was observed in 73 of the 85 (86%) cases. Increased expression of FGF-8 mRNA correlated significantly with poorer histological grade (P < 0.001), higher Gleason score (P < 0.001) and advanced tumour stage (P = 0.0016). Men with tumours which expressed high levels of FGF-8 had worse survival rates than men with tumours which expressed no or low levels of FGF-8 (log-rank test. P= 0.034). FGF-8 mRNA was detected in a proportion of the basal cells within the prostatic epithelium of the BPH specimens. Conclusions: FGF-8 mRNA expression is upregulated in human prostate cancer and its expression correlates significantly with histological grade, Gleason score and tumour stage. Survival is significantly reduced in men with tumours which overexpress FGF-8 mRNA. © 1998 British Journal of Urology.