Androgen receptor gene amplification increases tissue PSA protein expression in hormone-refractory prostate carcinoma

Abstract

Androgen receptor (AR) gene amplification was analysed by fluorescence in situ hybridization (FISH) from 24 paraffin-embedded prostate carcinoma samples recurring locally during hormonal therapy and prostate-specific antigen (PSA) expression from 15/24 of these samples was studied by immunohistochemistry (IHC). AR gene amplification was detected in 29 per cent (7/24) of the recurrent tumours. Using modified Histoscore (MHS), PSA immunostaining in the AR gene-amplified tumours (133+/-102) was twice as high (p=0.054) as in tumours with no amplification (66+/-79) and a statistically significant (p=0.026) association between AR gene amplification and PSA positivity was found when MHS>/=20 was considered positive for PSA. AR gene copy number was positively correlated with PSA MHS in the AR gene-amplified tumours (r=0.893, p=0.012). Histological grade, Gleason's score, and tumour stage did not differ significantly between patients with and without AR gene amplification. In conclusion, these results indicate that AR gene amplification leads to up-regulation of PSA gene (and possibly other androgen-dependent genes), and that patients with AR gene amplification may have elevated serum PSA concentrations without a clear correlation with actual tumour burden.