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

Androgen receptor (AR) gene amplification was analysed by fluorescence in s itu hybridization (FISH) from 24 paraffin-embedded prostate carcinoma sampl es recurring locally during hormonal therapy and prostate-specific antigen (PSA) expression from 15/24 of these samples was studied by immunohistochem istry (IHC). AR gene amplification was detected in 29 per cent (7/24) of th e recurrent tumours, Using modified Histoscore (MHS), PSA immunostaining in the AR gene-amplified rumours (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 greater than or equal to 20 was considered positive for PSA , AR gene copy number was positively correlated with PSA MHS in the AR gene -amplified rumours (r=0.893, p=0.012). Histological grade, Gleason's score, and tumour stage did not differ significantly between patients with and wi thout AR gene amplification. In conclusion, these results indicate that AR gene amplification leads to up-regulation of PSA gene (and possibly other a ndrogen-dependent genes), and that patients with AR gene amplification may have elevated serum PSA concentrations without a clear correlation with act ual tumour burden, Copyright (C) 1999 John Whey & Sons, Ltd.