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

• Published in: The Journal of pathology Vol. 189; no. 2; pp. 219 - 223
• Main Authors: Koivisto, Pasi A., Helin, Heikki J.
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.10.1999; Wiley
• Subjects: androgen receptor gene; androgen regulation; Biological and medical sciences; Biomarkers, Tumor - metabolism; Gene Amplification; hormonal therapy; hormone refractory; Humans; Immunoenzyme Techniques; In Situ Hybridization, Fluorescence; Male; Medical sciences; Neoplasm Recurrence, Local - genetics; Neoplasm Recurrence, Local - metabolism; Neoplasm Recurrence, Local - therapy; Nephrology. Urinary tract diseases; prostate-specific antigen; Prostate-Specific Antigen - metabolism; Prostatic Neoplasms - genetics; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - therapy; Receptors, Androgen - genetics; Treatment Failure; Tumors of the urinary system; Urinary tract. Prostate gland; Adenocarcinoma; Human; Immunohistochemistry; Deprivation; Urinary system disease; Prostate disease; Androgen; Male; Malignant tumor; Prostate specific antigen; Pathology; Gene amplification; Fluorescence in situ hybridization; Molecular biology; Sex steroid hormone; Male genital diseases; Prostate; Negative therapeutic reaction; Hormonal receptor
• ISSN: 0022-3417; 1096-9896
• DOI: 10.1002/(SICI)1096-9896(199910)189:2<219::AID-PATH423>3.0.CO;2-F

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. Copyright © 1999 John Wiley & Sons, Ltd.