Amplification of the androgen receptor may not explain the development of androgen-independent prostate cancer.
OBJECTIVE
To examine the role of androgen receptor (AR) gene amplification and aneusomy of the X chromosome in the development of antiandrogen-resistant prostate cancer.


METHODS
Twenty patients with prostate cancer resistant to androgen-deprivation therapy were selected for study. The records of patients with tumours before and after antiandrogen therapy, and with a full clinical follow-up, were retrieved. AR gene amplification and X chromosome copy number were assessed by fluorescence in situ hybridization using a labelled probe at locus Xq11-13 for the AR gene and a labelled alpha-satellite probe for the X chromosome. At least 20 nuclei were scored over three tumour areas by two independent observers.


RESULTS
Aneusomy of the X chromosome was reported respectively in seven (35%) and 11 (55%) tumours before and after hormone relapse, the AR gene copy number was increased in seven (35%) and 13 (65%), respectively, and AR gene amplification was detected in one (5%) and three (15%), respectively. Neither increased AR copy number nor AR amplification in primary tumours precluded a biological response to androgen-deprivation therapy.


CONCLUSIONS
The rate of AR gene amplification is too low to be solely responsible for the development of antiandrogen-resistant prostate cancer. Also, the presence of amplified AR and cells aneusomic for the X chromosome in primary tumours that respond to androgen-deprivation therapy suggests that an increase in AR gene copy number does not prevent a tumour from responding to this therapy. Therefore other mechanisms which could cause hormone-refractory prostate cancer must be investigated before it is understood why so many patients relapse with this disease.
Edwards
J
J
University Department of Surgery, Glasgow Royal Infirmary, Glasgow, Scotland, UK. je10b@clinmed.gla.ac.uk
Krishna
N S
NS
Mukherjee
R
R
Watters
A D
AD
Underwood
M A
MA
Bartlett
J M
JM
D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D005784:Gene Amplification / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D011944:Receptors, Androgen / Q000235:genetics*; D012189:Retrospective Studies; D014960:X Chromosome / Q000235:genetics
D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D011944:Receptors, Androgen; D017430:Prostate-Specific Antigen