title: Amplification of the androgen receptor may not explain the development of androgen-independent prostate cancer.
abstract: 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.
authors.affiliation: University Department of Surgery, Glasgow Royal Infirmary, Glasgow, Scotland, UK. je10b@clinmed.gla.ac.uk
authors.forename: J
authors.initials: J
authors.lastname: Edwards
authors.forename: N S
authors.initials: NS
authors.lastname: Krishna
authors.forename: R
authors.initials: R
authors.lastname: Mukherjee
authors.forename: A D
authors.initials: AD
authors.lastname: Watters
authors.forename: M A
authors.initials: MA
authors.lastname: Underwood
authors.forename: J M
authors.initials: JM
authors.lastname: Bartlett
mesh_terms: 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
chemical_list: D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D011944:Receptors, Androgen; D017430:Prostate-Specific Antigen