PMID- 12237884
OWN - NLM
STAT- MEDLINE
DCOM- 20030106
LR  - 20220519
IS  - 0022-3417 (Print)
IS  - 0022-3417 (Linking)
VI  - 198
IP  - 2
DP  - 2002 Oct
TI  - Amplification of the androgen receptor gene in bone metastases from 
      hormone-refractory prostate cancer.
PG  - 237-44
AB  - The aim of this study was to examine the prevalence of androgen receptor (AR) 
      amplification in metastases to bone and other sites in patients with 
      hormone-refractory prostate cancer (HRPC) and to compare these findings with 
      those in pretreatment primary tumour samples from the same patients. Tissue from 
      24 patients with HRPC was available for study, together with 13 primary tumour 
      specimens. AR gene amplification and copy number for X-chromosome were assessed 
      by fluorescence in situ hybridization (FISH) using a SpectrumOrange-labelled 
      probe at locus Xq11-13 for the AR gene and a SpectrumGreen-labelled 
      alpha-satellite probe for the X-chromosome (Vysis, UK, Ltd.). A minimum of 20 
      nuclei were scored in each of three tumour areas by two independent observers. 
      Samples from 18/24 patients with HRPC (12 bone marrow biopsies, three local 
      tumour recurrences, and three lymph nodes) and nine primary tumour specimens were 
      adequate for FISH analysis. Results were expressed as a mean ratio of AR gene 
      copy number : mean X-chromosome number, with a ratio of greater than 1.5 defined 
      as amplification. AR gene amplification was seen in 9/18 (50%) cases of HRPC and 
      in none of the primary (untreated) tumour specimens (p = 0.0048, Fisher's exact 
      test). For the 12 bone marrow samples, AR gene amplification occurred in 5/12 
      (38%) cases. Elevated copy number for chromosome X occurred in 3/18 (17%) HRPC 
      and 4/9 (44%) matched primary tumours. This study shows for the first time that 
      AR gene amplification can be demonstrated by FISH in bone metastases from HRPC 
      patients. Because bone marrow biopsies can be obtained from most patients with 
      HRPC, the findings provide a rational basis for the routine selection of patients 
      who may respond more favourably to second-line anti-androgen therapy.
CI  - Copyright 2002 John Wiley & Sons, Ltd.
FAU - Brown, R S D
AU  - Brown RS
AD  - The Prostate Cancer Research Centre, Third Floor, Charles Bell House, 67 Riding 
      House Street, London W1W 7EY, UK. rsdbrown@mac.com
FAU - Edwards, J
AU  - Edwards J
FAU - Dogan, A
AU  - Dogan A
FAU - Payne, H
AU  - Payne H
FAU - Harland, S J
AU  - Harland SJ
FAU - Bartlett, J M S
AU  - Bartlett JM
FAU - Masters, J R W
AU  - Masters JR
LA  - eng
PT  - Journal Article
PL  - England
TA  - J Pathol
JT  - The Journal of pathology
JID - 0204634
RN  - 0 (Antineoplastic Agents, Hormonal)
RN  - 0 (Receptors, Androgen)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Agents, Hormonal/therapeutic use
MH  - Bone Marrow/pathology
MH  - Bone Neoplasms/*genetics/*secondary
MH  - Chromosomes, Human, X
MH  - Drug Resistance, Neoplasm
MH  - *Gene Amplification
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Middle Aged
MH  - Observer Variation
MH  - Patient Selection
MH  - Prostatic Neoplasms/drug therapy/*genetics
MH  - Receptors, Androgen/*genetics
EDAT- 2002/09/19 10:00
MHDA- 2003/01/08 04:00
CRDT- 2002/09/19 10:00
PHST- 2002/09/19 10:00 [pubmed]
PHST- 2003/01/08 04:00 [medline]
PHST- 2002/09/19 10:00 [entrez]
AID - 10.1002/path.1206 [doi]
PST - ppublish
SO  - J Pathol. 2002 Oct;198(2):237-44. doi: 10.1002/path.1206.