Amplification of the androgen receptor gene in bone metastases from hormone-refractory prostate cancer

R. S D Brown, J. Edwards, A. Dogan, H. Payne, S. J. Harland, J. M S Bartlett, J. R W Masters

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)237-244
Number of pages8
JournalJournal of Pathology
Volume198
Issue number2
DOIs
StatePublished - Oct 2002
Externally publishedYes

Fingerprint

Androgen Receptors
Prostatic Neoplasms
Hormones
Neoplasm Metastasis
Gene Amplification
Bone and Bones
X Chromosome
Genes
Fluorescence In Situ Hybridization
Neoplasms
Gene Dosage
Bone Marrow
Biopsy
Bone Neoplasms
Patient Selection
Androgens
Lymph Nodes
Recurrence

Keywords

  • Androgen receptor gene amplification
  • Aneusomy
  • Bone metastases
  • Fluorescence in situ hybridization
  • Hormone-refractory prostate cancer
  • X-chromosome

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Brown, R. S. D., Edwards, J., Dogan, A., Payne, H., Harland, S. J., Bartlett, J. M. S., & Masters, J. R. W. (2002). Amplification of the androgen receptor gene in bone metastases from hormone-refractory prostate cancer. Journal of Pathology, 198(2), 237-244. https://doi.org/10.1002/path.1206

Amplification of the androgen receptor gene in bone metastases from hormone-refractory prostate cancer. / Brown, R. S D; Edwards, J.; Dogan, A.; Payne, H.; Harland, S. J.; Bartlett, J. M S; Masters, J. R W.

In: Journal of Pathology, Vol. 198, No. 2, 10.2002, p. 237-244.

Research output: Contribution to journalArticle

Brown, RSD, Edwards, J, Dogan, A, Payne, H, Harland, SJ, Bartlett, JMS & Masters, JRW 2002, 'Amplification of the androgen receptor gene in bone metastases from hormone-refractory prostate cancer', Journal of Pathology, vol. 198, no. 2, pp. 237-244. https://doi.org/10.1002/path.1206
Brown, R. S D ; Edwards, J. ; Dogan, A. ; Payne, H. ; Harland, S. J. ; Bartlett, J. M S ; Masters, J. R W. / Amplification of the androgen receptor gene in bone metastases from hormone-refractory prostate cancer. In: Journal of Pathology. 2002 ; Vol. 198, No. 2. pp. 237-244.
@article{63cb8fff62f045aa95fec5eea58dffea,
title = "Amplification of the androgen receptor gene in bone metastases from hormone-refractory prostate cancer",
abstract = "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.",
keywords = "Androgen receptor gene amplification, Aneusomy, Bone metastases, Fluorescence in situ hybridization, Hormone-refractory prostate cancer, X-chromosome",
author = "Brown, {R. S D} and J. Edwards and A. Dogan and H. Payne and Harland, {S. J.} and Bartlett, {J. M S} and Masters, {J. R W}",
year = "2002",
month = "10",
doi = "10.1002/path.1206",
language = "English (US)",
volume = "198",
pages = "237--244",
journal = "Journal of Pathology",
issn = "0022-3417",
publisher = "John Wiley and Sons Ltd",
number = "2",

}

TY - JOUR

T1 - Amplification of the androgen receptor gene in bone metastases from hormone-refractory prostate cancer

AU - Brown, R. S D

AU - Edwards, J.

AU - Dogan, A.

AU - Payne, H.

AU - Harland, S. J.

AU - Bartlett, J. M S

AU - Masters, J. R W

PY - 2002/10

Y1 - 2002/10

N2 - 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.

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.

KW - Androgen receptor gene amplification

KW - Aneusomy

KW - Bone metastases

KW - Fluorescence in situ hybridization

KW - Hormone-refractory prostate cancer

KW - X-chromosome

UR - http://www.scopus.com/inward/record.url?scp=0036772932&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036772932&partnerID=8YFLogxK

U2 - 10.1002/path.1206

DO - 10.1002/path.1206

M3 - Article

C2 - 12237884

AN - SCOPUS:0036772932

VL - 198

SP - 237

EP - 244

JO - Journal of Pathology

JF - Journal of Pathology

SN - 0022-3417

IS - 2

ER -