期刊
BRITISH JOURNAL OF CANCER
卷 110, 期 6, 页码 1655-1662出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/bjc.2014.13
关键词
androgen receptor gene amplification; FISH; hormone naive; prostate cancer prognosis
类别
资金
- International Association of Cancer research
- Bob Champion Cancer Trust
- Grand Charity of Freemasons
- Big C Cancer Charity
- Orchid and Prostate Cancer UK
Background: Androgen receptor (AR)-gene amplification, found in 20-30% of castration-resistant prostate cancer (CRPCa) is proposed to develop as a consequence of hormone-deprivation therapy and be a prime cause of treatment failure. Here we investigate AR-gene amplification in cancers before hormone deprivation therapy. Methods: A tissue microarray (TMA) series of 596 hormone-naive prostate cancers (HNPCas) was screened for chromosome X and AR-gene locus-specific copy number alterations using four-colour fluorescence in situ hybridisation. Results: Both high level gain in chromosome X (>= 4 fold; n =4, 0.7%) and locus-specific amplification of the AR-gene (n =6, 1%) were detected at low frequencies in HNPCa TMAs. Fluorescence in situ hybridisation mapping whole sections taken from the original HNPCa specimen blocks demonstrated that AR-gene amplifications exist in small foci of cells (<= 600 nm, <= 1% of tumour volume). Patients with AR gene-locus-specific copy number gains had poorer prostate cancer-specific survival. Conclusion: Small clonal foci of cancer containing high level gain of the androgen receptor (AR)-gene develop before hormone deprivation therapy. Their small size makes detection by TMA inefficient and suggests a higher prevalence than that reported herein. It is hypothesised that a large proportion of AR-amplified CRPCa could pre-date hormone deprivation therapy and that these patients would potentially benefit from early total androgen ablation.
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