خبرگزاری آیصد (جدیدترین و جذاب ترین اخبار ایران و جهان)

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Urology news   14 Feb.2014

S Merson, Z H Yang, D Brewer, D Olmos, A Eichholz, F McCarthy, G Fisher, G Kovacs, D M Berney, C S Foster, H Møller, P Scardino, J Cuzick, C S Cooper, J P Clark and on behalf of the Transatlantic Prostate Group

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.

British Journal of Cancer , (30 January 2014) | doi:10.1038/bjc.2014.13