Gain of androgen receptor gene copies in primary prostate cancer due to X chromosome polysomy

Abstract

Background: Prostate cancer is an androgen dependent tumor. In advanced prostate cancers androgen deprivation has proved to be an effective therapy, but 25% show no response. In this study prostatectomy specimens from patients without preoperative therapy were analyzed to determine the possible mechanism of primary antiandrogen resistance.

Methods: The number of androgen receptor (AR) gene copies and X-centromeres were investigated from 80 prostate cancer specimens by FISH analysis.

Results: In 9 out of 80 prostate cancers additional X-chromosomes with the corresponding AR gene could be detected. Polysomy of the X-chromosome correlates with pathological classification and tumor volume.

Conclusions: Additional AR genes due to polysomy of the X-chromosome are present in a subgroup of primary prostate cancers prior to antiandrogen therapy. Because the growth of prostate cancers is androgen dependent, these specimens may have an advantage in low concentrations of androgens. This may be a factor for initial antiandrogen resistance.