Aneuploidy and rapid cell proliferation in recurrent prostate cancers with androgen receptor gene amplification

Abstract

Mechanisms of prostate cancer recurrence during androgen deprivation are poorly understood. We recently described androgen receptor (AR) gene amplification in 28% of recurrent prostate carcinomas from hormone-refractory prostate cancer patients. To investigate the hypothesis that amplification of the AR gene promotes the growth of hormone-refractory prostate carcinomas, DNA flow cytometric (FCM) studies were carried out to compare matched, primary and hormone-refractory recurrent samples from 31 prostate cancer patients. Recurrent tumours had a higher (P=0.05) S-phase fraction (SPF) (10.6±4.6) than corresponding primary tumours from the same patients (7.0±4.1) and the frequency of aneuploidy also increased from 8–55%. Recurrent tumours with AR gene amplification had a significantly higher (P=0.02) SPF (14.0±6.5) than those with no amplification (9.0±2.9). The results suggest that clinical progression of prostate cancer during androgen withdrawal therapy is often associated with increased cell proliferation rate and formation of DNA aneuploidy. AR amplification may be an important molecular mechanism underlying the increase in proliferation rate of some recurrent tumours.