ANEUPLOIDY AND RAPID CELL-PROLIFERATION IN RECURRENT PROSTATE CANCERSWITH ANDROGEN RECEPTOR GENE AMPLIFICATION

Mechanisms of prostate cancer recurrence during androgen deprivation a re poorly understood. We recently described androgen receptor (AR) gen e amplification in 28% of recurrent prostate carcinomas from hormone-r efractory prostate cancer patients. To investigate the hypothesis that amplification of the AR gene promotes the growth of hormone-refractor y prostate carcinomas, DNA now cytometric (FCM) studies were carried o ut to compare matched, primary and hormone-refractory recurrent sample s from 31 prostate cancer patients. Recurrent tumours had a higher (P = 0.05) S-phase fraction (SPF) (10.6 +/- 4.6) than corresponding prima ry tumours from the same patients (7.0 +/- 4.1) and the frequency of a neuploidy also increased from 8-55%. Recurrent tumours with AR gene am plification had a significantly higher (P = 0.02) SPF (14.0 +/- 6.5) t han those with no amplification (9.0 +/- 2.9). The results suggest tha t clinical progression of prostate cancer during androgen withdrawal t herapy is often associated with increased cell proliferation rate and formation of DNA aneuploidy. AR amplification may be an important mole cular mechanism underlying the increase in proliferation rate of some recurrent tumours.