Objective: We recently found amplification of the androgen receptor (AR) gene in approximately 30% of locally recurrent prostate carcinomas from patients treated by conventional androgen deprivation (castration) therapy, whereas none of the untreated primary prostate tumors showed this amplification. This suggests that AR gene amplification was selected during androgen deprivation therapy. The present case study represents our initial approach to evaluate the role that AR amplification may play in therapy resistance after other forms of endocrine therapy.
Material and methods: Specimens from both a primary and a subsequent locally recurrent tumor were studied for amplification of the AR gene by fluorescence in situ hybridization from a prostate cancer patient who experienced tumor progression after monotherapy with the potent antiandrogen bicalutamide (Casodex, a trade mark, the property of Zeneca Ltd).
Results and conclusions: High-level amplification of the AR gene was found in the recurrent tumor, whereas no evidence of amplification was found in the primary tumor. After recurrence, the patient first received chemotherapy (ifosfamide) for 15 weeks with no response, followed by maximal androgen blockade (MAB). The latter therapy resulted in a favorable short-term response. This case study has the following implications which warrant further research: (1) AR amplification may be selected not only by castration but also by therapy with a competitive peripheral androgen-receptor-blocking agent, and (2) recurrent tumors with AR amplification may be particularly likely to benefit from MAB as a second-line therapy.