Relationship between antiandrogen withdrawal syndrome and genetic alterations of the androgen receptor in prostate cancer

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In patients with progressive prostate cancer who have been treated with maximum androgen blockade (MAB) by surgical or medical castration plus an antiandrogen, antiandrogen withdrawal can result in a significant decline in serum prostate-specific antigen (PSA) and, in some cases, it was associated with clinical response. This phenomenon was named as antiandrogen withdrawal syndrome. In 1997, we investigated relationship between clinical outcome and mutations of the androgen receptor gene. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) was carried out using prostate cancer tissue from untreated patients. No mutation was found in the androgen receptor gene of 17 cases irrespective of development of antiandrogen withdrawal syndrome. In 1998, the numbers of CAG and GGC repeats in the androgen receptor were examined in relation to antiandrogen withdrawal syndrome. Genomic DNA was extracted from prostate cancer tissue or peripheral blood and the numbers of CAG and GGC repeats were determined by PCR and polyacrylamide gel electrophoresis. The number of CAG repeat ranged 20-29 (mean : 22.3) in 7 of responders of endocrine therapy, 2 1-29 (mean : 24.2) in 5 of endocrine therapy-refractory patients who did not develop antiandrogen withdrawal syndrome, and 20-26 (mean : 22.5) in 6 of antiandrogen withdrawal syndrome cases, respectively. There was no close relationship between antiandrogen withdrawal syndrome and the number of CAG repeat of the androgen receptor gene. The number of GGC repeat was found to be 17 in most cases, and no significant difference was observed between the groups. Based on these results, at present it would be difficult to predict development of antiandrogen withdrawal syndrome by means of molecular biological examination of the androgen receptor gene.