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

在接受最大雄激素阻断(MAB)的进展期前列腺癌患者中，通过手术或药物去势加抗雄激素治疗，抗雄激素撤除可导致血清前列腺特异性抗原(PSA)显著下降，在某些情况下，这与临床反应有关。这一现象被称为抗雄激素戒断综合征。1997年，我们调查了雄激素受体基因突变与临床结果之间的关系。对未经治疗的前列腺癌组织进行聚合酶链式反应-单链构象多态性分析(PCR-SSCP)。17例患者中未发现雄激素受体基因突变，与抗雄激素戒断综合征的发生无关。1998年，研究了雄激素受体中CAG和GGC重复数与抗雄激素戒断综合征的关系。从前列腺癌组织或外周血中提取基因组DNA，用聚合酶链式反应和聚丙烯酰胺凝胶电泳法检测CAG和GGC重复数。7例内分泌治疗有效者CAG重复数为20~29次(平均22.3次)，5例内分泌治疗难治者CAG重复数为21~29次(平均24.2次)，6例抗雄激素戒断综合征患者CAG重复数为20~26次(平均22.5次)。抗雄激素戒断综合征与雄激素受体基因CAG重复数无密切关系。多数病例GGC重复数为17个，组间差异无统计学意义。基于这些结果，目前很难通过雄激素受体基因的分子生物学检测来预测抗雄激素戒断综合征的发展。

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.