Palmberg C, Koivisto P, Kakkola L, Tammela T L, Kallioniemi O P, Visakorpi T
Division of Urology, Tampere University Hospital, Finland.
J Urol. 2000 Dec;164(6):1992-5.
Amplification of the androgen receptor gene has been found in a third of hormone refractory prostate carcinomas. It is possible that amplification facilitates cell growth ability in low concentrations of androgens remaining in the serum after androgen deprivation therapy. We evaluate whether androgen receptor gene amplification at primary progression is associated with response to second line combined androgen blockade for prostate cancer.
A total of 77 patients with prostate cancer were treated initially with androgen deprivation monotherapy followed by combined androgen blockade after the first progression. After initiation of second line combined androgen blockade patients were followed every 3 months to evaluate treatment responses. Biopsies were taken from the prostate at the first progression under endocrine monotherapy. Androgen receptor gene copy number was determined by fluorescence in situ hybridization.
Androgen receptor gene amplification was found in 10 of the 77 cases (13%) at the primary disease progression, and was associated with a favorable response to second line combined androgen blockade. Only 1 of 34 (3%) patients classified as nonresponders had androgen receptor gene amplification, whereas 9 of 41 (21%) classified as having either stable disease or response had amplification (p = 0.016). Patients with androgen receptor gene amplification also had a decrease in prostate specific antigen more often after combined androgen blockade than those with no amplification (p = 0.079). However, androgen receptor gene amplification was not associated with patient survival after the first progression.
Androgen receptor gene amplification detected in tumors progressing during androgen deprivation monotherapy is associated with favorable treatment response to second line combined androgen blockade. This finding suggests that at least some androgen receptor amplified tumors retain a high degree of dependency on residual androgens remaining in serum after monotherapy.
在三分之一的激素难治性前列腺癌中发现了雄激素受体基因扩增。雄激素剥夺治疗后血清中残留的低浓度雄激素可能促进细胞生长，而基因扩增可能发挥了这一作用。我们评估原发性进展时雄激素受体基因扩增是否与前列腺癌二线联合雄激素阻断治疗的反应相关。
共有77例前列腺癌患者最初接受雄激素剥夺单一疗法治疗，首次进展后接受联合雄激素阻断治疗。开始二线联合雄激素阻断治疗后，每3个月对患者进行随访以评估治疗反应。在内分泌单一疗法治疗首次进展时从前列腺取活检组织。通过荧光原位杂交测定雄激素受体基因拷贝数。
在77例患者中的10例（13%）原发性疾病进展时发现雄激素受体基因扩增，且与二线联合雄激素阻断治疗的良好反应相关。在34例（3%）被归类为无反应者中只有1例有雄激素受体基因扩增，而在41例被归类为病情稳定或有反应者中有9例（21%）有扩增（p = 0.016）。与无扩增者相比，雄激素受体基因扩增患者在联合雄激素阻断治疗后更常出现前列腺特异性抗原下降（p = 0.079）。然而，雄激素受体基因扩增与首次进展后的患者生存率无关。
在雄激素剥夺单一疗法治疗期间进展的肿瘤中检测到的雄激素受体基因扩增与二线联合雄激素阻断治疗的良好反应相关。这一发现表明，至少一些雄激素受体扩增的肿瘤对单一疗法后血清中残留的雄激素仍高度依赖。
