Service d'Urologie, Centre Hospitalier Universitaire-Université de Poitiers, Poitiers, France.
J Urol. 2010 Nov;184(5):2172-8. doi: 10.1016/j.juro.2010.06.089. Epub 2010 Sep 17.
Despite increasing evidence that estrogen signaling has a key role in prostate cancer development and progression, few studies have focused on the estrogen pathway in the transition from hormone sensitive to hormone refractory tumors. We investigated the expression of proteins related to androgen and estrogen metabolism in paired prostate cancer samples collected before androgen deprivation therapy and after hormonal relapse.
The study included 55 patients treated for prostate cancer only with androgen deprivation therapy and in whom tissue was available before treatment induction and after recurrence. Immunohistochemistry was performed using tissue microarray with antibodies directed against androgen receptor, phosphorylated androgen receptor, estrogen receptor α, estrogen receptor β, 5α-reductase 1 and 2, aromatase, BCAR1 and the proliferation marker Ki67.
Compared to hormone sensitive samples, tissues collected after hormonal relapse were characterized by increased expression of Ki67, androgen receptor, phosphorylated androgen receptor (p <0.001) and BCAR (p = 0.03), and by lower staining for 5α-reductase 2 (p = 0.002), estrogen receptor β (p = 0.016) and aromatase (p <0.001). Shorter time to hormonal relapse was associated with high expression of aromatase and BCAR1 on diagnostic biopsy, together with low staining for estrogen receptor α in stromal cells. Overall survival was significantly shorter when tissues collected after relapse showed a high proliferation index and low estrogen receptor α expression.
Results revealed dysregulation of proteins involved in androgen pathways, and in estrogen synthesis and signaling during the development of hormone refractory prostate cancer.
尽管越来越多的证据表明雌激素信号在前列腺癌的发展和进展中起着关键作用，但很少有研究关注从激素敏感到激素抵抗肿瘤的过程中雌激素途径。我们研究了在雄激素剥夺治疗前和激素复发后收集的配对前列腺癌样本中与雄激素和雌激素代谢相关的蛋白质的表达。
该研究包括 55 名仅接受雄激素剥夺治疗的前列腺癌患者，在治疗诱导前和复发后有组织可用。使用针对雄激素受体、磷酸化雄激素受体、雌激素受体 α、雌激素受体 β、5α-还原酶 1 和 2、芳香酶、BCAR1 和增殖标志物 Ki67 的组织微阵列进行免疫组织化学染色。
与激素敏感样本相比，激素复发后采集的组织表现为 Ki67、雄激素受体、磷酸化雄激素受体（p<0.001）和 BCAR（p=0.03）表达增加，而 5α-还原酶 2（p=0.002）、雌激素受体β（p=0.016）和芳香酶（p<0.001）染色减少。激素复发时间较短与诊断性活检中芳香酶和 BCAR1 高表达以及基质细胞中雌激素受体 α 染色减少有关。当复发后采集的组织显示高增殖指数和低雌激素受体 α 表达时，总生存时间明显缩短。
结果表明，在激素抵抗性前列腺癌的发展过程中，雄激素途径以及雌激素合成和信号转导中的蛋白质发生失调。
