Dept. of Medical Biology, UiT The Arctic University of Norway, Tromso, Norway.
Dept. of Clinical Medicine, UiT The Arctic University of Norway, Tromso, Norway.
Sci Rep. 2016 Sep 9;6:33114. doi: 10.1038/srep33114.
Androgens are considered important in normal prostate physiology and prostate cancer (PCa) pathogenesis. However, androgen-targeted treatment preventing PCa recurrence is still lacking. This indicates additional mediators contributing to cancer development. We sought to determine the prognostic significance of estrogen receptors, ERα and -β, and the aromatase enzyme in PCa. Tissue microarrays were created from 535 PCa patients treated with radical prostatectomy. Expression of ERα, ERβ and aromatase were evaluated using immunohistochemistry. Representative tumor epithelial (TE) and tumor stromal (TS) areas were investigated separately. Survival analyses were used to evaluate the markers correlation to PCa outcome. In univariate analyses, ERα in TS was associated with delayed time to clinical failure (CF) (p = 0.042) and PCa death (p = 0.019), while ERβ was associated with reduced time to biochemical failure (BF) (p = 0.002). Aromatase in TS and TE was associated with increased time to BF and CF respectively (p = 0.016, p = 0.046). Multivariate analyses supported these observations, indicating an independent prognostic impact of all markers. When stratifying the analysis according to different surgical centers the results were unchanged. In conclusion, significant prognostic roles of ERα, ERβ and aromatase were discovered in the in PCa specimens of our large multicenter cohort.
雄激素被认为在正常前列腺生理和前列腺癌（PCa）发病机制中起重要作用。然而，仍然缺乏针对雄激素的治疗方法来预防 PCa 的复发。这表明还有其他促进癌症发展的介质。我们试图确定雌激素受体 ERα 和 -β 以及芳香酶在 PCa 中的预后意义。从接受根治性前列腺切除术治疗的 535 名 PCa 患者中创建了组织微阵列。使用免疫组织化学评估 ERα、ERβ 和芳香酶的表达。分别研究了代表性的肿瘤上皮（TE）和肿瘤基质（TS）区域。生存分析用于评估标志物与 PCa 结局的相关性。在单因素分析中，TS 中的 ERα 与临床失败（CF）（p = 0.042）和 PCa 死亡（p = 0.019）的延迟时间相关，而 ERβ 与生化失败（BF）（p = 0.002）的时间减少相关。TS 和 TE 中的芳香酶与 BF 和 CF 的时间延长分别相关（p = 0.016，p = 0.046）。多因素分析支持这些观察结果，表明所有标志物均具有独立的预后影响。当根据不同的手术中心对分析进行分层时，结果保持不变。总之，在我们的大型多中心队列的 PCa 标本中发现了 ERα、ERβ 和芳香酶具有显著的预后作用。
