Comparing the expression profiles of steroid hormone receptors and stromal cell markers in prostate cancer at different Gleason scores.
Comparing the expression profiles of steroid hormone receptors and stromal cell markers in prostate cancer at different Gleason scores.
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DOI：
10.1038/s41598-018-32711-9
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发表时间：
2018-09-25
影响因子：
4.6
通讯作者：
Joniau S
中科院分区：
文献类型：
--
作者：
Gevaert T;Van Eycke YR;Vanden Broeck T;Van Poppel H;Salmon I;Rorive S;Claessens F;De Ridder D;Decaestecker C;Joniau S
抗血管生成药物和免疫调节药物的研究进展表明，肿瘤微环境在肿瘤研究中的地位日益重要。在这里，我们通过比较不同的Gleason评分(GS)和TME的类固醇激素受体、肿瘤激活的成纤维细胞(CAF)标志物和血管密度的组织表达谱来研究GS与TME的相关性。因此，匹配的患者队列由不同的GS(6-7-8)组成。每个患者6个样本的组织微阵列进行免疫组织化学处理。染色的幻灯片被数字化，间质和上皮被选择性地注释，所有选定的区域都被定量分析标记表达。最引人注目的发现是，与低GS前列腺癌和配对的前列腺癌非肿瘤组织相比，高GS前列腺癌的几种类固醇激素受体间质表达水平降低，CAF表型增加，血管密度增加。目前的数据揭示了前列腺癌分化和TME成分之间的复杂关系，并提示不同的GS可能与TME中不同的可能的作用靶点相关。标准化数字图像分析工具的使用产生了稳健和可重现的定量数据，与免疫组织化学的经典半定量和依赖于观察者的视觉评分相比，这是新的和更多的信息。
The recent developments in anti-angiogenic and immunomodulatory drugs show that the tumour micro-environment (TME) becomes increasingly important in cancer research. Here we investigated the correlation between the Gleason score (GS) and the TME by comparing tissue expression profiles of steroid hormone receptors, cancer activated fibroblast (CAF) markers and vessel densities between different GS groups. Therefore, matched patient cohorts were composed for different GS (6-7-8). Tissue micro-arrays with 6 samples/patient were processed for immunohistochemistry. Stained slides were digitised, stroma and epithelium were selectively annotated, and all selected areas were quantitatively analysed for marker expression. The most striking findings were decreased stromal expression levels of several steroid hormone receptors, increased CAF-phenotypes and increased vessel densities in high GS prostate cancer compared to low GS prostate cancer and paired prostate non-tumour tissue. The present data reveal a complex correlation between prostate cancer differentiation and TME components and suggest that different GS can be associated with different possible actionable targets in the TME. The use of standardised digital image analysis tools generated robust and reproducible quantitative data, which is novel and more informative compared to the classic semi-quantitative and observer-dependent visual scoring of immunohistochemistry.
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影响因子：
5.6
作者：
Epstein, Jonathan I.;Amin, Mahul B.;Humphrey, Peter A.
通讯作者：
Humphrey, Peter A.
影响因子：
3.5
作者：
El-Gohary, Yasser M.;Silverman, Jan F.;Saad, Reda S.
通讯作者：
Saad, Reda S.
影响因子：
4.5
作者：
Mathieu, Romain;Klatte, Tobias;Shariat, Shahrokh F.
通讯作者：
Shariat, Shahrokh F.
影响因子：
4.1
作者：
Nelson AW;Groen AJ;Miller JL;Warren AY;Holmes KA;Tarulli GA;Tilley WD;Katzenellenbogen BS;Hawse JR;Gnanapragasam VJ;Carroll JS
通讯作者：
Carroll JS
影响因子：
3.7
作者：
Hammarsten P;Dahl Scherdin T;Hägglöf C;Andersson P;Wikström P;Stattin P;Egevad L;Granfors T;Bergh A
通讯作者：
Bergh A