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未经治疗的前列腺癌中雄激素受体基因拷贝数与蛋白表达

Androgen Receptor Gene Copy Number and Protein Expression in Treatment-Naïve Prostate Cancer.

作者信息

Poelaert Filip, Kumps Candy, Lumen Nicolaas, Verschuere Stephanie, Libbrecht Louis, Praet Marleen, Rottey Sylvie, Claeys Tom, Ost Piet, Decaestecker Karel, De Meerleer Gert, Van Praet Charles

机构信息

Department of Urology, Ghent University Hospital, Ghent, Belgium.

出版信息

Urol Int. 2017;99(2):222-228. doi: 10.1159/000455158. Epub 2017 Jan 5.

Abstract

OBJECTIVES

To evaluate the androgen receptor (AR) gene copy number in androgen deprivation therapy (ADT) treatment-naïve prostate cancer (PCa) patients and to evaluate the corresponding AR protein expression and assess the association between these features and prognostic factors.

MATERIALS AND METHODS

Chromosome X and AR gene copy number, using fluorescence-in-situ-hybridization, and epithelial-stromal AR expression, using AR immunohistochemistry, were analyzed in 62 ADT treatment-naïve PCa patients and 8 castration-refractory patients.

RESULTS

In ADT treatment-naïve PCa patients, the AR expression was higher in tumor epithelial cells versus surrounding stromal cells (p < 0.001) and versus normal epithelium in the same patient (p = 0.043). The difference between tumoral AR expression and expression in normal epithelium was higher in patients with ≥15% of tumor cells with increased AR copy number (p = 0.019). Peritumoral stroma had lower AR expression in patients with lymph-node or distant metastases compared to those without metastases (p = 0.038).

CONCLUSIONS

This research evaluates the link between AR gene status, expression profile, and possible prognostic factors. Furthermore, it highlights the importance of the peritumoral environment in PCa. Additional research is needed to further clarify the role of stromal AR in PCa dissemination and identify possible therapeutic strategies to target this mechanism.

摘要

目的

评估初治雄激素剥夺疗法(ADT)的前列腺癌(PCa)患者的雄激素受体(AR)基因拷贝数,评估相应的AR蛋白表达,并评估这些特征与预后因素之间的关联。

材料与方法

采用荧光原位杂交技术分析62例初治ADT的PCa患者和8例去势抵抗患者的X染色体和AR基因拷贝数,采用AR免疫组织化学分析上皮-间质AR表达。

结果

在初治ADT的PCa患者中,肿瘤上皮细胞中的AR表达高于周围基质细胞(p<0.001),且高于同一患者的正常上皮细胞(p=0.043)。AR拷贝数增加的肿瘤细胞≥15%的患者,肿瘤AR表达与正常上皮表达之间的差异更大(p=0.019)。与无转移的患者相比,有淋巴结或远处转移的患者瘤周基质的AR表达较低(p=0.038)。

结论

本研究评估了AR基因状态、表达谱与可能的预后因素之间的联系。此外,它突出了瘤周环境在PCa中的重要性。需要进一步的研究来进一步阐明基质AR在PCa播散中的作用,并确定针对这一机制的可能治疗策略。

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