Todenhöfer Tilman, Park Emily Sunyong, Duffy Simon, Deng Xiaoyan, Jin Chao, Abdi Hamidreza, Ma Hongshen, Black Peter C
Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada; Department of Urology, University Hospital, Tübingen, Germany.
Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada; Department of Mechanical Engineering, University of British Columbia, Vancouver, Canada.
Urol Oncol. 2016 Nov;34(11):483.e9-483.e16. doi: 10.1016/j.urolonc.2016.06.004. Epub 2016 Sep 19.
Circulating tumor cells (CTC) have become an important tool in the monitoring of patients with advanced prostate cancer (PC). The role of CTC in localized disease has been addressed by only few studies. However, results of CTC analyses are strongly dependent on the platform used for CTC enrichment and detection. In the present study, a microfluidic platform allowing for antigen-independent enrichment of CTC was investigated for its ability to detect CTC in patients with clinically localized PC.
Blood (2ml) was collected preoperatively from 50 consecutive patients undergoing radical prostatectomy for clinically localized PC. CTC were enriched using a microfluidic ratchet mechanism allowing separation of CTC from white blood cells based on differences in size and deformability. Enriched cells were stained for immunofluorescence with antibodies targeting pancytokeratin, epithelial cell adhesion molecule, and CD45. In 21 patients, we performed staining for the androgen receptor. CTC counts were correlated with clinical and pathological parameters using the Wilcoxon-Mann-Whitney test for continuous parameters and Chi-square test for categorical parameters.
CTC were detected in 25 (50%) patients. The median number of CTC in CTC-positive patients was 9 CTC/2ml (range: 1-417). Pancytokeratin positive CTC showed expression of androgen the receptor. We observed no correlation between CTC counts and prostate-specific antigen concentration, tumor stage, lymph node stage, or Gleason grade.
In a representative cohort of patients with clinically localized PC, CTC can be detected in a considerable proportion of patients when using a new microfluidic ratchet mechanism. This encourages further studies assessing the prognostic effect of antigen-independent enriched CTC in patients with PC.
循环肿瘤细胞(CTC)已成为晚期前列腺癌(PC)患者监测的重要工具。仅有少数研究探讨了CTC在局限性疾病中的作用。然而,CTC分析结果强烈依赖于用于CTC富集和检测的平台。在本研究中,对一种允许非抗原依赖性富集CTC的微流控平台进行了研究,以评估其检测临床局限性PC患者中CTC的能力。
对50例因临床局限性PC接受根治性前列腺切除术的连续患者术前采集2ml血液。使用微流控棘轮机制富集CTC,该机制可根据大小和可变形性差异将CTC与白细胞分离。对富集的细胞用靶向全细胞角蛋白、上皮细胞粘附分子和CD45的抗体进行免疫荧光染色。在21例患者中,我们进行了雄激素受体染色。使用Wilcoxon-Mann-Whitney检验分析连续参数、卡方检验分析分类参数,将CTC计数与临床和病理参数进行相关性分析。
25例(50%)患者检测到CTC。CTC阳性患者的CTC中位数为9个/2ml(范围:1 - 417)。全细胞角蛋白阳性的CTC显示出雄激素受体表达。我们未观察到CTC计数与前列腺特异性抗原浓度、肿瘤分期、淋巴结分期或Gleason分级之间存在相关性。
在具有代表性的临床局限性PC患者队列中,使用新型微流控棘轮机制时,相当一部分患者可检测到CTC。这鼓励进一步开展研究,评估非抗原依赖性富集的CTC对PC患者的预后影响。