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循环肿瘤细胞的免疫磁珠定量分析作为激素初治转移性前列腺癌患者雄激素剥夺反应性的预后因素

Immunomagnetic quantification of circulating tumor cells as a prognostic factor of androgen deprivation responsiveness in patients with hormone naive metastatic prostate cancer.

作者信息

Okegawa Takatsugu, Nutahara Kikuo, Higashihara Eiji

机构信息

Department of Urology, The University of Kyorin, Mitaka, Tokyo, Japan.

出版信息

J Urol. 2008 Oct;180(4):1342-7. doi: 10.1016/j.juro.2008.06.021. Epub 2008 Aug 15.

DOI:10.1016/j.juro.2008.06.021
PMID:18707699
Abstract

PURPOSE

We determined whether circulating tumor cells predict prostate specific antigen failure in patients with metastatic prostate cancer before endocrine therapy and compared their prognostic ability with other clinical factors.

MATERIALS AND METHODS

Circulating tumor cells were enumerated with the CellSearchtrade mark system in whole blood. This system was developed using epithelial cell adhesion molecule antibody based immunomagnetic capture and automated staining methodology. Prostate cancer cell lines (PC3, LNCaP, DU145) and mixed blood from healthy men were analyzed using this system. Blood samples from 80 patients with metastatic prostate cancer before endocrine therapy were analyzed. Circulating tumor cells were then assessed every 3 months after endocrine therapy in these patients.

RESULTS

Circulating tumor cell assay accuracy and reliability were determined using prostate cancer cell line (PC3, LNCaP, DU145) spiking experiments, which demonstrated a strong linear correlation (r = 0.99) and a constant recovery rate of 69% +/- 3%, 95% +/- 3% and 89% +/- 2%, respectively. The number of circulating tumor cells found ranged from 0 to 222 per 7.5 ml blood (mean 17 +/- 31, median 14). A threshold of 5 or more circulating tumor cells per 7.5 ml blood was used to evaluate the ability of circulating tumor cells to predict androgen deprivation responsiveness. Of the 80 patients 44 (55%) had 5 or more circulating tumor cells with a median androgen deprivation responsiveness of 17 months compared to more than 32 months for those with fewer than 5 circulating tumor cells (p = 0.007). The presence of circulating tumor cells, nadir prostate specific antigen values and Gleason score were significant parameters predictive of androgen deprivation responsiveness on univariate and multivariate analyses.

CONCLUSIONS

In this study the presence of 5 or more circulating tumor cells in 7.5 ml blood was associated with androgen deprivation responsiveness in patients with metastatic prostate cancer before endocrine therapy.

摘要

目的

我们确定循环肿瘤细胞是否能预测转移性前列腺癌患者内分泌治疗前前列腺特异性抗原失败,并将其预后能力与其他临床因素进行比较。

材料与方法

使用CellSearch商标系统对全血中的循环肿瘤细胞进行计数。该系统采用基于上皮细胞粘附分子抗体的免疫磁捕获和自动染色方法开发。使用该系统分析前列腺癌细胞系(PC3、LNCaP、DU145)和健康男性的混合血液。对80例内分泌治疗前的转移性前列腺癌患者的血样进行分析。然后在这些患者内分泌治疗后每3个月评估一次循环肿瘤细胞。

结果

通过前列腺癌细胞系(PC3、LNCaP、DU145)加样实验确定了循环肿瘤细胞检测的准确性和可靠性,实验显示出强线性相关性(r = 0.99),回收率分别恒定为69%±3%、95%±3%和89%±2%。每7.5 ml血液中发现的循环肿瘤细胞数量范围为0至222个(平均17±31个,中位数14个)。每7.5 ml血液中5个或更多循环肿瘤细胞的阈值用于评估循环肿瘤细胞预测雄激素剥夺反应性的能力。80例患者中,44例(55%)有5个或更多循环肿瘤细胞,其雄激素剥夺反应性的中位数为17个月,而循环肿瘤细胞少于5个的患者则超过32个月(p = 0.007)。在单变量和多变量分析中,循环肿瘤细胞的存在、最低前列腺特异性抗原值和 Gleason评分是预测雄激素剥夺反应性的重要参数。

结论

在本研究中,7.5 ml血液中存在5个或更多循环肿瘤细胞与内分泌治疗前转移性前列腺癌患者的雄激素剥夺反应性相关。

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