All circulating EpCAM+CK+CD45-objects predict overall survival in castration-resistant prostate cancer

All circulating EpCAM+CK+CD45-objects predict overall survival in castration-resistant prostate cancer
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DOI:
10.1093/annonc/mdq030
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发表时间:
2010-09-01
期刊:
影响因子:
50.5
通讯作者:
Terstappen, L. W. M. M.
Terstappen, L. W. M. M.
中科院分区:
医学1区
文献类型:
--
作者:
Coumans, F. A. W.;Doggen, C. J. M.;Terstappen, L. W. M. M.

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背景:转移性癌患者中存在 5 个或更多循环肿瘤细胞 (CTC) 与生存率低相关。尽管许多上皮细胞粘附分子和细胞角蛋白 (EpCAM+CK+) 呈阳性的物体不计为 CTC,但它们可能是生存的重要预测因子。我们评估了这些对象与前列腺癌患者生存率之间的关联。患者和方法:本次随访研究包括 179 名去势抵抗性前列腺癌患者。 CellSearch 用于分离 EpCAM+ 对象并染色 DNA、细胞角蛋白和 CD45。根据 63 个独立样本中预定义的形态外观,所有 EpCAM+CK+ 对象被细分为七类。使用Kaplan-Meier 和Cox 回归分析研究每个类别与生存的关联。结果:每个EpCAM+CK+CD45- 类别与总生存有很强的相关性(P < 0.001)。其中包括小肿瘤微粒(S-TMP),它不需要细胞核,因此无法转移。任何类别中的物体数量越多,生存率就越低。一个好的预测模型包括大肿瘤细胞碎片(L-TCF)、年龄、血红蛋白和乳酸脱氢酶。使用S-TMP或CTC代替L-TCF的模型表现相似。结论:不符合CTC严格定义的EpCAM+CK+CD45-是生存的强预后标志物。
Background: Presence of five or more circulating tumor cells (CTC) in patients with metastatic carcinomas is associated with poor survival. Although many objects positive for epithelial cell adhesion molecules and cytokeratin (EpCAM+CK+) are not counted as CTC, they may be an important predictor for survival. We evaluated the association between these objects and survival in patients with prostate cancer.Patients and methods: Included in this follow-up study were 179 patients with castration-resistant prostate cancer. CellSearch was used to isolate EpCAM+ objects and to stain DNA, cytokeratin and CD45. All EpCAM+CK+ objects were subdivided into seven classes on the basis of predefined morphological appearance in 63 independent samples. Association of each class with survival was studied using Kaplan-Meier and Cox regression analyses.Results: Each EpCAM+CK+CD45- class showed a strong association with overall survival (P < 0.001). This included small tumor microparticles (S-TMP), which did not require a nucleus and thus are unable to metastasize. A higher number of objects in any class was associated with decreased survival. A good prediction model included large tumor cell fragments (L-TCF), age, hemoglobin and lactate dehydrogenase. Models with S-TMP or CTC instead of L-TCF performed similarly.Conclusion: EpCAM+CK+CD45- that do not meet strict definitions for CTC are strong prognostic markers for survival.