Tumorbiologisches Labor der Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, Campus Innenstadt, Klinikum der Ludwig-Maximilians-Universität, Munich, Germany.
Transl Oncol. 2012 Dec;5(6):475-85. doi: 10.1593/tlo.12310. Epub 2012 Dec 1.
Hormone therapy and anti-ErbB2 therapies are prescribed according to the hormone receptor [estrogen receptor α (ERα)/progesterone receptor] and ErbB2 status of the initial tumor, but it appears that circulating tumor cells (CTCs) and, consequently, the metastatic cells may have a different receptor status. As an attempt to meet the crucial need for identification of the subpopulation of patients that will benefit from more individualized therapies, rapidly evolving therapies should allow a profiling of the tumors and/or of the CTCs. We established a triple fluorescence staining using eight cell lines to visualize the CTCs (cytokeratin detection) and then to define their individual ERα and ErbB2 status. Afterward, we used this method for blood samples from 26 metastatic breast cancer patients. We identified major differences of ERα levels between the cell lines and even within one cell line. For the metastatic patients, we detected and characterized CTCs in 38.5% of the patients with a total of 92 CTCs. We could demonstrate that at least 69.6% of the CTCs exhibit an ERα and/or ErbB2 status different from the status of the primary tumor and that the CTCs from only 30% of the patients had no change of receptor status. Strikingly, heterogeneities of the status, aggregation, and size clearly appear within the CTCs. The data we generated outline the importance of a profiling not only of tumors but also of CTCs to establish individualized treatments. CTCs may then appear as new prognosis and treatment marker for both metastatic and adjuvant breast cancers.
激素治疗和抗-ErbB2 治疗是根据初始肿瘤的激素受体（雌激素受体 α [ERα]/孕激素受体）和 ErbB2 状态来开处方的，但似乎循环肿瘤细胞（CTC），进而转移细胞，可能具有不同的受体状态。为了满足鉴定将从更个体化治疗中获益的患者亚群的关键需求，快速发展的治疗方法应该允许对肿瘤和/或 CTC 进行分析。我们使用八种细胞系建立了三重荧光染色，以可视化 CTC（细胞角蛋白检测），然后定义其个体 ERα 和 ErbB2 状态。之后，我们将该方法用于 26 名转移性乳腺癌患者的血液样本。我们发现细胞系之间甚至在一个细胞系内 ERα 水平存在很大差异。对于转移性患者，我们在 38.5%的患者中检测到并表征了 CTC，总共检测到 92 个 CTC。我们可以证明至少 69.6%的 CTC 表现出与原发性肿瘤不同的 ERα 和/或 ErbB2 状态，并且只有 30%的患者的 CTC 没有受体状态的变化。引人注目的是，CTC 内的状态、聚集和大小的异质性明显出现。我们生成的数据突出了不仅对肿瘤而且对 CTC 进行分析以建立个体化治疗的重要性。CTC 可能成为转移性和辅助性乳腺癌的新预后和治疗标志物。
