早期乳腺癌患者骨髓中癌症干细胞的临床相关性。
Clinical relevance of cancer stem cells in bone marrow of early breast cancer patients.
机构信息
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, USA; Department of Endocrinology and Molecular and Clinical Oncology, University of Naples Federico II, Naples, Italy.
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, USA.
出版信息
Ann Oncol. 2013 Oct;24(10):2515-2521. doi: 10.1093/annonc/mdt223. Epub 2013 Jun 24.
BACKGROUND
Cancer stem cells (CSCs) are epithelial tumor cells that express CD44(+)CD24(-/lo). CSCs can be further divided into those that have aldehyde dehydrogenase (ALDH) activity (Aldefluor(+)) and those that do not. We hypothesized that if CSCs are responsible for tumor dissemination, their presence in bone marrow (BM) would be prognostic in early stages of breast cancer (EBC) patients.
PATIENTS AND METHODS
BM aspirates were collected at the time of surgery from 108 patients with EBC. BM was analyzed for CSCs and ALDH activity by flow cytometry. Overall survival and disease-free survival (DFS) were calculated from the date of diagnosis and analyzed with Kaplan-Meier survival plots. Cox multivariate proportional hazards model was also carried out.
RESULTS
Patients with CSCs in BM had a hazard ratio (HR) of 8.8 for DFS (P = 0.002); patients with Aldefluor(+) CSCs had a HR of 5.9 (P = 0.052) for DFS. All deceased patients (n = 7) had CSCs in BM. In multivariate analysis, the presence of CSCs in BM was a prognostic factor of DFS (HR = 15.8, P = 0.017).
CONCLUSIONS
The presence of BM metastasis is correlated with CSCs and these CSCs irrespective of ALDH activity are an independent adverse prognostic factor in EBC patients.
背景
癌症干细胞（CSCs）是表达 CD44(+)CD24(-/lo) 的上皮肿瘤细胞。CSCs 可以进一步分为具有醛脱氢酶（ALDH）活性（Aldeefluor(+)）的和不具有 ALDH 活性的。我们假设，如果 CSCs 负责肿瘤扩散，那么它们在骨髓（BM）中的存在将在乳腺癌（EBC）早期患者中具有预后意义。
患者和方法
从 108 例 EBC 患者的手术时采集 BM 抽吸物。通过流式细胞术分析 BM 中的 CSCs 和 ALDH 活性。从诊断之日起计算总生存期和无病生存期（DFS），并通过 Kaplan-Meier 生存图进行分析。还进行了 Cox 多变量比例风险模型分析。
结果
BM 中有 CSCs 的患者 DFS 的危险比（HR）为 8.8（P = 0.002）；BM 中 Aldefluor(+)CSCs 的患者 DFS 的 HR 为 5.9（P = 0.052）。所有死亡患者（n = 7）的 BM 中均有 CSCs。在多变量分析中，BM 中 CSCs 的存在是 DFS 的预后因素（HR = 15.8，P = 0.017）。
结论
BM 转移的存在与 CSCs 相关，这些 CSCs 不论 ALDH 活性如何，都是 EBC 患者独立的不良预后因素。
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