ALDH+/CD44+ cells in breast cancer are associated with worse prognosis and poor clinical outcome
ALDH+/CD44+ cells in breast cancer are associated with worse prognosis and poor clinical outcome
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DOI：
10.1016/j.yexmp.2015.11.032
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发表时间：
2016-02-01
影响因子：
3.6
通讯作者：
Ye, Feng
中科院分区：
文献类型：
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作者：
Qiu, Yan;Pu, Tianjie;Ye, Feng
背景：乳腺癌干细胞（BCSCs）在肿瘤转移中发挥着重要作用，并导致了显著的负面临床结果。近年来，醛脱氢酶（ALDH）和CD44阳性(ALDH（+)/CD44(+)）在体外/体内研究中被确定为BCSCs的标志物。本研究的目的是评估ALDH(+)/CD44（+）细胞在乳腺癌中的患病率，以及这两个标志物与临床病理特征和临床结果的关系。材料和方法：我们研究了144例福尔马林固定石蜡包埋（FFPE）乳腺癌组织中ALDH1A3(+)/CD44（+）细胞的患病率。采用单免疫组化和双免疫组化（dIHC）对组织进行ALDH1A3和CD44染色。分析ALDH1A3(+)/CD44细胞阳性率与患者临床病理特征及临床转归的关系。结果：39例（27.1%）患者存在ALDH1A3(+)/CD44（+）细胞。通过Mann-Whitney U检验、Pearson Chi-square检验或Fisher精确检验表明，ALDH1A3(+)/CD44（+）细胞的流行与初始手术后肿瘤大小（p = 0.001）、淋巴结转移情况（p = 0.043）、临床分期（p = 0.021）和远处转移（p = 0.001）密切相关。在单变量生存分析中，ALDH1A3(+)/CD44（+）肿瘤细胞的存在与无病生存（DFS）和总生存（OS）均呈显著负相关(p(DFS) < 0.001；p(OS) < 0.001)。采用Cox比例风险模型的多因素分析进一步证实了ALDH1A3(+)/CD44（+）肿瘤的阴性临床结局(p(DFS) < 0.001, HR = 3.155；p(OS) = 0.001, HR = 3.193)。对于化疗（p -DFS < 0.001; p(OS) = 0.001）、放疗(p(DFS) = 0.004；p(OS) = 0.004)，内分泌治疗(p(DFS) < 0.001；p(OS) < 0.001)。结论：综上所述，我们的研究结果表明，乳腺癌中ALDH1A3(+)/CD44（+）肿瘤细胞的患病率与不良预后因素显著相关，有利于不良预后。(C) 2015爱思唯尔公司版权所有。
Background: Breast cancer stem cells (BCSCs) play essential roles in tumor metastasis and contribute to remarkably negative clinical outcomes. Recently, aldehyde dehydrogenase (ALDH) and CD44 positivity (ALDH(+)/CD44(+)) was identified as a marker of BCSCs in vitro/in vivo studies. The aim of this study was to evaluate the prevalence of ALDH(+)/CD44(+) cells in breast cancer and the association of these two markers with clinicopathological features and clinical outcomes.Materials and methods: We investigated the prevalence of ALDH1A3(+)/CD44(+) cells in a cohort of 144 formalin-fixed, paraffin-embedded (FFPE) breast cancer tissues. The tissues were stained for ALDH1A3 and CD44 by single and dual immunohistochemistry (dIHC). The associations among the prevalence of ALDH1A3(+)/CD44 cells, the clinicopathological features and the clinical outcomes of the patients were also analyzed.Results: ALDH1A3(+)/CD44(+) cells were present in 39 patients (27.1%). By the Mann-Whitney U test, the Pearson Chi-square test or Fisher's exact test, it was demonstrated that the prevalence of ALDH1A3(+)/CD44(+) cells was closely correlated with larger tumor size (p = 0.001), nodal metastasis status (p = 0.043), more advanced clinical stage (p = 0.021) and distant metastasis after initial surgery (p = 0.001). In a univariate survival analysis, the presence of ALDH1A3(+)/CD44(+) tumor cells had a significant negative association with both disease-free survival (DFS) and overall survival (OS) (p(DFS) < 0.001; p(OS) < 0.001). The negative clinical outcomes in ALDH1A3(+)/CD44(+) tumors were further confirmed by a multivariate analysis using Cox proportional hazard models (p(DFS) < 0.001, HR = 3.155; p(OS) = 0.001, HR = 3.193). This was also true with respect to the clinical treatment regimens of chemotherapy (P-DFS < 0.001; p(OS) = 0.001), radiotherapy (p(DFS) = 0.004; p(OS) = 0.004), and endocrine therapy (p(DFS) < 0.001; p(OS) < 0.001).Conclusion: In summary, our results indicate that the prevalence of ALDH1A3(+)/CD44(+) tumor cells in breast cancer is significantly associated with worse prognostic factors and favors a poor prognosis. (C) 2015 Elsevier Inc. All rights reserved.