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三阴性乳腺癌（TNBC）是乳腺癌的一个亚型，具有高度浸润性，预后差。同时，癌症干细胞（CSC）也具有很强的致瘤潜力，可能部分参与TNBC的浸润行为。既往研究表明TNBC细胞系和组织富含CSC，动物模型进一步实验表明从TNBC细胞系分离出的CSC具有较高致瘤性。 2017年4月，美国巴尔的摩《医学》在线发表中国医学科学院北京协和医学院肿瘤医院、国家癌症中心、山东省肿瘤医院、山东省肿瘤防治研究院、首都医科大学附属北京地坛医院的研究报告，通过分析TNBC组织乳腺CSC标记物醛脱氢酶1（ALDH1）的表达，确定了CSC与TNBC之间的临床相关性。 该研究通过免疫组织化学染色，使用ALDH1A1初次应答抗体，评定了158例TNBC患者石蜡包埋肿瘤组织的ALDH1水平。由两位病理医生独立进行染色评定，根据阳性细胞的百分比和密度评定ALDH1表达水平，并分析了ALDH1表达免疫组织化学染色与临床指标的相关性。 结果发现，其中88例（55.7%）有ALDH1表达。 临床病理指标分析显示，ALDH1免疫组织化学染色与肿瘤大小和分期有显著相关性（P=0.02，P=0.04）。 生存分析显示，ALDH1表达患者的的无复发生存（RFS）和总生存（OS）时间较短（P=0.01，P=0.001）。 此外，比例风险模型（Cox）多变量分析显示ALDH1表达是RFS和OS的独立预后指标（P=0.04；P=0.04）。 因此，肿瘤细胞ALDH1免疫组织化学染色是TNBC患者RFS和OS的独立预后指标。 Medicine (Baltimore). 2017 Apr;96(14):e6561. Aldehyde dehydrogenase 1 (ALDH1) expression is an independent prognostic factor in triple negative breast cancer (TNBC). Ma F, Li H, Li Y, Ding X, Wang H, Fan Y, Lin C, Qian H, Xu B. National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Shandong Cancer Hospital/Institute, Jinan, Shandong; Beijing Ditan Hospital, Capital Medical University. Triple negative breast cancer (TNBC) is a subset of breast cancer that is highly aggressive and has a poor prognosis. Meanwhile, cancer stem cells (CSCs) are also characterized by a strong tumorigenic potential, which might be partly responsible for the aggressive behavior of TNBC. We previously showed that CSCs are enriched in TNBC cell lines and tissues. Further experiments in animal models revealed higher tumorigenicity of CSCs sorted from TNBC cell lines. In this study, we aimed to determine the clinical relationship between CSCs and TNBC by exploring the expression of aldehyde dehydrogenase 1 (ALDH1), which is a putative marker of breast CSCs, in TNBC tissues. ALDH1 levels in paraffin-embedded tumor tissues from 158 TNBC patients were evaluated by immunohistochemistry staining using an ALDH1A1 primary antibody. Staining evaluation was performed independently by two pathologists, and the expression level of ALDH1 was evaluated in terms of the percentage and intensity of positive cells. The association of immunohistochemistry staining of ALDH1 expression with clinical parameters was also analyzed. ALDH1 expression in tumor cells was observed in 88 out of 158 cases (55.7%). Analysis of clinicopathological parameters showed that the immunohistochemistry staining of ALDH1 was significantly correlated with tumor size (P=0.02) and stage (P=0.04). Survival analysis in patients with ALDH1 expression demonstrated shorter relapse-free survival (RFS) and overall survival (OS) times (P=0.01; P=0.001). Moreover, Cox multivariate analysis revealed that ALDH1 expression was an independent prognostic indicator of RFS and OS (P=0.04; P=0.04). Immunohistochemistry staining of ALDH1 in tumor cells is an independent prognostic indicator of RFS and OS in TNBC patients. PMID: 28383433 DOI: 10.1097/MD.0000000000006561
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