CD44^+/CD24^(-/low)/ABCG2^-乳腺癌干细胞比例增高与临床治疗相关的探索性研究  

Pilot study on the correlation between high incidence of CD44^+/CD24^(-/low)/ABCG2^- cells and poor prognosis in breast cancer

作　　者：龚继芳[1] 袁艳华[1] 宋国红[1] 余靖[1] 贾军[1] 任军[1] 

机构地区：[1]北京大学临床肿瘤学院北京肿瘤医院暨北京市肿瘤防治研究所内科,北京100142

出　　处：《北京大学学报（医学版）》2008年第5期465-470,共6页Journal of Peking University:Health Sciences

摘　　要：目的:研究CD44+/CD24-/low/ABCG2-细胞与临床治疗及预后的相关性。方法:收集北京大学临床肿瘤学院经病理诊断为乳腺浸润性导管癌患者的手术切除石蜡标本共43例,进行免疫组织化学检测ABCG2和CD44/CD24双染的表达情况,分析其与预后的相关性。同时收集北京大学临床肿瘤学院晚期乳腺浸润性导管癌患者共10例,分别于治疗前及化疗2周期后抽取空腹静脉血4mL,流式细胞仪检测CD45-/CD44+/CD24-/low/ABCG2-的细胞比例,分析其与治疗的相关性,并与健康志愿者进行对照。结果:43例患者中,术后5年内复发23例,5年内无复发20例。免疫组织化学检测表明,复发组ABCG2表达高于术后无复发组,但差异无统计学意义(78.3%vs60.0%,P=0.32),且与生存无相关性(P=0.086)。CD44+/CD24-双染细胞>10%者在复发组更常见,两组之间差异有统计学意义(65.2%vs35.0%,P=0.048),这部分患者的无病生存期更短,但不是独立预后因素。流式细胞检测CD45-/CD44+/CD24-/low/ABCG2-的细胞在晚期乳腺癌患者的数量为1～3725个/105(中位数为679个/105),健康志愿者中该细胞数为0～98个/105(中位数为12个/105)。该细胞数目在化疗前后出现了变化,但与治疗效果的相符性没有得出统计学意义。结论:乳腺癌组织中,CD44+/CD24-/low乳腺癌干细胞的比例与患者的预后相关,而乳腺癌患者外周血中的CD44+/CD24-/low/ABCG2-的细胞数目高于健康志愿者,其与临床疗效的相关性仍需进一步研究。Objective：To explore whether the CD44^＋/CD24^-/low/ABCG2^-（ATP binding cassette superfamily G member 2 ） cells are associated with prognosis and clinical response in breast cancer patients. Methods：We investigated the paraffin-embedded tissues of 43 breast cancer patients with （23 cases） and without （ 20 cases ） recurrences. Double-staining immunohistochemistry （IHC） was applied for the detection of CD44 ^＋/CD24^-/low cells and single-staining IHC for ABCG2. Flow cytometry was used to analyze the CD45^-/CD44^＋CD24^-/low/ABCG2^- cells in 4 mL peripheral blood of patients with metastasis breast cancer and 11 healthy female volunteers as controls. Results： The positive rate of ABCG2 in recurrence-group was higher but with no difference compared with controls （ 78.3 % vs 60. 0% , P = 0.32）. Doublestaining IHC revealed that the percentage of CD44^＋/CD24^-/low cells was higher in recurrence group than non-recurrence group （65.2% vs 35.0%,P=0.048） and higher percentage of CD44^＋/ CD24^-/low cells was significant associated with poor overall survival（P=0. 031）. Patients with higher percentage of CD44^＋/CD24^-/low cells have shorter disease free survival （DFS）, but have no statistical significance. Flow cytometry revealed that the CD45^-/CD44^＋/CD24^-/low/ABCG2^- cells were higher in breast cancer patients than those of the volunteers （ median 679/105 cells vs 12/105 cells）. The cell number of this subset was affected by chemotherapy but was not statistically consistent with clinical response. Conclusion：Our study suggests that CD44^＋/CD24^-/low breast cancer stem cells in tumor tissue may be associated with poor prognosis. The incidence of CD44^＋/CD24^-/low/ABCG2^- cells in peripheral blood is more frequent in breast cancer patients but further investigation should be made to explore the relationship of this subset and disease prognosis.

关 键 词：乳腺肿瘤 肿瘤干细胞 抗药性 肿瘤 

分 类 号：R737.9[医药卫生—肿瘤]