Association of Breast Cancer Stem Cells Identified by Aldehyde Dehydrogenase 1 Expression with Resistance to Sequential Paclitaxel and Epirubicin-Based Chemotherapy for Breast Cancers
Association of Breast Cancer Stem Cells Identified by Aldehyde Dehydrogenase 1 Expression with Resistance to Sequential Paclitaxel and Epirubicin-Based Chemotherapy for Breast Cancers
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DOI：
10.1158/1078-0432.ccr-08-1479
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发表时间：
2009-06-15
影响因子：
11.5
通讯作者：
Noguchi, Shinzaburo
中科院分区：
文献类型：
--
作者：
Tanei, Tomonori;Morimoto, Koji;Noguchi, Shinzaburo
目的：乳腺癌干细胞已被证明与体外化疗耐药相关，但其临床意义仍有待阐明。本研究的目的是探讨癌症干细胞对人类乳腺癌化疗耐药是否具有临床意义。 实验设计：本研究纳入了接受新辅助化疗（包括序贯紫杉醇和表柔比星化疗）的原发性乳腺癌患者 (n = 108)。通过对新辅助化疗前后获得的肿瘤组织中的 CD44/CD24 和乙醛脱氢酶 1 (ALDH1) 进行免疫组织化学染色来鉴定乳腺癌干细胞。 CD44(+)/CD24(-)肿瘤细胞或ALDH1阳性肿瘤细胞被认为是干细胞。结果：30例(27.8%)患者达到病理完全缓解(pCR)。 ALDH1 阳性肿瘤与低 pCR 率显着相关（9.5% vs 32.2%；P = 0.037），但 CD44(+)/CD24(-) 肿瘤细胞比例与 pCR 率之间没有显着相关性。在78名未达到pCR的患者中研究了新辅助化疗前后CD44(+)/CD24(-)或ALDH1阳性肿瘤细胞比例的变化。新辅助化疗后，ALDH1阳性肿瘤细胞的比例显着增加（P < 0.001），但CD44（+）/CD24（-）肿瘤细胞的比例没有增加。结论：我们的研究结果表明，ALDH1阳性的乳腺癌干细胞在化疗耐药中发挥着重要作用，而CD44（+）/CD24（-）则不然。因此，ALDH1 阳性似乎是比 CD44(+)/CD24(-) 更显着的预测乳腺癌干细胞化疗耐药性的标志物。
Purpose: Breast cancer stem cells have been shown to be associated with resistance to chemotherapy in vitro, but their clinical significance remains to be clarified. The aim of this study was to investigate whether cancer stem cells were clinically significant for resistance to chemotherapy in human breast cancers.Experimental Design: Primary breast cancer patients (n = 108) treated with neoadjuvant chemotherapy consisting of sequential paclitaxel and epirubicin-based chemotherapy were included in the study. Breast cancer stem cells were identified by immunohistochemical staining of CD44/CD24 and aldehyde dehydrogenase 1 (ALDH1) in tumor tissues obtained before and after neoadjuvant chemotherapy. CD44(+)/CD24(-) tumor cells or ALDH1-positive tumor cells were considered stem cells.Results: Thirty (27.8%) patients achieved pathologic complete response (pCR). ALDH1-positive tumors were significantly associated with a low pCR rate (9.5% versus 32.2%; P = 0.037), but there was no significant association between CD44(+)/CD24(-) tumor cell proportions and pCR rates. Changes in the proportion of CD44(+)/CD24(-) or ALDH1-positive tumor cells before and after neoadjuvant chemotherapy were studied in 78 patients who did not achieve pCR. The proportion of ALDH1-positive tumor cells increased significantly (P < 0.001) after neoadjuvant chemotherapy, but that of CD44(+)/CD24(-) tumor cells did not.Conclusions: Our findings suggest that breast cancer stem cells identified as ALDH1-positive, but not CD44(+)/CD24(-), play a significant role in resistance to chemotherapy. ALDH1-positive thus seems to be a more significantly predictive marker than CD44(+)/CD24(-) for the identification of breast cancer stem cells in terms of resistance to chemotherapy.