Morimoto Koji, Kim Seung Jin, Tanei Tomonori, Shimazu Kenzo, Tanji Yoshio, Taguchi Tetsuya, Tamaki Yasuhiro, Terada Nobuyuki, Noguchi Shinzaburo
Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Suita City, Osaka, Japan.
Cancer Sci. 2009 Jun;100(6):1062-8. doi: 10.1111/j.1349-7006.2009.01151.x. Epub 2009 Mar 9.
Recently, aldehyde dehydrogenase (ALDH) 1 has been identified as a reliable marker for breast cancer stem cells. The aim of our study was to investigate the clinicopathological characteristics of breast cancers with ALDH1+ cancer stem cells. In addition, the distribution of ALDH1+ tumor cells was compared on a cell-by-cell basis with that of estrogen receptor (ER)+, Ki67+, or human epidermal growth factor receptor type 2 (HER2)+ tumor cells by means of double immunohistochemical staining. Immunohistochemical staining of ALDH1 was applied to 203 primary breast cancers, and the results were compared with various clinicopathological characteristics of breast cancers including tumor size, histological grade, lymph node metastases, lymphovascular invasion, ER, progesterone receptor, HER2, Ki67, and topoisomerase 2A as well as prognosis. Immunohistochemical double staining of ALDH1 and ER, Ki67, or HER2 was also carried out to investigate their distribution. Of the 203 breast cancers, 21 (10%) were found to be ALDH1+, and these cancers were significantly more likely to be ER- (P = 0.004), progesterone receptor- (P = 0.025), HER2+ (P = 0.001), Ki67+ (P < 0.001), and topoisomerase 2A+ tumors (P = 0.012). Immunohistochemical double staining studies showed that ALDH1+ tumor cells were more likely to be ER-, Ki67-, and HER2+ tumor cells. Patients with ALDH1 (score 3+) tumors showed a tendency (P = 0.056) toward a worse prognosis than did those with ALDH1- tumors. Breast cancers with ALDH1+ cancer stem cells posses biologically aggressive phenotypes that tend to have a poor prognosis, and ALDH1+ cancer stem cells are characterized by ER-, Ki67-, and HER2+.
最近,醛脱氢酶(ALDH)1已被确定为乳腺癌干细胞的可靠标志物。我们研究的目的是调查具有ALDH1+癌干细胞的乳腺癌的临床病理特征。此外,通过双重免疫组织化学染色,逐细胞比较ALDH1+肿瘤细胞与雌激素受体(ER)+、Ki67+或人表皮生长因子受体2型(HER2)+肿瘤细胞的分布情况。对203例原发性乳腺癌进行ALDH1免疫组织化学染色,并将结果与乳腺癌的各种临床病理特征进行比较,包括肿瘤大小、组织学分级、淋巴结转移、淋巴管浸润、ER、孕激素受体、HER2、Ki67、拓扑异构酶2A以及预后情况。还进行了ALDH1与ER、Ki67或HER2的免疫组织化学双重染色,以研究它们的分布。在203例乳腺癌中,发现21例(10%)为ALDH1+,这些癌症更有可能是ER-(P = 0.004)、孕激素受体-(P = 0.025)、HER2+(P = 0.001)、Ki67+(P < 0.001)和拓扑异构酶2A+肿瘤(P = 0.012)。免疫组织化学双重染色研究表明,ALDH1+肿瘤细胞更有可能是ER-、Ki67-和HER2+肿瘤细胞。与ALDH1-肿瘤患者相比,ALDH1(评分3+)肿瘤患者预后有较差的趋势(P = 0.056)。具有ALDH1+癌干细胞的乳腺癌具有生物学侵袭性表型,预后往往较差,且ALDH1+癌干细胞的特征为ER-、Ki67-和HER2+。