Stem cell marker aldehyde dehydrogenase 1-positive breast cancers are characterized by negative estrogen receptor, positive human epidermal growth factor receptor type 2, and high Ki67 expression

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+.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aldehyde Dehydrogenase / metabolism*
  • Aldehyde Dehydrogenase 1 Family
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / surgery
  • Combined Modality Therapy
  • Estrogen Receptor alpha
  • Female
  • Humans
  • Immunohistochemistry
  • Isoenzymes / metabolism*
  • Ki-67 Antigen / metabolism
  • Lymphatic Metastasis
  • Mastectomy
  • Middle Aged
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology*
  • Receptor, ErbB-2 / metabolism*
  • Receptors, Estrogen / deficiency
  • Receptors, Estrogen / metabolism
  • Retinal Dehydrogenase


  • ESR1 protein, human
  • Estrogen Receptor alpha
  • Isoenzymes
  • Ki-67 Antigen
  • Receptors, Estrogen
  • Aldehyde Dehydrogenase 1 Family
  • Aldehyde Dehydrogenase
  • ALDH1A1 protein, human
  • Retinal Dehydrogenase
  • ERBB2 protein, human
  • Receptor, ErbB-2