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

Abstract

Recently, aldehyde dehydrogenase (ALDH) 1 has been identified as a reliable marker for breast cancer stem cells. E vidence has recently been accumulating to support the cancer stem cell hypothesis for solid tumors, including breast cancer, which holds that cancers are driven by a small subpopulation of stem cells that are capable of self-renewal and give rise to multipotent progenitor cells that ultimately differentiate into all cell types within the tumor.(1) Al-Hajj et al. were the first to distinguish tumorigenic from non-tumorigenic cancer cells by using the cell surface markers CD44 and CD24.(2) They have shown that cancer stem cells in a population of tumor cells are enriched with the CD44 + and CD24 -phenotype because as few as 100 tumor cells with this phenotype were able to produce tumors in immunodeficient mice, whereas tumor cells with other CD44 and CD24 phenotypes were unable or rarely able to produce tumors even when as many as 10 5 -10 6 tumor cells were inoculated into such mice. + cancer stem cells may well be clinically useful for patient prognosis. In the study reported here, we therefore investigated the clinicopathological characteristics of breast cancers with ALDH1 + cancer stem cells and also compared ALDH1 expression in primary tumors and axillary metastases. In addition, the ER, Ki67, and HER2 status of ALDH1 + tumor cells was investigated on a cell-by-cell basis by means of double immunohistochemical staining for further characterization of the phenotype of breast cancer stem cells. Materials and MethodsPatients and breast tumor tissues. Tumor tissue samples were obtained from 203 primary breast cancer patients (mean age, 52.6 years; range, 32-86 years) who underwent mastectomy or breast-conserving surgery between January 1993 and December 1997 at Osaka University Hospital, Osaka, Japan. Tumor tissues were fixed in 10% buffered formalin and embedded in paraffin. This study protocol was approved by the Ethics Committee of Osaka University.For adjuvant therapy, 85 patients were treated with hormonal therapy (tamoxifen, n = 74; toremifene, n = 7; gosereline, n = 3; or gosereline + tamoxifen, n = 1), 22 with chemotherapy (fluoropyrimidine, n = 8; cyclophosphamide + methotrexate + 5-fluorouracil, n = 7; cyclophosphamide + adriamycin + 5-fluorouracil, n = 4; or high-dose chemotherapy, n = 3), and 84 with chemohormonal therapy (fluoropyrimidine, n = 37; cyclophosphamide + methotrexate + 5-fluorouracil, n = 25; cyclophosphamide + adriamycin + 5-fluorouracil, n = 20; or high-dose chemotherapy, n = 2; plus tamoxifen, n = 78; toremifene, n = 1; gosereline, n = 3; or gosereline + tamoxifen, n = 2). Twelve patients received no adjuvant therapy.

High Expression of Stem Cell Marker ALDH1 is Associated with Reduced BRCA1 in Invasive Breast Carcinomas

“…In a series of 127 breast carcinomas we were unable to verify correlations between ALDH1 cytoplasmic expression and histological grade, although previous studies stated that ALDH1 positive cells (CSC) were significantly associated with high grade tumours and poor overall survival indicating that ALDH1 status maybe an indicator of aggressive breast carcinomas (Ginestier and Wicha, 2007;Morimoto et al, 2009;Nalwoga et al, 2010;Yoshioka et al, 2011). This is probably due to the fact that the study was restricted to limited sample size and therefore warrants further investigation with a larger number of samples.…”

“…Therefore, determination of ALDH1 cancer stem cells may be clinically useful for patient's prognosis. CSC positive breast cancers, particularly ALDH1 positive cancers have been showed that to be more likely negative for ER and PR, but positive for HER2 and Ki67 correlating with more aggressive breast cancer subtypes (Morimoto et al, 2009;Zhou et al, 2010). Expression of ALDH1 was seen in stromal cells as well as epithelial cells of breast tumours which is associated with good outcome, concluding that tumour environment play a crucial role in determining the prognostic impact of stem cells Resetkova et al, 2010).…”

Prediction of pathologic complete response to sequential paclitaxel and 5-fluorouracil/epirubicin/cyclophosphamide therapy using a 70-gene classifier for breast cancers

“…13 ER status and PR status were defined as positive when !10% tumor cells had immunohistochemically positive staining (ER: clone 6F11; Ventana, Tokyo, Japan; PR: clone16; SRL Inc., Tokyo, Japan). Ki-67 status was defined as positive when !20% tumor cells were stained positive.…”

Cancer stem cells are new vistas for predicting the course of breast cancer

“…Высокая экспрессия ALDH1 коррелирует с более агрессивными подтипами РМЖ [8]. В работах разных авторов было показано, что более высокая экспрессия ALDH1 связана с резистентностью к химиотерапии и низкой выживаемостью [9,10].…”