Aldehyde dehydrogenase 1 expression predicts poor prognosis in triple-negative breast cancer

Ohi, Yasuyo; Umekita, Yoshihisa; Yoshioka, Takako; Souda, Masakazu; Rai, Yoshiaki; Sagara, Yoshiaki; Sagara, Yasuaki; Sagara, Yoshiatsu; Tanimoto, Akihide

doi:10.1111/j.1365-2559.2011.03884.x

Cited by 74 publications

(60 citation statements)

References 6 publications

(14 reference statements)

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“…In contrast, we found that ALDH1 expression was associated with Her2/neu overexpression. With similar results currently emerging from groups in Japan, we propose that ALDH1 expression is associated with Her2/neu-overexpressing breast cancers in Asian patients [11,14].…”

Section: Discussionsupporting

confidence: 59%

“…Some studies have reported the association of ALDH1 expression with poor prognosis and factors associated with aggressive disease such as estrogen receptor (ER) negativity and the expression of basal-like markers [11,12]. ALDH1 positivity has also been shown to be correlated with poor prognosis, especially in lymph node-positive cancers, triple-negative cancers, and inflammatory breast cancers [13][14][15]. Furthermore, ALDH1 expression has been shown to be associated with resistance to chemotherapy [16,17].…”

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confidence: 99%

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Association of aldehyde dehydrogenase 1 expression and biologically aggressive features in breast cancer

Kang¹,

Jung

Woo³

et al. 2014

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Aldehyde dehydrogenase 1 (ALDH1) has been regarded as a breast cancer stem cell marker. Several studies have reported that ALDH1 expression is associated with poor prognosis in breast cancer. We aimed, therefore, to determine the prognostic value of ALDH1 expression and its association with several biomarkers in breast cancer tissue using immunohistochemistry. Furthermore, we investigated the characteristics of and differences between cellular and stromal expression of ALDH1. We performed tissue microarray (TMA) analysis of 425 breast cancer tissue samples collected during surgery. Immunohistochemical staining was then performed to measure the expression of ALDH1 and other breast cancer biomarkers. Statistical analysis of the relationship between ALDH1 expression and clinicopathologic characteristics was performed for 390 TMA samples. We found that ALDH1 was expressed in 71 cases (18.2%) in the tumor cells and/or stroma. Of these cases, 38 (9.7%) showed ALDH1 expression in tumor cells and 38 (9.7%) showed ALDH1 expression in the stroma. ALDH1 expression was significantly associated with markers of a poor prognosis, such as young age, estrogen receptor negativity, progesterone receptor negativity, a high histological grade, and a high Ki-67 index. However, ALDH1 expression was not associated with p53, transforming growth factor-beta, Gli-1, YKL-40, or sonic hedgehog expression status. With regard to the expression site, the clinical characteristics did not differ between cases of cellular expression and those of stromal expression. However, ALDH1 expression in tumor cells was correlated with hormone receptor status, histological grade, molecular subtype, epidermal growth factor receptor expression status, and cytokeratin 5/6 expression status while stromal expression of ALDH1 was only correlated with hormone receptor status. Overall, these findings suggest that ALDH1 expression in tumor tissue is associated with a biologically aggressive phenotype.

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Section: Discussionsupporting

confidence: 59%

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confidence: 99%

Association of aldehyde dehydrogenase 1 expression and biologically aggressive features in breast cancer

Kang¹,

Jung

Woo³

et al. 2014

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“…Several investigators have demonstrated its clinical significance as a prognostic indicator of breast cancer, and may become a promising target for cancer therapy. ALDH1 expression in carcinoma cells is an independent prognostic factor in TNBC patients (Ohi et al, 2011). In addition, Li et al study support the concept that the expression of ALDH1 is higher in TNBC than in non-TNBC, which may be clinically meaningful for a better understanding of the poor prognosis of TNBC patients .…”

Section: Biomarkers For Targeted Therapysupporting

confidence: 60%

Recent Progress in Triple Negative Breast Cancer Research

Mouh¹,

Mzibri²,

Slaoui³

et al. 2016

Asian Pacific Journal of Cancer Prevention

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Triple-negative breast cancer (TNBC) is defined as a type of breast carcinoma that is negative for expression of oestrogene and progesterone hormone receptors (ER, PR) and HER2. This form of breast cancer is marked by its aggressiveness, low survival rate and lack of specific therapies. Recently, important molecular characteristics of TNBC have been highlighted and led to the identification of some biomarkers that could be used in diagnosis, as therapeutic targets or to assess the prognosis. In this review, we summarize recent progress in TNBC research focusing on the genetic and epigenetic alterations of TNBC and the potential use of these biomarkers in the targeted therapy for better management of TNBC.

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“…In this study, we investigated two cancer stem-like cell/tumor-initiating cell markers. Aldehyde dehydrogenase 1(ALDH1) is a cytosolic isoform of ALDH, and high levels of its activity are seen not only in hematopoietic stem/ progenitor cells but also in solid cancers (eg, breast, 16,17 colorectal, 18 pancreas, 19 bladder 20 and prostate 21 cancers). Furthermore, expression of ALDH1 is a predictor of poor clinical outcome in the breast, 16,22 lung, 23 pancreatic 19 and bladder 20 cancers.…”

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confidence: 99%

Prognostic impact of the expression of ALDH1 and SOX2 in urothelial cancer of the upper urinary tract

et al. 2013

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Aldehyde dehydrogenase 1 (ALDH1) and sex determining region-Y-related high mobility group box 2 (SOX2) have been identified as putative cancer stem-like cell/tumor-initiating cell markers in various cancer tissues. The aim of this study was to elucidate the prognostic impact of these putative cancer stem-like cell/tumorinitiating cell markers in upper urinary tract urothelial cell carcinoma. Immunohistochemical staining for ALDH1 and SOX2 was carried out on archival specimens from 125 patients with upper urinary tract urothelial cell carcinoma who underwent radical nephroureterectomy. The prognostic value of ALDH1 and SOX2 expression and other clinicopathological features was evaluated. On univariate analysis, tumor grade, pathological T stage, pathological N stage, lymphovascular invasion, ALDH1 expression and SOX2 expression were associated with a poor prognosis. On multivariate analysis, the independent factors of prognosis were tumor grade (P ¼ 0.014), pathological N stage (P ¼ 0.005) and ALDH1 expression (P ¼ 0.002). In subgroup analysis, those subgroups with no positive, one positive or two positive results in immunohistochemistry for ALDH1 and SOX2 expression had estimated 5-year cancer-specific survival rates of 80%, 49% and 22%, respectively (Po0.001). Neither ALDH1 nor SOX2 expression correlated with intravesical recurrence after radical nephroureterectomy. These findings suggest that cancer stem-like cells/tumor-initiating cells are linked to more aggressive behavior of upper urinary tract urothelial cell carcinoma, supporting the current cancer stem cell hypothesis. Thus, therapeutic targeting of cancer stem-like cells/tumor-initiating cells in upper urinary tract urothelial cell carcinoma is a future possibility.

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Aldehyde dehydrogenase 1 expression predicts poor prognosis in triple-negative breast cancer

Abstract: ALDH1 expression in carcinoma cells is an independent prognostic factor in TN breast cancer patients.

Cited by 74 publications

References 6 publications

Association of aldehyde dehydrogenase 1 expression and biologically aggressive features in breast cancer

Association of aldehyde dehydrogenase 1 expression and biologically aggressive features in breast cancer

Recent Progress in Triple Negative Breast Cancer Research

Prognostic impact of the expression of ALDH1 and SOX2 in urothelial cancer of the upper urinary tract

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