Prognostic value of aldehyde dehydrogenase 1 (ALDH1) in invasive breast carcinomas.

Hale Demir,Sennur Ilvan,Hande Turna,Bugra Taygun Gulle,Ozgecan Dulgar

doi:10.17305/bjbms.2018.3094

Hale Demir, Sennur Ilvan + Show 3 more

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https://doi.org/10.17305/bjbms.2018.3094

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Abstract

Aldehyde dehydrogenase 1 (ALDH1) has been identified as a marker of cancer stem cells in breast cancer (BC). Recent studies showed that ALDH1 expression is correlated with poor prognostic parameters and worse clinical outcome in BC. We evaluated ALDH1 expression by immunohistochemistry in a series of 217 invasive BCs and investigated the correlation between ALDH1 expression and clinicopathological parameters, molecular subtypes (luminal A, luminal B, human epidermal growth factor receptor 2 [HER2] type, and triple-negative BC [TNBC]), and patient survival. There was a significant association between ALDH1 expression and tumor grade (p < 0.001), i.e., the expression of ALDH1 was higher in high-grade tumors. ALDH1 expression was significantly associated with estrogen and progesterone receptor (ER and PR) negativity (p < 0.001) and HER2 positivity (p = 0.001). ALDH1 expression ratios were higher in HER2 type and TNBC. There was a statistically significant correlation between ALDH1 negativity and luminal A subtype (p < 0.001). The overall and disease free survival were shorter in ALDH1+ tumors, although without statistical significance. We confirm that ALDH1 is a potentially important, poor prognostic factor in BC, associated with high histological grade, ER/PR negativity and HER2 positivity. For more accurate results, ALDH1 expression should be evaluated in larger case series including various types/subtypes of BC.

Highlights

Breast cancer (BC) is one of the most common malignant tumors in women worldwide
To contribute to the ongoing efforts in this field, we investigated the association of Aldehyde dehydrogenase 1 (ALDH1) expression with clinicopathological parameters and survival in a sample of invasive BCs
ALDH1: Aldehyde dehydrogenase 1; MF/MC: Multifocality/multicentricity; NOS: Not otherwise specified; estrogen receptor (ER): Estrogen receptor; progesterone receptor (PR): Progesterone receptor; higher epidermal growth factor receptor 2 (HER2): Human epidermal growth factor receptor 2; triple-negative BC (TNBC): Triple‐negative breast cancer. *For statistical analysis, 4 cases with unknown lymph node status were ignored and, due to the low number of cases, the remaining 213 cases were divided into two groups according to lymph node status. **p

Summary

Introduction

Breast cancer (BC) is one of the most common malignant tumors in women worldwide. Cancer stem cells (CSCs) are a subpopulation of cells within tumors that have features similar to normal stem cells, i.e., CSCs have the ability to self-renew and differentiate into mature cancer cells through asymmetric cell divisions. These cells are characterized by dysregulated gene expression and altered signaling pathways, and have been implicated in the onset, maintenance, recurrence and distant metastasis of tumors, as well as tumor resistance to therapy. ALDH1A1 is a highly conserved cytosolic isozyme, in addition to the other two cytosolic isotypes ALDH1A2 and ALDH1A3, and is able to catalyze the oxidation of retinal (vitamin A aldehyde) to retinoic acid (RA) which regulates gene expression and is important for normal development and maintenance of adult organs and tissues [6]

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