The prognostic significance of ALDH1A1 expression in early invasive breast cancer

Althobiti, Maryam; El Ansari, Rokaya; Aleskandarany, Mohammed; Joseph, Chitra; Toss, Michael S.; Green, Andrew R.; Rakha, Emad A.

Abstract

Aims: Aldehyde dehydrogenase family 1 member A1 (ALDH1A1)is reportedly a key ALDH isozyme linked to the cancer stem cells (CSC) of many solid tumours, where it is involved in self-renewal, differentiation and self-protection. In this study, the prognostic significance of ALDH1A1 expression in early invasive breast cancer (BC) and its role as a BC stem cell (BCSC) were evaluated.

Methods: ALDH1A1 expression was assessed, using immunohistochemistry and tissue microarrays, in a large well- characterised BC cohort. ALDH1A1 mRNA expression was also assessed at the transcriptomic levels, utilising data from the Molecular Taxonomy of Breast Cancer International Consortium. The associations of ALDH1A1 with clinicopathological parameters, other stem cell markers and patient outcomes were determined.

Results: ALDH1A1 was expressed in 71% of BC cases, at both the protein and mRNA levels. High ALDH1A1 expression was associated with poor prognostic features, including high grade, poor Nottingham Prognostic Index (NPI), lymph node metastasis and highly proliferative ER+ (luminal B) and triple negative (TNBC) subtypes. ALDH1A1 expression was positively correlated with the expression of CD44, CD24, TWIST, SOX9, EPCAM and CD133. The high immunoexpression of ALDH1A1 was significantly associated with poor BC-specific survival [less than] 0.001), and specifically in the luminal B and TNBC subtypes (P=0.042 and P=0.003, respectively). The immunoexpression of ALDH1A1 was an independent predictor of poor prognosis (P=0.015).

Conclusions: ALDH1A1, as assessed using IHC, seems to act as a BCSC marker associated not only with other BCSC markers but also with poor prognostic characteristics and poor outcomes, particularly in the luminal B and TNBC subtypes.

Citation

Althobiti, M., El Ansari, R., Aleskandarany, M., Joseph, C., Toss, M. S., Green, A. R., & Rakha, E. A. (2020). The prognostic significance of ALDH1A1 expression in early invasive breast cancer. Histopathology, 77(3), 437-448. https://doi.org/10.1111/his.14129

• Journal Article Type: Article
• Acceptance Date: Mar 10, 2020
• Online Publication Date: May 5, 2020
• Publication Date: 2020-09
• Deposit Date: Mar 25, 2020
• Publicly Available Date: May 6, 2021
• Journal: Histopathology
• Print ISSN: 0309-0167
• Electronic ISSN: 1365-2559
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 77
• Issue: 3
• Pages: 437-448
• DOI: https://doi.org/10.1111/his.14129
• Keywords: Pathology and Forensic Medicine; Histology; General Medicine
• Public URL: https://nottingham-repository.worktribe.com/output/4202139
• Publisher URL: https://onlinelibrary.wiley.com/doi/abs/10.1111/his.14129?af=R