The role of ALDH1A1 in contributing to breast tumour aggressiveness: A study conducted in an African population

Eric Gyan; Andrew Green; Linda Ahenkorah-Fondjo; Andrew Jackson; Michael S Toss; Patrick Kafui Akakpo; Leonard Derkyi-Kwarteng; Ganiyu A Rahman; William Owiredu

doi:10.1016/j.anndiagpath.2020.151696

The role of ALDH1A1 in contributing to breast tumour aggressiveness: A study conducted in an African population

Ann Diagn Pathol. 2021 Apr:51:151696. doi: 10.1016/j.anndiagpath.2020.151696. Epub 2021 Jan 14.

Authors

Eric Gyan¹, Andrew Green², Linda Ahenkorah-Fondjo³, Andrew Jackson², Michael S Toss², Patrick Kafui Akakpo⁴, Leonard Derkyi-Kwarteng⁴, Ganiyu A Rahman⁵, William Owiredu³

Affiliations

¹ University of Nottingham, Division of Cancer and Stem Cells, School of Medical Sciences, Nottingham, UK; Kwame Nkrumah University of Science and Technology, Department of Molecular Medicine, School of Medical Sciences, Kumasi, Ghana; University of Cape Coast, Department of Pathology, School of Medical Sciences, Cape Coast, Ghana; University of Health and Allied Sciences, School of Medicine, Department of Pathology, Ho, Ghana. Electronic address: mzxeg2@nottingham.ac.uk.
² University of Nottingham, Division of Cancer and Stem Cells, School of Medical Sciences, Nottingham, UK.
³ Kwame Nkrumah University of Science and Technology, Department of Molecular Medicine, School of Medical Sciences, Kumasi, Ghana.
⁴ University of Cape Coast, Department of Pathology, School of Medical Sciences, Cape Coast, Ghana.
⁵ University of Cape Coast, Department of Surgery, School of Medical Sciences, Cape Coast, Ghana.

PMID: 33460998
DOI: 10.1016/j.anndiagpath.2020.151696

Abstract

Aldehyde dehydrogenase 1 member A1 (ALDH1A1) is one of the most well studied breast cancer stem cells. Its expression has been associated with poor clinicopathological features and clinical outcomes in several studies. This paper studies the expression of ALDH1A1 and its combination with CD44⁺/CD24^-/low breast cancer stem cell and their association with clinicopathological parameters and molecular subtypes.

Method: Tissue Microarray was constructed from 222 Formalin Fixed Paraffin Embedded (FFPE) breast cancer tissues. The expression of ALDH1A1, CD44 and CD24 were assessed by Immunohistochemistry (IHC). The association of ALDH1A1 and its association with clinicopathological parameters, molecular subtypes, CD44 and CD24 were studied in an African population. The association between CD44⁺/CD24^-/low/ALDH1⁺ and the clinicopathological phenotypes were also studied.

Results: A high ALDH1A1 expression of 90% was recorded in this study. No association was found between ALDH1A1 and clinicopathological parameters. ALDH1A1 was positively associated with CD24 (r = 0.228, OR-4.599 95% CI- 1.751-12.076, p = 0.001) and CD44 (r = 0.228, OR-5.538 95%CI- 1.841-16.662, p = 0.001) but not associated with CD44⁺/CD24^-/low (r = 0.134, OR- 2.720 95%CI- 0.959-7.710, p = 0.052). CD44⁺/CD24^-/ALDH1⁺ however had significant associations with Age (p- 0.020, r = 0.161, OR- 2.771, 95%CI 1.147-6.697), Gender (p = 0.004, OR- 15.333 95%CI 1.339-175.54), Tumour grade (p = 0.005, r = 0.197, OR-3.913 95%CI 1.421-10.776) and clinical prognostic staging (p = 0.014, r = 0.182, OR-3.028 95%CI- 1.217-7.536). There was no association between CD44⁺/CD24^-/ALDH1⁺ and the molecular subtypes.

Conclusion: The high expression of ALDH1A1 in breast cancer makes it an important target for targeted therapy. This study further confirms the increased tumourigenicity of CD44⁺/CD24^-/ALDH1⁺ combination phenotype and its association with increased tumour grade and clinical prognostic stage. Survival studies of ALDH1A1 and other breast cancer stem cells in African populations are strongly recommended to help further understand their effect on tumour aggressiveness.

Keywords: ALDH1; Africans; Breast cancer; CD24; CD44; Immunohistochemistry; Prognosis.

MeSH terms

Aldehyde Dehydrogenase 1 Family / metabolism*
Black People / ethnology
Black People / genetics
Breast Neoplasms / metabolism*
Breast Neoplasms / pathology*
CD24 Antigen / metabolism
Female
Ghana / epidemiology
Humans
Hyaluronan Receptors / metabolism
Immunohistochemistry / methods
Male
Middle Aged
Neoplasm Grading / methods
Neoplasm Invasiveness / pathology*
Neoplastic Stem Cells / metabolism*
Prognosis
Retinal Dehydrogenase / metabolism*
Retrospective Studies
Severity of Illness Index
Tissue Array Analysis / methods

Substances

CD24 Antigen
CD24 protein, human
CD44 protein, human
Hyaluronan Receptors
Aldehyde Dehydrogenase 1 Family
ALDH1A1 protein, human
Retinal Dehydrogenase