The Differential Expression of Cancer Stem Cell Markers CD44, CD24 and ALDH1 in Breast Cancer Histological Types

Aldehyde Dehydrogenase 1(ALDH-1) and CD44+CD24- are the most consistently used biomarkers to identify and characterize breast Cancer Stem Cells (CSCs). However, expression of CSCs in Specific Histologic Types (SHTs) of Invasive Ductal Carcinomas (IDCs) remains unclear. We aimed to determine the distribution of CD44, CD24 and ALDH-1 breast CSC markers in SHTs of IDC compared with that in IDC-Not Otherwise Specified (NOS). From October 2013 to February 2014, we analyzed 168 IDC cases for double immunohistochemical staining of CD44, CD24 and single expression of ALDH- 1. The distribution of these CSC markers, CD44+CD24-, ALDH-1 and CSC phenotypes (CD44+CD24-/ ALDH-1) were retrospectively evaluated among the distinct SHTs and intrinsic subtypes compared with IDC-NOS. Medullary, metaplastic and apocrine carcinomas enriched in ALDH-1 population (100%, 100%, and 66.7%, respectively, vs. 44.1% in IDC-NOS, P=0.04). Medullary, papillary, and metaplastic carcinomas displayed significant increases in CSC phenotype frequency (66.7%, 28.6% and 100%, respectively, vs. 20% in IDCNOS, P=0.03). In IDC-SHT, mucinous carcinoma was correlated with luminal A subtype and medullary, papillary, metaplastic, apocrine, and micropapillary carcinomas were correlated with triple negative breast cancer (P=0.01). CK5/6(+), EGFR(+), ER(-), PR(-), and high HG were associated with ALDH-1(+) or CSC phenotype, but HER2(-) was associated with CD44+CD24-(+). Within distinct SHTs, medullary and metaplastic carcinomas are highly associated with the basal-like subtype and the CSC phenotype. In conclusion, we demonstrated the described CD44+/CD24-, ALDH-1, and CSC phenotypes may identify CSCs with distinct levels of differentiation and several SHTs are distinguished entities from IDC-NOS with regard to CSC marker expression.