Clinicopathological signiﬁcance of cancer stem cell markers CD44
and ALDH1 expression in breast cancer
· Sonia Ziadi
· Hanene Saad
· Myriam Ben Dhiab
· Sarra Mestiri
· Mounir Trimeche
Received: 15 March 2018 / Accepted: 20 May 2018
© The Japanese Breast Cancer Society 2018
Background CD44 and aldehyde dehydrogenase 1 (ALDH1) has been reputed to be cancer stem cell (CSC) markers in
breast cancer. Yet, the clinicopathologic and prognostic signiﬁcance of these markers remain unclear. In this study, we have
investigated the expression of these markers and their relation with conventional clinicopathologic tumor characteristic
including molecular subtype.
Methods CD44 and ALDH1 expression were investigated by immunohistochemistry in a series of 157 formalin-ﬁxed
paraﬃn-embedded breast cancer tissues.
Results Overall, CD44 and ALDH1 are, respectively, detected in 33% (52 of 157) and 7% (10 of 157) of breast cancer
cases. We also observed that CD44 expression was associated with histological grade (p = 0.005). For ALDH1, we found
that its expression is more frequent with elderly women (> 50 years, p = 0.03). The investigation of relationship between the
stem cell phenotype and breast cancer molecular subtype, revealed that CD44 and ALDH1 expression was more frequent
in basal-like tumors (p = 0.005). Among the two cancer stem cell markers tested, ALDH1 showed a strong association with
the basal marker EGFR (p = 0.05).
Conclusions These ﬁndings suggest that CD44 and ALDH1 play a role in the clinical behavior in breast cancer and might
be interesting biomarkers and therapeutic targets.
Keywords CD44 · Aldehyde dehydrogenase 1 · Cancer stem cell · Breast cancer · Basal-like
Breast cancer is the principal cause of cancer death among
women, with more than 1,500,000 cases worldwide each
year . Breast cancer is a complex disease with a large het-
erogeneity, leading to highly variable clinical behavior and
response to therapy . However, the mechanisms resulting
in this heterogeneity in breast cancer are not well-understood
One possible explanation for the tumor heterogeneity is
the cancer stem cells. These cell subpopulations have the
capacity to self-renew and diﬀerentiate into multiple cell
types, and may contribute to drug resistance that promotes
tumor recurrence or metastasis . In breast cancer, cancer
stem cells are principally identiﬁable by the expression of
CD44 and ALDH1 .
CD44 is a class I transmembrane glycoprotein that serves
as the primary receptor for hyaluronan and binds other extra-
cellular matrix components, such as collagen, laminin, and
ﬁbronectin . This protein has been shown to promote
growth, invasion, and metastatic dissemination in breast
cancer cells [7, 8].
ALDH1, an enzyme responsible for the oxidation of
intracellular aldehydes, has been a subject of research focus
in recent years [9, 10]. Previous researches reported that
ALDH1 contributed to normal and tumor stem cell diﬀer-
entiation as well as invasion and metastasis in breast cancer
Based on recent information, it is evident to support the
use of the CD44 cell surface marker in combination with the
ALDH1 activity as an accurate method to identify cancer
stem cells within breast tumors .
Recently, many clinical studies have reported that tumors
expressing cancer stem cell markers are associated with
* Tahani Louhichi
Department of Pathology, Farhat-Hached Hospital,
4000 Sousse, Tunisia