CD44+/CD24- phenotype contributes to malignant relapse following surgical resection and chemotherapy in patients with invasive ductal carcinoma

Abstract

BackgroundInvasive ductal carcinoma is the most common type of breast malignancy, with varying molecular features and resistance to treatment. Although CD44+/CD24- cells are believed to act as breast cancer stem cells and to be linked to poor prognosis in some patients, the association between these cells and tumor recurrence or metastasis in all or some types of invasive ductal carcinoma is unclear.MethodsA total of 147 randomly selected primary and secondary invasive ductal carcinoma samples were assayed for expression of CD44, CD24, ER, PR, and Her2. The association between the proportions of CD44+/CD24- tumor cells and the clinico-pathological features of these patients was evaluated.ResultsCD44+/CD24- tumor cells were detected in 70.1% of the tumors, with a median proportion of 5.8%. The proportion of CD44+/CD24- tumor cells was significantly associated with lymph node involvement (P = 0.026) and PR status (P = 0.038), and was correlated with strong PR status in patients with recurrent or metastatic tumors (P = 0.046) and with basal-like features (p = 0.05). The median disease-free survival (DFS) of patients with and without CD44+/CD24-/low tumor cells were 22.9 ± 2.2 months and 35.9 ± 3.8 months, and the median overall survival (OS) of patients with and without CD44+/CD24-/low tumor cells were 39.3 ± 2.6 months and 54.0 ± 3.5 months, respectively, and with both univariate and multivariate analyses showing that the proportion of CD44+/CD24-/low tumor cells was strongly correlated with DFS and OS.ConclusionThe prevalence of CD44+/CD24- tumor cells varied greatly in invasive ductal carcinomas, with the occurrence of this phenotype high in primary tumors with high PR status and in secondary tumors. Moreover, this phenotype was significantly associated with shorter cumulative DFS and OS. Thus, the CD44+/CD24- phenotype may be an important factor for malignant relapse following surgical resection and chemotherapy in patients with invasive ductal carcinoma.

Prognostic Implication of Urothelial Stem Cell Markers Differs According to Primary Tumour Location in Non-Muscle-Invasive Bladder Cancer

“…For example, CD44+/CD24-appear to an independent indicator of tumor invasiveness and recurrence in breast cancer [29], while CD44+/CD24-expression varied between breast cancer cell lines and between primary tumors, and it was not universally enriched in breast cancer stem cells [30]. Similarly, ALDH1A1 expression is strongly associated with prognosis in patients with lung adenocarcinoma, while its expression in papillary predominant adenocarcinoma was significantly higher than those of solid predominant adenocarcinoma [31].…”

Expression of Novel CD44st and MMP2 in NSCLC Tissues and Their Clinical Significance

“…Some abnormally expressed CD44 receptors bind hyaluronan, which promotes the secretion of matrix metalloproteinases (MMPs), resulting in extracellular matrix degradation which is closely associated with tumor angiogenesis, axillary lymph node metastasis, and prognosis [21][22][23]. It has been reported that during tumor progression, hyaluronan binds to CD44 isoforms which are extensively expressed on the surface of the cell membrane, and mediates the activation of ankyrin and Rho small G protein, further activating the PI3K-AKT signaling pathway.…”

Doxorubicin induces drug resistance and expression of the novel CD44st via NF-κB in human breast cancer MCF-7 cells

“…The CD44 + CD24 -phenotype was found to be significantly associated with lymph node involvement, progesterone receptor status in patients with recurrent or metastatic tumors, the phenotype of triple-negative breast cancer, and disease-free and overall survival of patients. It was therefore considered that the CD44 + CD24 -phenotype may be an important factor associated with malignant relapse following surgical resection and chemotherapy in patients with invasive ductal carcinoma (22).…”

“…The binding of various abnormally expressed CD44 molecules to the receptor HA promotes the secretion of MMPs, resulting in ECM degradation, which is closely associated with axillary lymph node metastasis, increased angiogenesis, prognosis and drug resistance (17)(18)(19)(20)(21)(22). It has been shown that HA binds to the CD44 variant that is widely distributed on the surface of the cell membrane during tumor progression, which induces the activation of ankyrin and small G-protein Rho, and the activation of the PI3K-AKT signaling pathway, thereby leading to enhanced tumor cell adhesion, growth, migration and invasion, and resultant tumor progression (23).…”