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.
Highlights
Invasive ductal carcinoma is the most common breast malignancy and a leading cause of cancer-related death in women worldwide.[1]
These cells had the phenotype of cancer cells during the epithelial to mesenchymal transition, [10] indicating that the gene expression pattern of CD44 +/CD24- cells in breast cancers resembled more closely the pattern observed in CD44+/CD24- cells in normal breast than that of CD44-/CD24+ cells isolated from the same tumor.[6]
Of the 147 patients, 87 (59.2%) were received adjuvant chemotherapy and 95 (64.6%) were received agents targeted against estrogen receptor
Summary
Invasive ductal carcinoma is the most common breast malignancy and a leading cause of cancer-related death in women worldwide.[1]. Hoechst dye efflux, and flow cytometry analysis of cell surface markers such as CD44, CD24, CD133, epithelial cell adhesion molecule, and mucin-1,[5] normal human breast stem-cell like cells have been independently identified as showing elevated expression of CD44 and no expression of CD24 (CD44 +/CD24-), as well as elevated levels of stem cell enriched genes.[6] The CD44+/CD24- subpopulation was believed to be putative stem cells in human breast tissue, enriched for basal cells and motility genes, which could be generated during the epithelial-mesenchymal transition These cells were negative for mucin 1, estrogen receptor (ER), and v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 (erbB2) receptor. 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
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