In Situ Identification of CD44+/CD24− Cancer Cells in Primary Human Breast Carcinomas

Abstract

Breast cancer cells with the CD44+/CD24− phenotype have been reported to be tumourigenic due to their enhanced capacity for cancer development and their self-renewal potential. The identification of human tumourigenic breast cancer cells in surgical samples has recently received increased attention due to the implications for prognosis and treatment, although limitations exist in the interpretation of these studies. To better identify the CD44+/CD24− cells in routine surgical specimens, 56 primary breast carcinoma cases were analysed by immunofluorescence and confocal microscopy, and the results were compared using flow cytometry analysis to correlate the amount and distribution of the CD44+/CD24− population with clinicopathological features. Using these methods, we showed that the breast carcinoma cells displayed four distinct sub-populations based on the expression pattern of CD44 and CD24. The CD44+/CD24− cells were found in 91% of breast tumours and constituted an average of 6.12% (range, 0.11%–21.23%) of the tumour. A strong correlation was found between the percentage of CD44+/CD24− cells in primary tumours and distant metastasis development (p = 0.0001); in addition, there was an inverse significant association with ER and PGR status (p = 0.002 and p = 0.001, respectively). No relationship was evident with tumour size (T) and regional lymph node (N) status, differentiation grade, proliferative index or HER2 status. In a multivariate analysis, the percentage of CD44+/CD24− cancer cells was an independent factor related to metastasis development (p = 0.004). Our results indicate that confocal analysis of fluorescence-labelled breast cancer samples obtained at surgery is a reliable method to identify the CD44+/CD24− tumourigenic cell population, allowing for the stratification of breast cancer patients into two groups with substantially different relapse rates on the basis of CD44+/CD24− cell percentage.

Triple Negative Breast Tumors in African-American and Hispanic/Latina Women Are High in CD44+, Low in CD24+, and Have Loss of PTEN

“…Significantly shorter DFS in women with the CD44+/CD24- phenotype was reported in 4/9 studies, and is consistent with findings in this study (P=0.05). Notably, our study identified that the CD44+/CD24- phenotypes were significantly associated with TNBC (Table 2 and Table 3), which complement previous reports among other ethnic groups [26,27,34,36]. There is a plethora of data in the literature building a strong association of CD44+/CD24- with “cancer stem-cell (CSC) like” or “mesenchymal” phenotype [22,39-41].…”

TAZ is required for metastatic activity and chemoresistance of breast cancer stem cells

“…The relative abundance of CD44 þ /CD24 À /low cells in BC has an average of 6.12%. 12 Thus, following tumor sample dissociation, cell suspensions were maintained in specific culture conditions that allowed the expansion of undifferentiated cancer stem and progenitor cells, while negatively selecting serumdependent tumor and non-transformed accessory cells. [13][14][15] These cell cultures were essentially composed of the so-called tumor 'mammospheres' (Figure 1a) formed by a majority of CD44 þ / CD24…”

Evaluation of Breast Cancer Stem Cells and Intratumor Stemness Heterogeneity in Triple-negative Breast Cancer as Prognostic Factors

“…ALDH1+ phenotype was found to be associated with biological aggressiveness and poor outcomes of breast cancer 9, 16, 17. Notably, several reports indicated that CD44 + /CD24 - and ALDH1+ breast cancer cells were associated with TNBC subtype 18-21. CD133, a transmembrane glycoprotein, is a more recent BCSC marker identified to be correlated with prognosis in breast cancer.…”