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Characteristic Genes in Luminal Subtype Breast Tumors with CD44+CD24–/Low Gene Expression Signature

Tsunoda Y.a, c · Sakamoto M.a, c · Sawada T.a · Sasaki A.b · Yamamoto G.b · Tachikawa T.b
Departments of aBreast Surgery and bDental Pathology, Showa University School of Medicine, Tokyo, and cBreast Center, Kameda Medical Center, Kamogawa, Japan Oncology 2011;81:336–344 (DOI:10.1159/000334690)

Abstract

Objective: Breast cancer cells with CD44+CD24–/low gene expression signature have been suggested to have stem cell-like tumor-initiating properties. The purpose of this study is to clarify the gene expression profiling of cells with CD44+CD24–/low gene expression signature in the luminal subtype. Methods: Laser capture microdissection was used to select the isolation of cancer cells in 35 frozen tissues of breast cancer, and RNA extracted from these cells was examined by real-time RT-PCR to quantify CD44 and CD24 expressions. Human stem cell RT2 Profiler PCR Array was used for gene expression analysis in the groups of CD44+CD24–/low and CD44+CD24+ gene expression signature. Results: Thirty-five tumors were divided into 3 groups. Group A was composed of the CD44+CD24–/low type, in which the ratio of CD44/CD24 was >10.0. Group B was composed of the CD44+CD24+ type, in which the ratio was >0.1 and ≤10.0. In group C, composed of the CD44–/lowCD24+ type, the ratio was <0.1. The number of tumors in groups A, B, and C were 5, 28, and 2, respectively. Regarding the correlation of CD44/CD24 status with tumor characteristics, the tumors of group A were significantly associated with axillary lymph node metastasis compared with those of group B (p = 0.033). There were no significant differences in tumor size, nuclear grade, or HER2 status between the two groups. According to signaling pathways, the number of expression genes for the Notch pathway in group A was significantly greater than in group B (p = 0.028). Overexpressed genes for ALDH1 (p = 0.021) and SOX2 (p = 0.018) were noted in group A compared to group B. Conclusion: This study suggests that the Notch pathway may be an important signaling pathway in luminal subtype with CD44+CD24–/low gene expression signature. In addition, either ALDH1 or SOX2 may be a candidate marker for cancer stem cells in luminal subtype breast cancer.

 

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