Differential expression of HIF-1α in CD44+CD24-/low breast ductal carcinomas

Immunohistochemical analysis of CD44+CD24-/low expression and its relationship with hypoxia markers and clinical outcome were evaluated in 253 samples of breast ductal carcinomas. Double-immunolabeling was performed using EnVision Doublestain System (Dako, Carpinteria, CA, USA). Slides were then scanned into high-resolution images using Aperio ScanScope XT and then, visualized in the software Image Scope (Aperio, Vista, CA, USA).In univariate analysis, CD44+CD24-/low expression showed association with death due to breast cancer (p = 0.035). Breast tumors expressing CD44+CD24-/low immunophenotype showed relationship with HIF-1α (p = 0.039) and negativity for HER-2 (p = 0.013).Considering that there are strong evidences that the fraction of a tumour considered to be cancer stem cells is plastic depending upon microenvironmental signals, our findings provide further evidence that hypoxia might be related to the worse prognosis found in CD44+CD24-/low positive breast tumors.The cancer stem cell (CSC) hypothesis postulates that tumors are maintained by a self-renewing CSC population that is also capable of differentiating into non-self-renewing cell populations that constitute the bulk of the tumor [1]. The first insight indicating a role of breast cancer stem cells (BCSC) in breast carcinogenesis was demonstrated by the study of Al-Hajj and co-workers, where Lin-CD44+CD24-/low cells injected into the mammary fat pad of non-obese diabetic/severed combined immunodeficient (NOD/SCID) mice were able to form palpable tumors, even with just a few hundred of cells being transplanted. Another interesting observation in the same study was the fact that Lin-CD44+CD24-/low cells were not only able to give origin to additional Lin-CD44+CD24-/low cells, but also generated phenotypically distinct cells, indicating that BCSC could generate an homogeneous population of non-tumorigenic cells, besides the generation of new BCSC [2].Stem cells renewal and differentiation can be directly i