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

João Paulo Oliveira-Costa1, Juliana S Zanetti1, Giórgia G Silveira1, Danilo F Soave1, Lucinei R Oliveira1, Verônica A Zorgetto1, Fernando A Soares2, Sérgio Zucoloto1 and Alfredo Ribeiro-Silva13*

Author affiliations

1 Department of Pathology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil

2 Department of Pathologic Anatomy, A. C. Camargo Cancer Hospital, Brazil

3 Department of Pathology, Ribeirão Preto Medical School, University of São Paulo, Avenida Bandeirantes 3900, Bairro Monte Alegre, 14049-900, Ribeirão Preto, São Paulo, Brazil

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Citation and License

Diagnostic Pathology 2011, 6:73  doi:10.1186/1746-1596-6-73

Published: 8 August 2011

Abstract

Background

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 tumor. Stem cells renewal and differentiation can be directly influenced by the oxygen levels of determined tissues, probably by the reduction of oxidative DNA damage in hypoxic regions, thus leading to a friendlier microenvironment, regarding to clonal expansion and for resistance to chemotherapeutic regimens. Furthermore, there have been strong data indicating a pivotal role of hypoxic niche in cancer stem cells development. There are evidence that hypoxia could drive the maintenance of CSC, via HIF-1α expression, but it still to be determined whether hypoxia markers are expressed in breast tumors presenting CD44+CD24-/low immunophenotype.

Methods

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).

Results

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).

Conclusion

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.

Keywords:
breast cancer; CD44; CD24; HIF-1α; hypoxia; immunohistochemistry; prognosis; stem cell