Differential expression of HIF-1 alpha in CD44(+)CD24(-/) (low) breast ductal carcinomas

Autor(es)

Oliveira-Costa, Joao Paulo ^[1] ; Zanetti, Juliana S. ^[1] ; Silveira, Giorgia G. ^[1] ; Soave, Danilo F. ^[1] ; Oliveira, Lucinei R. ^[1] ; Zorgetto, Veronica A. ^[1] ; Soares, Fernando A. ; Zucoloto, Sergio ^[1] ; Ribeiro-Silva, Alfredo ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Pathol, Ribeirao Preto Med Sch, BR-14049900 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: DIAGNOSTIC PATHOLOGY; v. 6, AUG 8 2011.
• Citações Web of Science: 17

Resumo

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-1 alpha 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-1 alpha (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. (AU)

• Processo FAPESP: 08/06461-1 - O papel da hipóxia tumoral na fisiopatogênese dos carcinomas mamários de imunofenótipo CD44+CD24-
• Beneficiário: Alfredo Ribeiro da Silva
• Linha de fomento: Auxílio à Pesquisa - Regular
• Processo FAPESP: 10/08400-0 - Identificação de padrões moleculares relacionados ao desenvolvimento do carcinoma epidermóide oral utilizando a tecnologia de micro-arranjos de cDNA
• Beneficiário: João Paulo Oliveira da Costa
• Linha de fomento: Bolsas no Brasil - Doutorado