Poster Presentation 14th International Biennial Conference on Metastasis Research 2012

Can Dicer explain decreased microRNA expression in lymph node metastases of triple negative breast cancer? (#64)

Kelly A Avery-Kiejda 1 , Stephen G Braye 2 , John F Forbes 3 4 , Rodney J Scott 1 2
  1. Hunter Medical Research Institute, University of Newcastle, New Lambton Heights , NSW, Australia
  2. Hunter Area Pathology Service, John Hunter Hospital, New Lambton Heights, NSW, Australia
  3. Australian New Zealand Breast Cancer Trials Group, Department of Surgical Oncology, Calvary Mater Newcastle Hospital, Waratah, NSW, Australia
  4. School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia

Breast cancer is the most common malignancy that develops in women, responsible for the highest cancer-related death rates worldwide. Triple negative breast cancers represent a clinically important breast cancer subtype that have an aggressive clinical phenotype, are associated with a higher likelihood of metastasis and are not responsive to current targeted therapies. miRNAs have emerged as an attractive candidate for biomarkers and treatment targets in breast cancer, but their role in the progression of triple negative breast cancer remains largely unexplored. In addition, reduced expression of the enzyme responsible for miRNA production, Dicer, has been associated with shorter metastasis-free survival in breast cancer and with the triple negative subtype. However, the role of Dicer in the progression of triple negative breast cancer is unknown.

Our previous results have shown that the repertoire of miRNAs expressed in lymph node negative and lymph node positive breast cancers are largely distinct from one another. In particular, miRNA profiles associated with lymph node negativity tended to be up-regulated, while those associated with lymph node positivity were down-regulated and largely overlapped with the profiles of their matched lymph node metastases. This study has investigated if Dicer expression is altered in the progression of triple negative breast cancer from normal to primary breast cancer to lymph node metastases. For this analysis, we have examined the mRNA expression of Dicer by real-time PCR in 31 primary triple negative breast cancers (with known lymph node status) and in 13 matched lymph node metastases compared with 23 matched normal breast tissues. The results of this study are currently being analysed and will be presented. This study will provide novel insight into the regulation of miRNAs that contribute to the progression of a triple negative breast cancer to a metastasis.