Abstract
The RUNX1 transcription factor is widely recognised for its tumour suppressor effects in leukaemia. Recently a putative link to breast cancer has started to emerge, however the function of RUNX1 in breast cancer is still unknown. To investigate if RUNX1 expression was important to clinical outcome in primary breast tumours a tissue microarray (TMA) containing biopsies from 483 patients with primary operable invasive ductal breast cancer was stained by immunohistochemistry. RUNX1 was associated with progesterone receptor (PR)-positive tumours (P<0.05), more tumour CD4+(P<0.05) and CD8+(P<0.01) T-lymphocytic infiltrate, increased tumour CD138+plasma cell (P<0.01) and more CD68+macrophage infiltrate (P<0.001). RUNX1 expression did not influence outcome of oestrogen receptor (ER)-positive or HER2-positive disease, however on univariate analysis a high RUNX1 protein was significantly associated with poorer cancer-specific survival in patients with ER-negative (P<0.05) and with triple negative (TN) invasive breast cancer (P<0.05). Furthermore, multivariate Cox regression analysis of cancer-specific survival showed a trend towards significance in ER-negative patients (P<0.1) and was significant in triple negative patients (P<0.05). Of relevance, triple negative breast cancer currently lacks good biomarkers and patients with this subtype do not benefit from the option of targeted therapy unlike patients with ER-positive or HER2-positive disease. Using multivariate analysis RUNX1 was identified as an independent prognostic marker in the triple negative subgroup. Overall, our study identifies RUNX1 as a new prognostic indicator correlating with poor prognosis specifically in the triple negative subtype of human breast cancer.
Highlights
Breast cancer is the third most common cause of cancer death in the UK, accountable for more than 11,000 deaths in 2011 alone and an estimated 39,620 female deaths in the USA in 2013
These results suggest that RUNX1 expression could be dysregulated in human breast cancer
RUNX1 expression in the tumour epithelium was determined by histoscore which takes into account the percentage of positive signal and staining intensity
Summary
Breast cancer is the third most common cause of cancer death in the UK, accountable for more than 11,000 deaths in 2011 alone (www.cancerresearchuk.org) and an estimated 39,620 female deaths in the USA in 2013 (www.cancer.gov). Oestrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) are wellestablished prognostic and predictive markers, and testing for them is considered standard of care [1]. Based on the receptor status, human breast cancer can be subdivided into three main groups: oestrogen receptor positive (ER+), human epidermal growth factor receptor 2 positive (HER2+) and triple negative (ER2/PR2/HER2–). The triple negative (TN) subtype lacks any specific targeted therapy and is associated with worse overall prognosis in comparison with the other subtypes [3]. This underlines the urgent need for new prognostic and therapeutic targets specific for this group of patients
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