title: Expression of RUNX1 correlates with poor patient prognosis in triple negative breast cancer.
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.
authors: Transgenic Models Lab, Cancer Research UK Beatson Institute, Glasgow, Scotland, United Kingdom.
authors: Nicola
authors: N
authors: Ferrari
authors: Academic Unit of Surgery, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom.
authors: Zahra M A
authors: ZM
authors: Mohammed
authors: Transgenic Models Lab, Cancer Research UK Beatson Institute, Glasgow, Scotland, United Kingdom.
authors: Colin
authors: C
authors: Nixon
authors: Transgenic Models Lab, Cancer Research UK Beatson Institute, Glasgow, Scotland, United Kingdom.
authors: Susan M
authors: SM
authors: Mason
authors: University Pathology Unit, Southern General Hospital, Glasgow, Scotland, United Kingdom.
authors: Elizabeth
authors: E
authors: Mallon
authors: Academic Unit of Surgery, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom.
authors: Donald C
authors: DC
authors: McMillan
authors: School of Veterinary Medicine, University of Glasgow, Glasgow, Scotland, United Kingdom.
authors: Joanna S
authors: JS
authors: Morris
authors: School of Veterinary Medicine, University of Glasgow, Glasgow, Scotland, United Kingdom.
authors: Ewan R
authors: ER
authors: Cameron
authors: Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom.
authors: Joanne
authors: J
authors: Edwards
authors: Transgenic Models Lab, Cancer Research UK Beatson Institute, Glasgow, Scotland, United Kingdom.
authors: Karen
authors: K
authors: Blyth
mesh_terms: D045744:Cell Line, Tumor; D050676:Core Binding Factor Alpha 2 Subunit / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D011379:Prognosis; D011960:Receptors, Estrogen / Q000378:metabolism; D064726:Triple Negative Breast Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D011960:Receptors, Estrogen