B51
STAC2 expression predicts worse outcome in basal-like breast cancer
Wendy Hale1, James Carr1, Emad Rakha1, Graham Ball2, Sarah Watts1, Claire Paish1, Carlos Caldas3, Ian Ellis1, Andy Green1
1University of Nottingham and Nottingham Hospitals NHS Trust, UK, 2Nottingham Trent University, UK, 3Cancer Research UK Cambridge Research Institute, UK
Background
Basal-like cancers (BP) have attracted attention as a poor prognostic class of breast cancer. However, BP appear to encompass biologically and clinically heterogeneous tumours.
Method
In order to refine BP definition, we analysed over 47,000 gene transcripts in 132 invasive breast carcinomas using ANN analysis and identified three novel genes (SUPT5H, STAC2, PRL3) significantly associated with BP (cytokeratin(CK)5/6 and/or CK14 positive). Using a large invasive breast carcinoma cohort (n=2000), prepared as TMAs, we assessed these targets immunohistochemically and investigated associations with clinicopathological variables, patients outcome and ability to refine BP classification.
Results
Cytoplasmic STAC2 protein expression was associated with lower tumour grade (p<0.001) but not with stage, VI, or size. STAC2 was associated with CK14 (p=0.025), but not CK5/6 or BP, and a shorter breast cancer specific survival (BCSS;p=0.042). STAC2 positive BP tumours had a significantly shorter BCSS and disease-free survival (DFS) compared with STAC2 negative BP tumours, independent of grade, size and stage (p<0.01). Nuclear SUPT5H protein expression was associated with BP (p<0.001) but not other clinicopathological variables or patient outcome. PRL3 protein expression was not associated with BP or patient outcome.
Conclusion
This study confirms the biological and clinical heterogeneity of the BP and the difficulties in translating global gene expression data into routine practice using IHC. We have identified a novel subgroup of BP showing STAC2 expression that have significantly worse clinical outcome. Further studies analysing the role of STAC2 are therefore warranted.
