Open Access Highly Accessed Research article

Tumour-associated endothelial-FAK correlated with molecular sub-type and prognostic factors in invasive breast cancer

Annika N Alexopoulou1, Colan M Ho-Yen2, Vassilis Papalazarou3, George Elia2, J Louise Jones2 and Kairbaan Hodivala-Dilke1*

Author Affiliations

1 Adhesion and Angiogenesis Laboratory, Centre for Tumour Biology, Barts Cancer Institute – a CR-UK Centre of Excellence, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK

2 Breast Group, Centre for Tumour Biology, Barts Cancer Institute – a CR-UK Centre of Excellence, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK

3 Vascular Adhesion Lab, BSRC Al. Fleming, 34 Fleming str., 166 72 Vari Athens, Greece

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BMC Cancer 2014, 14:237  doi:10.1186/1471-2407-14-237

Published: 2 April 2014

Abstract

Background

Breast cancer is a heterogeneous disease that can be classified into one of 4 main molecular sub-types: luminal A, luminal B, Her2 over-expressing and basal-like (BL). These tumour sub-types require different treatments and have different risks of disease progression. BL cancers can be considered a sub-group of Triple negative (TN) cancers since they lack estrogen (ER), progesterone (PR) and Her2 expression. No targeted treatment currently exists for TN/BL cancers. Thus it is important to identify potential therapeutic targets and describe their relationship with established prognostic factors. Focal adhesion kinase (FAK) is upregulated in several human cancers and also plays a functional role in tumour angiogenesis. However, the association between breast cancer sub-types and tumour endothelial-FAK expression is unknown.

Methods

Using immunofluorescence, we quantified FAK expression in tumour endothelial and tumour cell compartments in 149 invasive breast carcinomas and correlated expression with clinical, pathological and molecular parameters.

Results

Low endothelial-FAK expression was independently associated with luminal A tumours at univariate (p < 0.001) and multivariate (p = 0.001) analysis. There was a positive correlation between FAK expression in the vascular and tumour cell compartments (Spearman’s correlation co-efficient = 0.394, p < 0.001). Additionally, endothelial and tumour cell FAK expression were significantly increased in TN tumours (p = 0.043 and p = 0.033 respectively), in tumours with negative ER and PR status, and in high grade tumours at univariate analysis.

Conclusion

Our findings establish a relationship between endothelial-FAK expression levels and the molecular sub-type of invasive breast cancer, and suggest that endothelial-FAK expression is potentially more clinically relevant than tumour cell FAK expression in breast cancer.

Keywords:
FAK; Endothelium; Breast cancer; Molecular sub-type