The relationship between phosphorylation status of focal adhesion kinases, molecular subtypes, tumour microenvironment and survival in patients with primary operable ductal breast cancer.

Background: Despite advances in therapies to treat breast cancer, over 100,000 patients die in the UK of this disease per year, highlighting the need to develop effect predictive and prognostic markers for patients with primary operable ductal breast cancer. Therefore, the aim of the present study was to examine the relationship between membranous, cytoplasmic and nuclear expression of focal adhesion kinase (phosphorylated at Y 397, Y 861 and Y 925), molecular subtypes, tumour microenvironment and survival in patients with primary operable ductal breast cancer.

Methods: Four hundred and seventy-four patients presenting between 1995 and 1998 with primary operable ductal breast cancer were included in this study. Using tissue microarrays expression of membranous, cytoplasmic and nuclear tumour cell phosphorylation of FAK at Y, Y and Y was assessed, and associations with clinicopathological characteristics, tumour microenvironment and cancer-specific survival (CSS) were examined.

Results: No significant association was observed for ph-FAK Y with survival at all sites. However, high expression of membranous ph-FAK Y was associated with increased tumour grade (P < .001), molecular subtypes (P < .001), increased tumour necrosis (P < .001), high Klintrup-Mäkinen grade (P < .001), increased CD138+ plasma cells (P = .031), endocrine therapy (P = .001) and poor cancer specific survival (P = .040). Similarly, high expression of nuclear ph-FAK Y was associated with decreased age (P = .042), increased CD138+ plasma cells (P = .001) and poor cancer specific survival (P = .003). Furthermore, high expression of cytoplasmic ph-FAK Y was associated with decreased tumour grade (P < .001), less involved lymph node (P = .020), molecular subtypes (P < .001), decreased tumour necrosis (P < .001), low Klintrup-Mäkinen grade (P < .001), decreased CD4+ T-cells (P = .006), decreased CD138+ plasma cells (P = .034), endocrine therapy (P < .001), chemotherapy (P = .048), and improved cancer specific survival (P = .044). On multivariate analysis, high expression of nuclear ph-FAK Y was independently associated with reduced cancer specific survival (P = .017).

Conclusion: The results of the present study show that membranous and nuclear ph-FAK Y and cytoplasmic ph-FAK Y were associated with prognosis in patients with primary operable ductal breast cancer. In addition, high expression of nuclear ph-FAK Y was an independent prognostic factor in patients with primary operable ductal breast cancer and could be incorporated into clinical practice.