INTRODUCTION. Hormone receptor (HR)-positive breast cancer is characterised by the presence of oestrogen receptor (ER) and progesterone receptor (PR). The hook-related protein (HkRP) family traditionally function as microtubule to organelle linker proteins but have also recently been found to have a role in cancer metastasis and immunity. The HkRP family consists of: Girdin (HkRP1), Daple (HkRP2) and Gipie (HkRP3). We endeavoured to determine whether the expression and localisation of HkRPs in HR-positive breast cancer specimens was correlated with certain clinical characteristics which impact the patient’s clinical staging and resultant therapeutic strategy.
METHODS. 238 patients underwent surgical resection for ER-positive, HER2-negative breast cancer and had metastatic deposits of tumour greater than 2.0mm within axillary lymph nodes. Primary tumours were assembled into tissue microarrays (TMAs) were stained for Girdin, Daple and Gipie. TMAs were analysed via immunohistochemistry (IHC) and immunofluorescence (IF). IHC was independently H-scored by a senior Pathologist. IF was localised by senior scientists specialised in subcellular localisation. These results were then compared to a patient database detailing various clinicopathological parameters.
RESULTS. We have demonstrated that, in HR-positive breast cancer with axillary nodal metastasis, the localisation of the HkRPs differs from healthy tissue. We have noted that the expression of Daple and Gipie in distinct subcellular locations is associated with larger tumour size. In addition, the expression of Gipie in specific a subcellular location is associated with a considerable increase in number of lymph node metastases.
CONCLUSION. This research presents the HkRP family as potential novel biomarkers for the identification of clinically aggressive HR-positive breast cancer. This could have a useful application at initial biopsy, to assist in predicting patients who are at higher risk of advanced clinical staging and thus influence clinical decision making.