Role of DYRK2 in invasive ductal carcinoma of the breast


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Jean Quinn1,Phungern Khongthong1,Donald McMillan1,Laureano de la Vega2,Joanne Edwards1
1university of glasgow,2university of Dundee

Abstract

Background

Breast cancer is the most commonly diagnosed cancer in women in the UK with around 55,000 women being diagnosed each year. Of the subtypes invasive ductal carcinoma (IDC) is the most common (70-80%), triple negative disease (TN) has 5 years survival of 77% compared to 92% for women with other subtypes.

Dual specificity tyrosine-phosphorylation-regulated kinase 2 (DYRK2) is one of a family of proteins that function as integrators of stress signals and can modulate different downstream pathways which allow cells to cope with stress signals such as hypoxia and DNA damage. Additionally, it has been shown to have a role in epithelial-mesenchymal transition(EMT) suggesting a role in metastasis. Studies have shown that DYRK2 can play a dual role in cancer by either inducing apoptosis or promoting cell survival.

Method

Immunohistochemistry was employed to investigate if cytoplasmic and/or nuclear  expression of DYRK2 was associated with clinical outcome measures in a cohort of 270 patients. Expression was determined using the weighted histoscore method.  Antibody specificity was confirmed in paraffin embedded cell pellets +/- DYRK2 silencing.

Results

High cytoplasmic expression was significantly associated with increasing tumour size (P=0.017), tumour grade (P=0.002), decreasing inflammation (P=0.012), ER (P<0.001), PR (<0.001) and molecular subtype (P<0.001). High nuclear expression was significantly associated with increasing tumour size (P=0.018), tumour grade(P=0.018), proliferation (P=0.045), decreasing inflammation (P=0.004), ER (P<0.001), PR (P=0.02) and molecular subtype (P=0.002).  High expression of DYRK2 in both the cytoplasm and nucleus was associated with shorter cancer specific survival (CSS) although this did not reach significance (P=0.28).  When stratified by molecular subtype expression of DYRK2 was associated with shorter CSS in TN breast cancer and improved CSS in HER2 enriched breast cancer.   

Conclusion

In a small cohort of breast cancer patients, DYRK2 expression significantly correlated with adverse clinic-pathological features in TN breast cancer.