CK2α as a prognostic factor in invasive ductal carcinomas of the breast: cancer recurrence prognosis by surgical sampling

Breast cancer is the most common cancer in Japanese and Asian women. Although the 5-year survival rate of these patients is relatively high, recurrences and fatalities do occur. The objective of this work was to develop a reliable prognostic indicator to guide therapeutic intervention without waiting for recurrence or metastasis. We have previously shown that positive immunohistochemical staining of a protein kinase, CK2α (CSNK2A1), in nucleoli of invasive ductal carcinoma cells is strongly associated with tumour recurrence and poor patient outcomes. For this study, we did an immunohistochemistry investigation of the location of CK2α in the nuclei and nucleoli of formalin-fixed, paraffin-embedded tissue block samples from patients with invasive ductal carcinoma who underwent surgery in 2008–14 but no neoadjuvant chemotherapy at Hoshi General Hospital, Fukushima, Japan. Furthermore, a new study with 59 patients with luminal type breast cancer was done. Patients were followed-up (clinicopathological information and outcomes) for more than 5 years. To characterise CK2α-associated proteins systematically, nuclear and nucleolar extracts were prepared from MCF-7 cells and immunoprecipitated with anti-CK2α antibodies followed by nano-flow liquid chromatography mass spectrometry analysis. We did a Kaplan-Meier analysis to evaluate whether nucleolar CK2 staining might be associated with poor recurrence-free survival. This retrospective study was approved by the Institutional Review Boards of Fukushima Medical University and Hoshi General Hospital. Samples from 112 patients were included. 105 (94%) of 112 patients with invasive ductal carcinoma had high CK2α expression in nuclei, and 41 (37%) of 112 displayed it predominantly in nucleoli. Clinical and pathological malignancy was strongly correlated with high nuclear and nucleolar CK2α expression. Recurrence-free survival was significantly reduced in patients with positive nucleolar CK2α staining (n=41; median 7·89 years [IQR 4·86–8·86]), comparing with patients with negative nucleolar staining (n=71; median 8·89 years [7·87–9·79]; p