Clinical Research Papers:

High casein kinase 1 epsilon levels are correlated with better prognosis in subsets of patients with breast cancer

Jose Luis Lopez-Guerra, Eva M. Verdugo-Sivianes, Daniel Otero-Albiol, Begoña Vieites, Maria J. Ortiz-Gordillo, Jose M. De León, Juan M. Praena-Fernandez, Juan J. Marin and Amancio Carnero _

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Oncotarget. 2015; 6:30343-30356. https://doi.org/10.18632/oncotarget.4850

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Jose Luis Lopez-Guerra1,2, Eva M. Verdugo-Sivianes1, Daniel Otero-Albiol1, Begoña Vieites3, Maria J. Ortiz-Gordillo2, Jose M. De León4, Juan M. Praena-Fernandez5, Juan J. Marin1,6 and Amancio Carnero1,7

1 Instituto de Biomedicina de Sevilla (IBIS/HUVR/CSIC/Universidad de Sevilla), Seville, Spain

2 Department of Radiation Oncology, University Hospital Virgen del Rocío, Seville, Spain

3 Department of Pathology, University Hospital Virgen Del Rocío, Seville, Spain

4 Unidad Funcional de Patología Mamaria, University Hospital Virgen Del Rocío, Seville, Spain

5 Methodology Unit- Fundación Pública Andaluza para la Gestión de la Investigación en Salud de Sevilla, Virgen del Rocío University Hospital, Seville, Spain

6 Department of Preventive Medicine and Public Health, Seville University, Seville, Spain

7 Consejo Superior de Investigaciones Científicas, Seville, Spain

Correspondence to:

Amancio Carnero, email:

Keywords: breast cancer, casein kinase 1 epsilon (CK1ε), relapse, disease-free survival, outcome

Received: May 18, 2015 Accepted: June 28, 2015 Published: July 13, 2015


Reliable biological markers that predict breast cancer (BC) outcomes after multidisciplinary therapy have not been fully elucidated. We investigated the association between casein kinase 1 epsilon (CK1ε) and the risk of recurrence in patients with BC. Using 168 available tumor samples from patients with BC treated with surgery +/- chemo(radio)therapy, we scored the CK1ε expression as high (≥1.5) or low (<1.5) using an immunohistochemical method. Kaplan-Meier analysis was performed to assess the risk of relapse, and Cox proportional hazards analyses were utilized to evaluate the effect of CK1ε expression on this risk. The median age at diagnosis was 60 years (range 35-96). A total of 58% of the patients underwent breast conservation surgery, while 42% underwent mastectomy. Adjuvant chemotherapy and radiation therapy were administered in 101 (60%) and 137 cases (82%), respectively. Relapse was observed in 24 patients (14%). Multivariate analysis found high expression of CK1ε to be associated with a statistically significant higher disease-free survival (DFS) in BC patients with wild-type p53 (Hazard ratio [HR] = 0.33; 95% CI, 0.12-0.91; P = 0.018) or poor histological differentiation ([HR] = 0.34; 95% CI, 0.12-0.94; P = 0.039) or in those without adjuvant chemotherapy ([HR] = 0.11; 95% CI, 0.01-0.97; P = 0.006). Our data indicate that CK1ε expression is associated with DFS in BC patients with wild-type p53 or poor histological differentiation or in those without adjuvant chemotherapy and thus may serve as a predictor of recurrence in these subsets of patients.

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