Lopez-Guerra Jose Luis, Verdugo-Sivianes Eva M, Otero-Albiol Daniel, Vieites Begoña, Ortiz-Gordillo Maria J, De León Jose M, Praena-Fernandez Juan M, Marin Juan J, Carnero Amancio
Instituto de Biomedicina de Sevilla (IBIS/HUVR/CSIC/Universidad de Sevilla), Seville, Spain.
Department of Radiation Oncology, University Hospital Virgen del Rocío, Seville, Spain.
Oncotarget. 2015 Oct 6;6(30):30343-56. doi: 10.18632/oncotarget.4850.
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.
能够预测多学科治疗后乳腺癌(BC)预后的可靠生物标志物尚未完全阐明。我们研究了酪蛋白激酶1ε(CK1ε)与BC患者复发风险之间的关联。我们使用免疫组织化学方法,对168例接受手术±化疗(放疗)的BC患者的可用肿瘤样本进行评分,将CK1ε表达分为高(≥1.5)或低(<1.5)。采用Kaplan-Meier分析评估复发风险,并利用Cox比例风险分析评估CK1ε表达对该风险的影响。诊断时的中位年龄为60岁(范围35 - 96岁)。共有58%的患者接受了保乳手术,42%的患者接受了乳房切除术。分别有101例(60%)和137例(82%)患者接受了辅助化疗和放疗。24例患者(14%)出现复发。多变量分析发现,在野生型p53的BC患者(风险比[HR]=0.33;95%置信区间,0.12 - 0.91;P = 0.018)、组织学分化差的患者([HR]=0.34;95%置信区间,0.12 - 0.94;P = 0.039)或未接受辅助化疗的患者([HR]=0.11;95%置信区间,0.01 - 0.97;P = 0.006)中,CK1ε高表达与无病生存期(DFS)显著相关。我们的数据表明,CK1ε表达与野生型p53、组织学分化差或未接受辅助化疗的BC患者的DFS相关,因此可能作为这些患者亚组复发的预测指标。