Department of Biomolecular Sciences, Fukushima Medical University School of Medicine, Fukushima, Japan.
Department of Diagnostic Pathology, Fukushima Medical University School of Medicine, Fukushima, Japan.
Cancer Sci. 2021 Feb;112(2):619-628. doi: 10.1111/cas.14728. Epub 2021 Jan 13.
Overexpression of the ubiquitous protein kinase, CK2α, has been reported in various human cancers. Here, we demonstrate that nuclear and nucleolar CK2α localization in invasive ductal carcinomas of the breast is a reliable predictor of poor prognosis. Cellular localization of CK2α in nuclei and nucleoli was analyzed immunohistochemically using surgical tissue blocks from 112 patients, who had undergone surgery without neoadjuvant chemotherapy. Clinical data collection and median follow-up period were for more than 5 y. In total, 93.8% of patients demonstrated elevated CK2α expression in nuclei and 36.6% of them displayed elevated expression predominantly in nucleoli. Clinicopathological malignancy was strongly correlated with elevated nuclear and nucleolar CK2α expression. Recurrence-free survival was significantly worse (P = .0002) in patients with positive nucleolar CK2α staining. The 5-y survival rate decreased to a roughly 50% in nucleolar CK2α-positive patients of triple-negative (P = .0069) and p Stage 3 (P = .0073) groups. In contrast, no patients relapsed or died in the triple-negative group who exhibited a lack of nucleolar CK2α staining. Evaluation of nucleolar CK2α staining showed a high secondary index with a hazard ratio of 6.629 (P = .001), following lymph node metastasis with a hazard ratio of 14.30 (P = .0008). Multivariate analysis demonstrated that nucleolar CK2α is an independent factor for recurrence-free survival. Therefore, we propose that histochemical evaluation of nucleolar CK2α-positive staining may be a new and robust prognostic indicator for patients who need further treatment. Functional consequences of nucleolar CK2 dysfunction may be a starting point to facilitate development of novel treatments for invasive breast carcinoma.
普遍存在的蛋白激酶 CK2α 的过表达已在各种人类癌症中被报道。在这里，我们证明了核和核仁 CK2α 在乳腺浸润性导管癌中的定位是预后不良的可靠预测指标。使用 112 名接受过无新辅助化疗手术的患者的手术组织块，通过免疫组织化学分析 CK2α 在细胞核和核仁中的细胞定位。收集临床数据并进行中位随访时间超过 5 年。总共，93.8%的患者在细胞核中表现出 CK2α 的升高表达，其中 36.6%的患者表现出主要在核仁中升高的表达。临床病理学恶性与核和核仁 CK2α 表达升高强烈相关。核仁 CK2α 阳性患者的无复发生存明显更差（P=0.0002）。核仁 CK2α 阳性的三阴性（P=0.0069）和 p 期 3 期（P=0.0073）患者的 5 年生存率下降到约 50%。相比之下，在三阴性组中，缺乏核仁 CK2α 染色的患者无一例复发或死亡。核仁 CK2α 染色的评估显示出较高的次要指数，风险比为 6.629（P=0.001），紧随淋巴结转移的风险比为 14.30（P=0.0008）。多变量分析表明，核仁 CK2α 是无复发生存的独立因素。因此，我们提出核仁 CK2α 阳性染色的组织化学评估可能是需要进一步治疗的患者的新的强大预后指标。核仁 CK2 功能障碍的功能后果可能是为侵袭性乳腺癌开发新治疗方法的起点。
