Anatomic Pathology, Moffitt Cancer Center, Tampa, FL 33612, USA.
Am J Clin Pathol. 2011 Jul;136(1):60-6. doi: 10.1309/AJCP2JJGYNIUAS2V.
IκB kinase (IKKε) is a serine/threonine protein kinase that belongs to the IKK kinase family. Recent studies have shown that IKKε functions as a breast and ovarian cancer oncogene. We demonstrated frequent overexpression of IKKε in pancreatic ductal adenocarcinoma (PDA). We immunohistochemically evaluated 78 PDAs using the avidin-biotin-peroxidase method and the anti-IKKε rabbit polyclonal antibody. Elevated IKKε reactivity (immunohistochemical score, 4-9) was observed in 64% of PDAs (50/78), but in 0.0% of nonneoplastic pancreatic ductal epithelium (0/113; P < .001). Kaplan-Meier analysis of overall survival revealed that patients with high IKKε-immunohistochemical scores (4-9) had significantly shorter survival than did patients with low IKKε immunohistochemical scores (0-3; P = .023; log-rank test) independent of tumor stage or grade. These data indicate that deregulation of IKKε is a common event in PDA and might have an important role in the pathogenesis of this deadly disease. In addition, IKKε could serve as a prognostic marker and potential therapeutic target for PDA intervention.
IKK 激酶(IKKε)是一种丝氨酸/苏氨酸蛋白激酶,属于 IKK 激酶家族。最近的研究表明,IKKε 作为乳腺癌和卵巢癌的致癌基因发挥作用。我们证明了 IKKε 在胰腺导管腺癌(PDA)中频繁过表达。我们使用亲和素-生物素-过氧化物酶法和抗 IKKε 兔多克隆抗体,对 78 例 PDA 进行了免疫组织化学评估。在 64%的 PDA(50/78)中观察到 IKKε 反应性升高(免疫组织化学评分 4-9),但在 0.0%的非肿瘤性胰腺导管上皮中(0/113;P<0.001)未观察到。总生存的 Kaplan-Meier 分析显示,高 IKKε 免疫组织化学评分(4-9)的患者的生存时间明显短于低 IKKε 免疫组织化学评分(0-3)的患者(P=0.023;log-rank 检验),与肿瘤分期或分级无关。这些数据表明,IKKε 的失调是 PDA 的常见事件,可能在这种致命疾病的发病机制中发挥重要作用。此外,IKKε 可以作为 PDA 干预的预后标志物和潜在的治疗靶点。