Ogawa Eiji, Takenaka Kazumasa, Katakura Hiromichi, Adachi Masashi, Otake Yosuke, Toda Yoshinobu, Kotani Hirokazu, Manabe Toshiaki, Wada Hiromi, Tanaka Fumihiro
Department of Thoracic Surgery, Faculty of Medicine, Kyoto University, Kyoto, Japan.
Ann Surg Oncol. 2008 Feb;15(2):547-54. doi: 10.1245/s10434-007-9653-8. Epub 2007 Nov 28.
Aurora-A, also known as STK15/BTAK, is a member of the protein serine/threonine kinase family, and experimental studies have revealed that Aurora-A plays critical roles in cell mitosis and in carcinogenesis. However, no clinical studies on Aurora-A expression in non-small-cell lung cancer (NSCLC) have been reported. Thus, the present study was conducted to assess the clinical significance of Aurora-A status.
A total of 189 consecutive patients with resected pathologic (p-)stage I-IIIA, NSCLC were retrospectively reviewed, and immunohistochemical staining was used to detect Aurora-A expression.
Aurora-A expression was negative in 31 patients (16.4%); among Aurora-A positive patients, 124 patients showed pure diffuse cytoplasmic Aurora-A expression and the other 34 patients showed perimembrane Aurora-A expression. Perimembrane Aurora-A tumors showed the highest proliferative index (PI) (mean PIs for negative, diffuse cytoplasmic, and perimembrane tumors: 49.2, 41.7, and 63.5, respectively; P < .001). Five-year survival rates of Aurora-A negative, diffuse cytoplasmic, and perimembrane patients were 67.8%, 66.7%, and 47.6%, respectively, showing the poorest postoperative survival in perimembrane patients (P = .033). Subset analyses revealed that perimembrane Aurora-A expression was a significant factor to predict a poor prognosis in squamous cell carcinoma patients, not in adenocarcinoma patients. A multivariate analysis confirmed that perimembrane Aurora-A expression was an independent and significant factor to predict a poor prognosis.
Perimembrane Aurora-A status was a significant factor to predict a poor prognosis in correlation with enhanced proliferative activity in NSCLC.
极光激酶A(Aurora-A),也被称为丝氨酸/苏氨酸激酶15(STK15)/乳腺癌肿瘤激酶(BTAK),是蛋白质丝氨酸/苏氨酸激酶家族的成员,实验研究表明,Aurora-A在细胞有丝分裂和致癌过程中起关键作用。然而,尚未有关于非小细胞肺癌(NSCLC)中Aurora-A表达的临床研究报道。因此,本研究旨在评估Aurora-A状态的临床意义。
回顾性分析了189例连续接受手术切除的病理分期为I-IIIA期的NSCLC患者,并采用免疫组织化学染色检测Aurora-A表达。
31例患者(16.4%)Aurora-A表达为阴性;在Aurora-A阳性患者中,124例表现为单纯弥漫性细胞质Aurora-A表达,另外34例表现为膜周Aurora-A表达。膜周Aurora-A肿瘤显示出最高的增殖指数(PI)(阴性肿瘤、弥漫性细胞质肿瘤和膜周肿瘤的平均PI分别为49.2、41.7和63.5;P <.001)。Aurora-A阴性、弥漫性细胞质和膜周患者的5年生存率分别为67.8%、66.7%和47.6%,膜周患者术后生存率最差(P =.033)。亚组分析显示,膜周Aurora-A表达是预测鳞状细胞癌患者预后不良的重要因素,而不是腺癌患者。多因素分析证实,膜周Aurora-A表达是预测预后不良的独立且重要的因素。
膜周Aurora-A状态是预测NSCLC预后不良的重要因素,与增殖活性增强相关。