Frequent overexpression of aurora B kinase, a novel drug target, in non-small cell lung carcinoma patients

被引:113
作者
Vischioni, Barbara
Oudejans, Joost J.
Vos, Wim
Rodriguez, Jose A.
Giaccone, Giuseppe
机构
[1] Vrije Univ Amsterdam, Dept Med Oncol, Med Ctr, Amsterdam, Netherlands
[2] Vrije Univ Amsterdam, Dept Pathol, Med Ctr, Amsterdam, Netherlands
关键词
D O I
10.1158/1535-7163.MCT-06-0301
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The serine/threonine protein kinase aurora B, a key regulator of mitosis, is emerging as a novel drug target for cancer treatment. Aurora B overexpression has been previously documented by immunohistochemistry in several types of human tumors. We assessed aurora B expression in a series of 160 non-small cell lung cancer (NSCLC) samples (60% stage I, 21 % stage II, 11% stage III, and 8% stage IV). In addition, we determined the expression of survivin and p16, two molecules also involved in cell cycle control. Aurora B was expressed selectively in tumor cells compared with normal epithelium. Aurora B expression was significantly correlated with expression of survivin in the nucleus (P < 0.0001), but not with expression of p 16 (P = 0.134). High aurora B expression levels were significantly associated with older age (P = 0.012), male sex (P = 0.013), squamous cell carcinoma histology (P = 0.001), poor tumor differentiation grade (P = 0.007), and lymph node invasion (P = 0.037), in the subset of radically resected patients in our series. In addition, aurora B expression predicted shorter survival for the patients with adenocarcinoma histology, at both univariate (P = 0.020) and multivariate (P = 0.012) analysis. Survivin expression levels were neither associated with patient clinicopathologic characteristics nor with survival. However, expression of survivin in the nucleus was preferentially detected in stage I and 11 than in stage III and IV (P = 0.007) in the overall series of NSCLC samples. Taken together, our results suggest that aurora B may represent a valid target in NSCLC.
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页码:2905 / 2913
页数:9
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