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Research Articles: Therapeutics, Targets, and Development

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

Departments of ¹ Medical Oncology and ² Pathology, VU University Medical Center, Amsterdam, the Netherlands

Requests for reprints: Giuseppe Giaccone, Division of Medical Oncology, Academic Hospital Vrije Universiteit, 1117 De Boelelaan, HV 1081 Amsterdam, the Netherlands. Phone: 31-20-4444352; Fax: 31-20-4444079. E-mail: g.giaccone{at}vumc.nl

Abstract

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 p16 (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 II 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. [Mol Cancer Ther 2006;5(11):2905–13]

Grant support: European Society for Medical Oncology Foundation (Lugano, Switzerland; B. Vischioni) and the Walter Bruckerhoff Stiftung (Zurich, Switzerland; J.A. Rodriguez).

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 5/22/06; revised 8/ 8/06; accepted 9/11/06.

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