CHFR expression is preferentially impaired in smoking-related squamous cell carcinoma of the lung, and the diminished expression significantly harms outcomes
Masafumi Takeshita
Division of Pathophysiological and Experimental Pathology, Department of Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Search for more papers by this authorCorresponding Author
Takaomi Koga
Division of Pathophysiological and Experimental Pathology, Department of Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Fax: +81-92-642-5965
Division of Pathophysiological and Experimental Pathology, Department of Pathology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, JapanSearch for more papers by this authorKoichi Takayama
Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Search for more papers by this authorHidenori Kouso
Division of Pathophysiological and Experimental Pathology, Department of Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Search for more papers by this authorYuko Nishimura-Ikeda
Division of Pathophysiological and Experimental Pathology, Department of Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Search for more papers by this authorIchiro Yoshino
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Search for more papers by this authorYoshihiko Maehara
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Search for more papers by this authorYoichi Nakanishi
Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Search for more papers by this authorKatsuo Sueishi
Division of Pathophysiological and Experimental Pathology, Department of Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Search for more papers by this authorMasafumi Takeshita
Division of Pathophysiological and Experimental Pathology, Department of Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Search for more papers by this authorCorresponding Author
Takaomi Koga
Division of Pathophysiological and Experimental Pathology, Department of Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Fax: +81-92-642-5965
Division of Pathophysiological and Experimental Pathology, Department of Pathology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, JapanSearch for more papers by this authorKoichi Takayama
Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Search for more papers by this authorHidenori Kouso
Division of Pathophysiological and Experimental Pathology, Department of Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Search for more papers by this authorYuko Nishimura-Ikeda
Division of Pathophysiological and Experimental Pathology, Department of Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Search for more papers by this authorIchiro Yoshino
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Search for more papers by this authorYoshihiko Maehara
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Search for more papers by this authorYoichi Nakanishi
Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Search for more papers by this authorKatsuo Sueishi
Division of Pathophysiological and Experimental Pathology, Department of Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Search for more papers by this authorAbstract
Loss of tumor suppressors and activation of oncogenes lead to carcinogenesis. Abnormal expression of CHFR, a novel checkpoint gene, or of Aurora kinases, key regulators of mitosis, has been detected in a variety of solid tumors. Recently, CHFR has been revealed to ensure chromosomal stability by controlling the expression level of Aurora-A in vitro. However, the frequency of aberrant expression of these proteins and the association with clinicopathologic parameters remain poorly defined in nonsmall-cell lung cancer (NSCLC). In this study, we investigated the immunohistochemical protein expression of CHFR and Aurora-A in 157 NSCLC cases and evaluated the association between clinicopathologic parameters statistically. The relationship between CHFR protein and mRNA levels and the association between this relationship and promoter methylation of the CHFR gene were also examined in 20 frozen sections of NSCLC. Overexpression of Aurora-A and reduced expression of CHFR were found in 94 cases (59.8%) and 62 cases (39%) of NSCLC, respectively, and those were significantly correlated with tumor differentiation and size. Moreover, diminished CHFR expression was significantly associated with smoking-related squamous cell carcinoma cases and poor prognosis. Multivariate analysis revealed that CHFR expression was an independent prognostic factor. A statistical correlation was evident between CHFR protein and mRNA expression. In conclusion, our results suggest the aberrant expression of Aurora-A and/or of CHFR contributed to the increase in the malignant potential of NSCLC. We also revealed that CHFR expression was predominantly impaired in smoking-related squamous cell carcinoma and might be a useful prognostic marker in NSCLC. © 2008 Wiley-Liss, Inc.
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