Abstract 4551: Prognostic impact of GLUT-1 and Ki-67 expressions in early-stage lung adenocarcinomas
Authors: Yuho Maki, Shinichi Toyooka, Koichi Ichimura, Junichi Soh, Kazuhiko Shien, Masashi Furukawa, Takayuki Muraoka, Norimitsu Tanaka, Tsuyoshi Ueno, Hiromasa Yamamoto, Hiroaki Asano, Kazunori Tsukuda, Masomi Yamane, Takahiro Oto, Shinichiro Miyoshi
Journal: Cancer Research (2012)

Abstract Background: Adenocarcinoma (AD) is the most common histology of non-small cell lung cancer (NSCLC). Five-year disease-free survival rates (5-DFS) remain 80% for stage IA lung AD at best, and it is clinically required to identify biomarkers that can predict clinical outcome in the patients with early stage ADs. The glucose transporter isoform 1 (GLUT-1), that is one of the glucose transporter (GLUT) family, is expressed in most types of cells with metabolic change caused by hypoxia. The Ki-67 protein is known as maker of proliferation. Overexpressions of GLUT-1 and Ki-67 are knouwn as prognostic marker in many types of cancers. We determined the expression levels of GLUT-1 and Ki-67 to evaluate the impact of these alterations on the clinical outcome in early stage lung AD. Materials and Methods: We reviewed 105 patients with stage IA lung AD who underwent complete resection at our institute between January 2004 and December 2006. Expressions of GLUT-1 and Ki-67 were evaluated by Immunohistochemistry. The GLUT-1 expression was considered positive if the percentage of tumor cells staining was more than 10%. The Ki-67 staining was evaluated by the labeling index, and was considered positive when the labeling index was more than 15%. The significance of the differences between two groups was determined using the chi-square test. The 5-DFS and 5-year overall survival (5-OS) were evaluated by Kaplan-Meier analysis. Results: GLUT-1 and Ki-67 expressions were positive in 12 (11.4%) and 33 (31.4%) out of 105 patients, respectively. High GLUT-1 expression is significantly frequent in male (P=0.005), ever-smoker (P=0.005), and tumors with more than 2 cm at maximum diameter (P=0.033), and high Ki-67 expression is significantly frequent in male (P&amp;lt;0.001) ever-smoker (P=0.005), and tumors without predominance of lipidic component (new lung adenocarcinoma criteria: JTO 2011)(P=0.006). Positive expressions of GLUT-1 and Ki-67 were correlated with each other (P =0.002). The 5-OS and 5-DFS rates of all 105 patients were 94.6% and 90.2%, respectively. The 5-DFS rates in the GLUT-1 and Ki-67 positive patients were significantly poorer than that of GLUT-1 and Ki-67 negative patients, respectively (45.6% vs. 96.2% in GLUT-1; P &amp;lt; 0.001) (71.7% vs. 98.3% in Ki-67; P &amp;lt; 0.001). Male sex and smoking history were also significantly associated with the poor DFS. A multivariate analysis revealed that positive expressions of GLUT-1 (Hazard ratio [HR]: 0.14, P = 0.009) and Ki-67 (HR: 0.19, P = 0.046) independently associated with poor clinical outcome. Conclusion: High GLUT-1 and Ki-67 expressions are present in larger or lipidic non-predominant lung adenocaricinomas, respectively, and they can independently predict clinical outcome of patients with early stage lung adenocarcinomas. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4551. doi:1538-7445.AM2012-4551