Impact of GLUT1 and Ki-67 expression on early‑stage lung adenocarcinoma diagnosed according to a new international multidisciplinary classification

Maki,Yuho; Soh,Junichi; Ichimura,Kouichi; Shien,Kazuhiko; Furukawa,Masashi; Muraoka,Takayuki; Tanaka,Norimitsu; Ueno,Tsuyoshi; Yamamoto,Hiromasa; Asano,Hiroaki; Tsukuda,Kazunori; Toyooka,Shinichi; Miyoshi,Shinichiro

doi:10.3892/or.2012.2087

Impact of GLUT1 and Ki-67 expression on early‑stage lung adenocarcinoma diagnosed according to a new international multidisciplinary classification

Authors:
- Yuho Maki
- Junichi Soh
- Kouichi Ichimura
- Kazuhiko Shien
- Masashi Furukawa
- Takayuki Muraoka
- Norimitsu Tanaka
- Tsuyoshi Ueno
- Hiromasa Yamamoto
- Hiroaki Asano
- Kazunori Tsukuda
- Shinichi Toyooka
- Shinichiro Miyoshi
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Affiliations: Department of Thoracic Surgery, Okayama University Hospital, Okayama, Japan, Department of Pathology, Okayama University Hospital, Okayama, Japan
Published online on: October 17, 2012 https://doi.org/10.3892/or.2012.2087
Pages: 133-140

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Abstract

High expression levels of glucose transporter isoform 1 (GLUT1) and Ki-67 are reportedly associated with malignancy-related clinicopathological factors in malignant tumors. Recently, a new histological IASLC/ATS/ERS classification for lung adenocarcinoma was proposed. In this study, we investigated the clinicopathological impact of GLUT1 and Ki-67 expression on early-stage lung adenocarcinoma classified according to the IASLC/ATS/ERS classification. One hundred and five patients with completely resected stage IA lung adenocarcinoma were retrospectively classified into two groups, a ʻnon-invasive typeʼ (n=31) or an ʻinvasive typeʼ (n=74), based on the IASLC/ATS/ERS classification. GLUT1 and Ki-67 expression status was evaluated using immunohistochemistry. The epidermal growth factor receptor (EGFR) and KRAS mutation status was determined using PCR-based assays. Positive GLUT1 and Ki-67 expression and EGFR and KRAS mutations were detected in 28 (27%), 33 (31%), 51 (49%) and 5 (8%) cases, respectively. Positive GLUT1 expression was significantly associated with a wild-type EGFR and mutant KRAS status. A multivariate analysis revealed that positive GLUT1 expression was independently associated with the ʻinvasive typeʼ. In multivariate analyses for overall survival (OS) and disease-free survival (DFS), positive Ki-67 and GLUT1 expression was the only independent factor for a poor OS (P=0.012) and DFS (P=0.040), respectively. In addition, when stratified according to the GLUT1 and Ki-67 status, double-positive cases had the poorest DFS and OS times, compared with the other categories. Positive GLUT1 expression is associated with the invasive character of early-stage lung adenocarcinoma and with early disease relapse. Our results strongly suggest that GLUT1 and Ki-67 play important roles in acquiring biological malignant potential in early-stage lung adenocarcinoma.

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